Culture

BIRMINGHAM, Ala. - University of Alabama at Birmingham researchers have added fresh evidence that early exposure to vaccine-, bacterial- or microbiota-derived antigens has a dramatic effect on the diversity of antibodies an adult mammal will have to fight future infections by pathogens. This antibody diversity is called the clonal repertoire -- basically different single cells with distinct antibody potential that can multiply into a large clone of cells, all producing that distinct antibody.

In a mouse study published in the journal Immunity, they looked at a group of immune cells called B-1 B cells. Although all B cells have the ability to develop into antibody-secreting cells to control pathogens, innate-like B-1 B cells originate from a developmental program that is distinct from conventional B cells.

The UAB researchers, led by first author J. Stewart New, Ph.D., and co-senior authors John Kearney, Ph.D., and R. Glenn King, Ph.D., UAB Department of Microbiology, looked at a subset of B-1 B cells that react to N-acetyl-D-glucosamine-containing Lancefield Group A carbohydrate, or GAC, a cell wall polysaccharide of the bacterial pathogen Streptococcus pyogenes.

They asked the question, how much will clonal diversity differ in mice grown under sterile germ-free conditions, versus mice with a normal gut microbiota from birth, or mice with a normal microbiota that are also vaccinated as neonates with GAC-bearing S. pyogenes. To answer, they sequenced the immunoglobulin heavy chain variable region, or IGHV region, for single B cells labeled with GAC. Single-cell sequencing has exploded in the past decade as a powerful research tool that takes biology to a new depth of understanding.

New, Kearney, King and colleagues found that environmental antigen-dependent selection events play a significant role to shape the GAC-reactive B-1 B cell clonal repertoire. New is a postdoctoral fellow, Kearney is a professor, and King is assistant professor of microbiology in the UAB School of Medicine.

In general, germ-free mice had a low IGHV clonal diversity, while both conventional mice and neonatal-vaccination mice had high clonal diversities. However, the conventional and neonatal-vaccination mice differed. Both showed that the establishment of IGHV region 6-3 GAC-reactive B cell clonal dominance was microbiota-dependent; but in addition, the neonatal immunization with S. pyogenes expanded the typically minor IGHV region 7-3 GAC-reactive clonotypes, compared to those clonotypes in the conventional mice.

The researchers found that colonization of adult germ-free mice promoted N-acetyl-D-glucosamine-reactive B-1 B cell development and led to clonally related immunoglobulin A-positive plasma cells in the small intestine. Plasma cells differentiate from B cells, and they are the ones that produce antibody. Immunoglobulin A secretion in the gut is beneficial because it helps constrain the composition and inflammatory activity of the normal microbiota in the small intestine.

Kearney says that understanding how exposure to microbial antigens in early life determines the clonality and ensuing antibody responses of the B-1 B cell repertoire has implications for vaccination approaches and schedules.

B-1 B cells also are known to produce natural immunoglobulin M. Deficiencies of immunoglobulin M have been associated with increased rates of autoimmunity and allergic diseases. The dramatic effect of early exposure to vaccine or bacteria for clonal diversity seen in the current research, Kearney said, "may provide an alternative mechanistic explanation for the influence of environmental antigens on the allergic and autoimmune disease susceptibility, which is often discussed in context of the hygiene hypothesis."

The hygiene hypothesis suggests that a reduction in infections in Western countries -- due to better hygiene -- has led to an increase in autoimmune and allergic diseases.

A study from Ann & Robert H. Lurie Children's Hospital of Chicago found that children with a MED-EL Synchrony cochlear implant device can undergo MRI safely, with no discomfort and reduced need for sedation or anesthesia. Findings were published in the peer-reviewed journal Laryngoscope.

Cochlear implants allow people who are deaf to hear, and they contain a small magnet that is used to attach an external sound processor behind the ear. In most implant designs, the magnet had to be surgically removed before an MRI could be performed, and surgically replaced after the scan, because an MRI scanner also contains a powerful magnet. A later strategy to avoid magnet removal used a special head wrap to counteract the force on the cochlear implant magnet from the MRI. However, patients would still report feeling uncomfortable pressure or pain during the MRI, which often produced anxiety. The latest cochlear implant from MED-EL incorporates a revolutionary design change that allows the special internal magnet to rotate with the magnetic force from the MRI, making surgical removal of the magnet or a head wrap unnecessary. The greater safety and comfort level increases MRI access for children with MED-EL Synchrony cochlear implant devices.

"MRI is an increasingly important diagnostic tool, and access to MRI evaluation without pain and other complications is critical for children with cochlear implants," says lead author Nancy Young, MD, Medical Director of Audiology & Cochlear Implant Programs at Lurie Children's and Professor of Pediatric Otolaryngology at Northwestern University Feinberg School of Medicine. "Few children in our study required sedation or anesthesia during MRI, and none because they had an implant. In the past, all of our patients with cochlear implants required sedation during scanning, to avoid additional surgery to remove the magnet. This is a huge improvement, especially for children with conditions requiring repeated imaging."

The study included seven patients (ages 1.3 to 19 years) with MED-EL Synchrony cochlear implant devices, who underwent 17 episodes of 1.5 or 3.0 Tesla MRI. Seventy-six percent of MRI sessions were completed in awake patients. No patients had device-related discomfort and no magnet related complications occurred. Ninety-three percent of brain studies (13 of 14) and all body studies provided clinically useful diagnostic imaging.

To date, Lurie Children's has implanted 208 children with the MED-EL Synchrony cochlear device since it became available in 2015. More than 2000 cochlear implant surgeries have been done at Lurie Children's since the program began in 1991.

Scientists from the Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan (USask) and Temple University (Philadelphia, U.S.) have demonstrated that a Salmonella biofilm protein can cause autoimmune responses and arthritis in animals.

Salmonella was previously thought to only form biofilms in the environment, such as on food processing surfaces. Biofilms are dense collections of bacteria that stick together on surfaces to protect the bacteria from harsh conditions, including antibiotics and disinfectants. Detecting biofilms in an animal during an infection was a surprise.

In research published today in PLOS Pathogens, a VIDO-InterVac team led by Aaron White discovered that Salmonella biofilms were formed in the intestines of infected mice. For the study, the team used a mouse model to replicate human food-borne illness and showed that a biofilm protein called "curli" that grows on the surface of bacteria was connected to negative health outcomes.

Curli are a special type of protein called amyloids. Similar human proteins have been associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Scientists don't know how these diseases start, but have speculated that something must "trigger" the accumulation of amyloids.

"We are the first to show that a food-borne pathogen can make these types of proteins in the gut," said White, a leading expert on Salmonella biofilms and curli amyloids.

"There has been speculation that bacteria can stimulate amyloid plaque formation in Alzheimer's, Parkinson's and ALS and contribute to disease progression. The discovery of curli in the gut could represent an important link, pointing to a potentially infectious cause for these diseases."

Collaborator Çagla Tükel and her team from Temple University determined that the presence of curli led to autoimmunity and arthritis--two conditions that are known complications of Salmonella infections in humans.

"In mice, these reactions were triggered within six weeks of infection, demonstrating that curli can be a major driver of autoimmune responses," said Tükel.

The next step in the research is to confirm that this also occurs in humans, and test if other food-borne pathogens related to Salmonella can cause similar autoimmune reactions.

"This important discovery suggests that food-borne pathogens could initiate or worsen autoimmunity and have the potential to contribute to amyloid disorders such as Alzheimer's and Parkinson's disease," said VIDO-InterVac Director Dr. Volker Gerdts.

The news about remdesivir, the investigational anti-viral drug that has shown early promise in the fight against COVID-19, keeps getting better.

This week researchers at Vanderbilt University Medical Center (VUMC), the University of North Carolina at Chapel Hill and Gilead Sciences reported that remdesivir potently inhibited SARS-CoV-2, the virus which causes COVID-19, in human lung cell cultures and that it improved lung function in mice infected with the virus.

These preclinical findings help explain the clinical effect the drug has had in treating COVID-19 patients. Remdesivir has been given to patients hospitalized with COVID-19 on a compassionate use basis since late January and through clinical trials since February.

In April, a preliminary report from the multicenter Adaptive COVID-19 Treatment Trial (which included VUMC) suggested that patients who received the drug recovered more quickly.

"All of the results with remdesivir have been very encouraging, even more so than we would have hoped, but it is still investigational, so it was important to directly demonstrate its activity against SARS-CoV-2 in the lab and in an animal model of disease," said VUMC's Andrea Pruijssers, PhD.

Pruijssers, research assistant professor of Pediatrics at VUMC and lead antiviral scientist in the laboratory of Mark Denison, MD, is the paper's co-corresponding author with Timothy Sheahan, PhD, assistant professor of Epidemiology at UNC-Chapel Hill.

Denison, the E.C. Stahlman Professor of Pediatrics at VUMC, directs the Division of Pediatric Infectious Diseases. He and Ralph Baric, PhD, the William R. Kenan, Jr. Distinguished Professor of Epidemiology at UNC-Chapel Hill, and colleagues have been studying remdesivir since 2014.

They were the first to perform detailed studies to demonstrate that the drug, which was developed by Gilead Sciences to combat hepatitis C and respiratory syncytial virus, and later the Ebola virus, also showed broad and highly potent activity against coronaviruses in laboratory tests.

The current findings, reported this week in the journal Cell Reports, provide "the first rigorous demonstration of potent inhibition of SARS-CoV-2 in continuous and primary human lung cultures." The study is also the first to suggest that remdesivir can block the virus in a mouse model.

Ongoing clinical trials will determine precisely how much it benefits patients in different stages of COVID-19 disease.

Meanwhile in the laboratory, Pruijssers said, "We also are focusing on how to use remdesivir and other drugs in combinations to increase their effectiveness during COVID-19 and to be able to treat at different times of infection."

COVID-19, which to date has infected more then 12 million people and killed nearly 600,000 worldwide, is at least the third instance since 2003 in which a coronavirus originally transmitted from bats has caused serious illness in humans.

Thus there is an urgent need to identify and evaluate broadly efficacious and robust therapies that can limit and prevent coronavirus infections. "Broad-spectrum antiviral drugs, antibodies, and vaccines are needed to combat the current pandemic and those that will emerge in the future," the researchers said.

In addition to SARS-CoV-2, studies in the Denison and Baric labs have shown that remdesivir is effective against a vast array of coronaviruses, including other bat viruses that could emerge in the future in humans.

"We hope that will never happen, but just as we were working to characterize remdesivir over the past six years to be ready for a virus like SARS-CoV-2, we are working and investing now to prepare for any future coronavirus," Denison said. "We want remdesivir and other drugs to be useful both now and in the future."

ITHACA, N.Y. - The costs of implementing food safety practices to prevent foodborne illnesses have been viewed as a threat to the financial well-being of small farms, which must pay a higher percentage of their annual sales than larger farms to meet safety standards. But a new Cornell University study finds that when small-scale farmers are trained in food safety protocols and develop a farm food safety plan, new markets open up to them, leading to an overall gain in revenue.

"Our results should be welcomed by growers in understanding that food safety investments can support both reduced microbial risks and sales growth," said Todd Schmit, associate professor in the Charles H. Dyson School of Applied Economics and Management.

Schmit is lead author of "Assessing the Costs and Returns of On-farm Food Safety Improvements: A Survey of Good Agricultural Practices (GAPs) Training Participants," which published in the journal PLOS ONE.

"The study highlights the value of food safety to all farmers," said study co-author Elizabeth Bihn, director of the Cornell-based National Good Agricultural Practices (GAPs) Program and the Produce Safety Alliance, a collaborative project between Cornell, the U.S. Department of Agriculture and the U.S. Food and Drug Administration (FDA). "It's great to know that by investing in food safety, you are actually getting a market benefit."

In 1998, the FDA released a guide for good agricultural practices, to minimize microbial food safety hazards for fresh fruits and vegetables. Though the recommendations for farmers were voluntary, many buyers - including grocery stores and wholesale buyers, farm-to-school programs and food distributors - demanded growers follow GAPs guidelines as a requisite for doing business. For verification, buyers commonly request that growers get a third-party audit.

The National GAPs Program and Cornell Cooperative Extension began offering a multiday GAPs training program in 2008 to help growers create a farm food safety plan, a necessary step to passing an audit.

In the study, food scientists, extension educators and economists surveyed New York state farms that had previously participated in the GAPs trainings. Educators asked the farmers about costs of implementing GAPs, which can include washing stations, coolers and new employees to monitor and record food safety steps and actions. They also asked about the financial benefits.

"What we found is that, consistent with the literature," Schmit said, "the relative cost burden is higher for smaller-scale producers, but they also have more relative benefits of increasing sales to new markets and buyers."

In 2015, the FDA completed its Food Safety Modernization Act (FSMA) Produce Safety Rule, a set of specific actions growers must take to prevent contamination from foodborne pathogens. While GAPs certification is voluntary, market-driven and requires an audit, FSMA compliance is mandatory and farms receive inspections.

"It is important to note that markets drove food safety requirements before FSMA," Bihn said, "and will likely continue to drive markets given that FSMA exempts or excludes certain farms."

In the future the researchers hope to do similar types of surveys and analyses in other parts of the country, specific to the FSMA implementation.

AURORA, Colo. (July 9, 2020) - Researchers at the University of Colorado School of Medicine have identified how specific brain cells interacting during development could be related to neurological and neuropsychiatric diseases, including some that occur later in life.

Brain function depends on the precise formation of millions of connections between specific brain cell types, including neurons and glial cells. The scientists at CU studied how a type of connection, called myelination, functions between specific cell types and how the body's nervous system removes excess connections. Details of their research are outlined in an article published Monday, July 6, in the journal Nature Neuroscience.

"We believe these new data will lead to improved understanding of the potential causes for some neurological and neuropsychiatric diseases," said senior author Bruce Appel, PhD, professor and head of the Department of Pediatrics Section of Developmental Biology.

Appel and first author Alexandria N. Hughes, a graduate student in the CU Graduate School's Neuroscience Program, used larval zebrafish, small and transparent vertebrates that share many aspects of nervous system development with humans. Because zebrafish larvae are transparent, cells of the nervous system can be watched during the course of development.

The team found that microglia, which are the brain's population of immune cells that defend against infection throughout life, also play an essential role in regulating myelination. Myelination is a connection process formed between electrically active neurons and a glial cell type called oligodendrocytes. Oligodendrocytes wrap the long axons of neurons with segments of fatty myelin membrane to insulate them, which increases the speed brain signals are sent.

The process of how the nervous system removes incorrect myelin segments, or sheaths, is unknown.

In their study, the CU researchers observed that microglia extend within myelinated tracts of the nervous system and examine individual myelin sheaths, removing some of them by phagocytosis, or cellular "eating." Furthermore, the amount of myelin that microglia ate depended on neuronal activity, suggesting that microglia may listen to neurons to determine whether to remove myelin.

Understanding myelin is important because myelin abnormalities are a hallmark of numerous neurological and neuropsychiatric diseases, including Alzheimer's disease, schizophrenia, and autism spectrum disorder.

These newly reported data raise the possibility that microglial dysfunction, even early in development, could set the stage for later disease emergence and progression by altering myelination.

"Learning how microglia, oligodendrocytes, and neurons work together to build a functional nervous system could ultimately help our understanding of how these cells interact in diseases of development or aging and may influence strategies for myelin repair," Hughes said.

In a new study published in the leading international journal, Child Abuse and Neglect, University of South Australia researchers have found that by their mid-teens, children who were the subject of child protective services contact, are up to 52 per cent more likely to be hospitalised, for a range of problems, the most frequent being mental illness, toxic effects of drugs and physical injuries.

The world-first study examined the impact of child abuse and neglect from data covering 608,540 South Australian born children since1986.

Lead author and Research Fellow at UniSA, Dr Emmanuel Gnanamanickam says the research underlines the long-term impacts of child abuse and neglect and the importance of protecting children from an early age to prevent ongoing health problems.

"The research shows that, the system is identifying children who are at risk, but there is not enough happening to support these children and their families early and as they enter adulthood," Dr Gnanamanickam says.

The research found that by the age of 16.5 years, children who had at some time been placed in Out of Home Care (OOHC) had an average of 7.7 hospital admissions, about four times the mean of 2.0 for children who had never had contact with CPS.

And the impact continues beyond adolescence.

People aged between 15 and 32 years, who have had contact with CPS in their childhood, had two to four times more hospitalisations than those with no contact. Children with substantiated child abuse or neglect and had entered OOHC, were shown to be at the highest risk.

"The study indicates that there are long-term health and mental health consequences for children experiencing abuse and neglect and that those impacts are felt even by children whose cases are not elevated by the child protection system," Dr Gnanamanickam says.

"Rates of hospitalisation for children who are placed in out of home care, because these cases are the most serious, are highest, and further research is required to unpack how the elements of abuse and neglect interact with removal from family, to ensure the negative outcomes for these children can be mitigated as far as possible.

And the lead investigator of the iCAN (impacts of child abuse and neglect) project, Professor Leonie Segal says the key take home message from the research is that better access to high quality infant, child and adolescent mental health services must be a critical part of any effective intervention strategy.

"Differences in hospitalisation start in infancy, highlighting the need to pursue opportunities for preventing child maltreatment and protecting children from harm from an early age," Prof Segal says.

"Clearly more needs to be done to support troubled families and this is something that requires an integrated approach that would see child protection working with the wider human services sector to ensure that effective, cross-agency strategies are available from early in life.

"Not only is there an ethical imperative to improve the health and wellbeing of our most vulnerable children across the life course, doing better to address child maltreatment and prevent associated harms, presents a considerable hospitalisation prevention opportunity."

Glass is an immensely interesting archaeological material: While its fragility and beauty is fascinating in itself, geochemical studies of invisible tracers can reveal more than what meets the eye. In a new international collaboration study from the Danish National Research Foundation's Centre for Urban Network Evolutions (UrbNet), the Aarhus Geochemistry and Isotope Research Platform (AGiR) at Aarhus University and the Danish-German Jerash Northwest Quarter Project (Aarhus University and University of Münster), researchers have found a way to determine the origin of colourless glass from the Roman period. The study is published in Scientific Reports.

The Roman glass industry was prolific, producing wares for drinking and dining, window panes and coloured glass 'stones' for wall mosaics. One of its outstanding achievements was the production of large quantities of a colourless and clear glass, which was particularly favoured for high-quality cut drinking vessels. The fourth-century Price Edict of the emperor Diocletian refers to colourless glass as 'Alexandrian', indicating an origin in Egypt. However, large amounts of Roman glass are known to have been made in Palestine, where archaeologists have uncovered furnaces for colourless glass production. Such furnaces have not been uncovered in Egypt, and hitherto, it has been very challenging to scientifically tell the difference between glass made in the two regions.

Now, an international collaboration led by Assistant Professor Gry Barfod from UrbNet and AGiR at Aarhus University has found the solution. Their work on Roman glass from the Danish-German Jerash Northwest Quarter Project in Jordan shows that the isotopes of the rare element hafnium can be used to distinguish between Egyptian and Palestinian glass and provide compelling evidence that the prestigious colourless glass known as 'Alexandrian' was indeed made in Egypt. Two of the co-authors of the publication, Professor Achim Lichtenberger (University of Münster) and Centre Director at UrbNet Professor Rubina Raja, head the archaeological project in Jerash, Jordan. Since 2011, they have worked at the site and have furthered high-definition approaches to the archaeological material from their excavations. Through full quantification methods, they have over and again shown that such an approach is the way forward in archaeology, when combining it with in context studies of various material groups. The new study is yet another testament to this approach.

"Hafnium isotopes have proved to be an important tracer for the origins of sedimentary deposits in geology, so I expected this isotope system to fingerprint the sands used in glassmaking", states Gry Barfod. Professor at Aarhus University Charles Lesher, co-author of the publication, continues: "The fact that this expectation is borne out by the measurements is a testament of the intimate link between archaeology and geology."

Hafnium isotopes have not previously been used by archaeologists to look at the trade in ancient man-made materials such as ceramics and glass. Co-author Professor Ian Freestone, University College London, comments, "These exciting results clearly show the potential of hafnium isotopes in elucidating the origins of early materials. I predict they will become an important part of the scientific toolkit used in our investigation of the ancient economy."

Fact box:

The sand along the Mediterranean coast of Egypt and Levant (Palestine, Israel, Lebanon and Syria) originates from the Nile and is ideal for glass production because it naturally contains the amount of lime needed to keep the glass stable and not degradable. In the Levant, they made transparent glass by adding manganese - it was good, but not perfect. The second type of Roman glass, which scientists now show came from Egypt, the glassmakers made transparent by adding antimony (Sb), which made it crystal clear; therefore, this was the most valuable glass.

While access to nature is an established social determinant of health with clear benefits to physical, mental, and social health, it does not receive as must attention by health care providers or health systems as other social concerns, according to a new piece by a Penn Medicine physician published today in the American Journal of Preventive Medicine.

"I think changing how people interact with their neighborhood environment, and changing the environment directly, is perceived as being hard and, perhaps, out of bounds of what is possible from health care," said Eugenia South, MD, an assistant professor of Emergency Medicine "We don't learn about environmental contributors to health in medical school, and it is not part of traditional biomedical care," South said. "And yet, changing the neighborhood, including increasing nature access, has the potential to have a huge health impact on a lot of people. It is worth pursuing."

Social determinants of health are the social, economic, or political factors that affect people's lives and shape the health of individuals and their communities. These could include whether or not people have access to healthy food or stable housing, whether there are higher rates of violence in their communities, what physical infrastructure is in their neighborhood, and what job opportunities are available to them. Many of these factors tie back to recent national conversations about structural racism, and there has also been elevated attention, due at least in part to requirements set forth by the Affordable Care Act. This has led to interventions from health systems, such as through investment in affordable housing.

But access to nature and greenspace is often not given as much consideration when it comes to addressing the inequities that play into people's health. This is in face of a multitude of studies that show that time in -- and even just the presence of -- nature can improve a community's health, such as through a reduction in diabetes rates and stress-related conditions like heart disease. Moreover, other studies have shown that a lack of access to nature is tied to poorer outcomes, such as research that tied tree loss to increased cardiovascular and respiratory deaths.

South believes that this evidence demonstrates that health systems and health care providers should make more of an effort to increase greenspace access, or "prescribe doses" of it, to potentially boost community health as a result.

"Now, we need to specify how much of nature, or how accessible it needs to be, for people to get positive benefits - and negate any deficiencies," South wrote in the journal.

A way that health care can be adjusted to factor in nature is to have clinicians incorporate assessments of a person's access to it during patient encounters. This could be done by adding simple questions gauging a person's feelings toward nature, how much time they are able to spend in it, and where they are able to access it. Possible interventions could be as simple as a primary care physician looking up parks or trails nearby so that they're aware of what is accessible. Clinicians could also refer patients to community groups working on increasing green areas.

South pointed out that even if there is an embrace of "prescribing" nature, it can't be a one-size-fits-all approach, much the same as any other prescription. Factors such as a person's mobility or whether they have a condition like asthma may affect how they can interact with certain green spaces. Racial minorities may feel unwelcome in public green spaces, which must also be discussed.

And while she said any person involved in a health system can provide guidance for nature exposure, South suggested that community health workers, who already live and work in the areas where these interventions would take place, might be best suited. Their knowledge of and relationships with people in the area would inform the best practices for health systems to address deficiencies in access to nature.

Over the last two years, health systems have spent more than $2.5 billion addressing social determinants of health. As such, there is the capacity and the infrastructure in place for them to also address nature access, South explained. That could come in the form of something as simple as vacant lot greening, which has been demonstrated by South and colleagues to reduce violent crime, increase social cohesion, and reduce feelings of depression for nearby community members. Health systems could merge different initiatives to address social determinants of health, like investing in affordable housing that also has access to green space.

"There may be an economic argument to make for investing in greenspace," South said. "I am conducting a study now to see if vacant lot greening reduces emergency department visits for stress-related conditions. Tree canopy coverage is another example: Trees reduce urban heat islands, and high heat on summer days is associated with worse outcomes for people with chronic disease."

As of late, there has been renewed interest in the outdoors due to stay-at-home orders and social distancing. Reddit data shows that toward the beginning of the outbreak, many were questioning whether they could safely go outside. South's paper was written before the COVID-19 outbreak, but its points are especially timely.

South said she's seen people in cities are spending time outside like never before, and she hopes healthcare providers will "jump on this wave" to discuss its benefits with their patients. But just like other social determinants of health, South sees lack of access to nature correlating with differences in COVID-19 infections.

"Layered on top of a lack of access to greenspace, economic and educational inequities, the criminal justice system and housing, you have a system of structural racism that has worked to create the disparities we see in COVID today," South said.

Pesticides, pharmaceutical products, and endocrine disruptors are some of the emerging contaminants often found in treated domestic wastewater, even after secondary treatment. Professor Patrick Drogui of the Institut national de la recherche scientifique (INRS) and his team have tested the effectiveness of a tertiary treatment process using electricity in partnership with the European Membrane Institute in Montpellier (IEM) and Université Paris-Est.

The advanced electro-oxidation process (EOA) uses two electrodes to break down non-biodegradable pollutants that remain after biological treatment. Electric current is passed through the electrodes, generating hydroxide radicals (* OH), which attack the refractory molecules. The primary advantage of this method is that it does not require any chemicals to be added to the water.

"EOA processes are revolutionary in the field of wastewater treatment. It's pioneering technology for treating wastewater contaminated by refractory pollutants such as pharmaceutical wastes," said Professor Patrick Drogui, co-author of the study published on June 18 in the prestigious journal Science of the Total Environment.

The researchers tested new catalytic electrodes. "We have shown that these electrodes are effective and produce large quantities of hydroxide radicals. They are also cheaper than the other electrodes currently on the market, which reduces the cost of the treatment," said Yassine Ouarda, Ph.D. student and first author on the study.

Versatile Tertiary Treatment

Researchers tested the technology on three types of water coming from different treatment processes: conventional, membrane bioreactor, and a treatment process that separates wastewater, including feces, at the source. They focused on paracetamol, otherwise known as acetaminophen. "We tested the process on this particular molecule because it's one of the world's most widely used drugs. We have already tested it at INRS for some 15 different pollutants, as the process can be used for other pharmaceutical molecules," said Mr. Ouarda.

During partial breakdown of pollutants such as pharmaceuticals, the by-products can be more toxic than the parent compounds. "We observed that the toxicity of the solution increased and subsequently decreased during treatment. This indicates that the toxic molecules are themselves broken down if the reaction continues," said Mr. Ouarda.

"This work once again confirms that advanced electro-oxidation processes are good candidates for breaking down drug wastes left behind after biological treatment," said Professor Drogui.

BLOOMINGTON, Ind. -- COVID-19 has placed tremendous pressure on health care systems, not only for critical care but also from an anxious public looking for answers.

Research from the Indiana University Kelley School of Business found that chatbots -- software applications that conduct online chats via text or text-to-speech -- working for reputable organizations can ease the burden on medical providers and offer trusted guidance to those with symptoms.

Researchers conducted an online experiment with 371 participants who viewed a COVID-19 screening session between a hotline agent -- chatbot or human -- and a user with mild or severe symptoms.

They studied whether chatbots were seen as being persuasive, providing satisfying information that likely would be followed. Their results showed a slight negative bias against chatbots' ability, perhaps due to recent press reports. When the perceived ability is the same, however, participants reported that they viewed chatbots more positively than human agents, which is good news for health care organizations struggling to meet user demand for screening services.

"The primary factor driving user response to screening hotlines -- human or chatbot -- is perceptions of the agent's ability," said Alan Dennis, the John T. Chambers Chair of Internet Systems at Kelley and corresponding author of the paper, "User reactions to COVID-19 screening chatbots from reputable providers." "When ability is the same, users view chatbots no differently or more positively than human agents."

Other authors on the paper, forthcoming in the Journal of the American Medical Informatics Association, are Antino Kim, assistant professor of operations and decision technologies at Kelley; and Sezgin Ayabakan, assistant professor of management information systems, and doctoral candidate Mohammad Rahimi, both at Temple University's Fox School of Business.

Even before the pandemic, chatbots were identified as a technology that could speed up how people interact with researchers and find medical information online.

"Chatbots are scalable, so they can meet an unexpected surge in demand when there is a shortage of qualified human agents," Dennis, Kim and their co-authors wrote, adding that chatbots "can provide round-the-clock service at a low operational cost.

"This positive response may be because users feel more comfortable disclosing information to a chatbot, especially socially undesirable information, because a chatbot makes no judgment," researchers wrote. "The CDC, the World Health Organization, UNICEF and other health organizations caution that the COVID-19 outbreak has provoked social stigma and discriminatory behaviors against people of certain ethnic backgrounds, as well as those perceived to have been in contact with the virus. This is truly an unfortunate situation, and perhaps chatbots can assist those who are hesitant to seek help because of the stigma."

The primary factor driving perceptions of ability was the user's trust in the provider of the screening hotline.

"Proactively informing users of the chatbot's ability is important," the authors wrote. "Users need to understand that chatbots use the same up-to-date knowledge base and follow the same set of screening protocols as human agents. ... Because trust in the provider strongly influences perceptions of ability, building on the organization's reputation may also prove useful."

UNIVERSITY PARK, Pa.-- Over time goldenrod plants and the gall flies that feed on them have been one-upping each other in an ongoing competition for survival. Now, a team of researchers has discovered that by detecting the plants' chemical defenses, the insects may have taken the lead.

According to John Tooker, professor of entomology, this complex scenario begins when a female gall fly (Eurosta solidaginis) lays its eggs in the leaf bud of a goldenrod plant (Solidago altissima). This action forces the plant to produce a tumor-like growth, called a gall. This gall, he said, provides the fly larvae with a source of nutrition and safety from predators and the environment but decreases the plants' ability to reproduce.

"Our previous research showed that goldenrod plants have evolved to 'eavesdrop' on the sexual communications of their gall fly herbivores -- specifically, the sex pheromones used by males to attract females," he said. "Our new research, suggests that the plants respond to this 'intelligence' by strengthening, also known as 'priming,' chemical defenses to prevent females from laying eggs and inducing gall formation."

Eric Yip, postdoctoral scholar in the Department of Entomology, Penn State, explained that this plant-insect dynamic is similar to the reversals of fortune that occur in the "Spy vs. Spy" comic strip, only the characters are a plant and an insect rather than a pair of cartoon drawings.

To investigate the effects of priming, the researchers in their new study exposed almost 300 goldenrod plants comprising 11 genetic types -- or genotypes -- to male flies that varied in age, from one to four weeks old, as well as a control in which the plants were not exposed to flies. Next, the team allowed already-mated females to access the plants, and they counted the number of times a female inserted her ovipositor -- egg-laying device -- into the flower buds as a measure of her preference for particular plants. The team then tracked gall formation.

The findings appear today (July 9) in the Journal of Ecology.

The scientists found that although priming led to reduced gall formation overall, its effects varied by the age of the male flies used for priming. Priming by younger males resulted in significantly fewer galls, while priming by older males yielded more galls.

"The female flies in our study appeared to 'know' -- likely via some sort of code breaking that we have yet to understand -- that their offspring would be most successful on plants that had been primed to a lesser degree by the older males.

The effects of priming also differed by plant genotype.

"One genotype became completely resistant to galling after priming, but another became more vulnerable when exposed to older male flies," said Yip. "So, the plant evolved to protect itself against the fly, and subsequently the fly, at least on some plant genotypes, has evolved to make galls more likely."

The team plans to next investigate how flies, through their avoidance of primed plants, may be asserting further selective pressure on the evolution of this defense.

"Ultimately," Tooker said, "the findings could have practical applications in agriculture, perhaps enabling us to enhance crop plants' defenses against pests without the use of toxic pesticides."

WHAT

Falls are the leading cause of injury-related death among older Americans and lead to 3 million emergency department visits every year. About one out of every three adults age 65 or older falls each year. To assess the delivery and implementation of effective strategies for preventing these injuries, the Patient-Centered Outcomes Research Institute (PCORI) and National Institute of Aging of the National Institutes of Health supported the STRIDE Study. As reported online in the New England Journal of Medicine, the STRIDE Study found that a personalized approach to falls risk reduction, in which nurses tailored falls prevention plans for older adults at high risk and administered these plans for at least 20 months, resulted in about an 8% to 10% reduction in serious fall injuries, but this effect was not statistically significant. Potential barriers to care, such as transportation availability and copayments and lack of engagement in reducing some risk factors, such as eliminating medications that increase falls risk, are among possible reasons the paper notes for the lesser effect size seen in the trial.

STRIDE was a multisite, randomized pragmatic trial. It was conducted at 86 primary care sites nationwide and included rural, urban, and suburban sites. The trial enrolled community-dwelling older adults at risk for falling who reflected the general population of older adults across the nation. Nurses trained as Falls Care Managers helped participants in the intervention group to identify their risk factors and select which risk reduction strategies they were willing and able to implement. Control group participants received their usual care plus educational material on falls information and were encouraged to discuss fall prevention with their primary care doctors, who also received the participants' risk factor screening results.

Spokespeople from PCORI can provide important context about this study, including:

Why there is the need for research assessing the most effective ways to deliver and promote the use of prevention strategies that have been shown to be useful in previous research

The importance of pragmatic studies for providing evidence about how well healthcare approaches work in everyday situations and circumstances

Providing background on patient-centered research and the value of engagement of healthcare decision makers in the research process

WHEN AND WHO

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

Nakela L. Cook, MD, MPH, Executive Director

Steven Clauser, PhD, MPA Program Director, Science

ADDITIONAL BACKGROUND

STRIDE was 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 large trial enrolled more than 5,400 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 conducted after small-scale trials showed that interventions to reduce risk factors can reduce the rate of falls and fall injuries. STRIDE participants were asked to take steps to lessen one to three of seven risk factors using risk reduction strategies shown to be effective in prior research. In some cases, participants did not address important risk factors; therefore, it is possible that some participants' risk reduction may not have been optimal. The findings suggest that in typical clinical care settings, older adults may face difficulties that may affect their ability to select or follow optimal risk reduction interventions. Lessons learned from STRIDE can help inform the design and implementation of future clinical trials of fall injury risk reduction in various healthcare delivery settings.

What The Article Says: The response of a physician to the fear and despair associated with COVID-19 is described in this article.

Author: Siu-Hin Wan, M.D., of the Mayo Clinic in Rochester, Minnesota, is the author.

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

(doi:10.1001/jamacardio.2020.2420)

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

Months of self-isolation and social distancing have taken their toll. Sheldon Cohen, the Robert E. Doherty Professor of Psychology at Carnegie Mellon University, has produced a body of research that suggests that interpersonal stressors many are experiencing during quarantine are associated with an increased vulnerability to upper respiratory viruses and perhaps coronavirus. A summary of his work is available online in the July 8 issue of Perspectives on Psychological Science.

"We know little about why some of the people exposed to the coronavirus that causes COVID-19, are more likely to develop the disease than others. However, our research on psychological factors that predict susceptibility to other respiratory viruses may provide clues to help identify factors that matter for COVID-19," said Cohen.

Cohen has spent his career examining the impact of different behavioral, social and psychological factors on the development of upper respiratory illnesses. Through a series of viral challenge studies, he examined how such factors can affect whether or not healthy adults exposed to respiratory viruses become ill. His work has focused on eight viral strains that cause a common cold (rhinovirus types 2, 9, 14, 21, 39 and Hanks, as well as respiratory syncytial virus and corona virus 229E) and two that cause influenza (A/Kawasaki/86 H1N1; and A/Texas/36/91).

"The focus on the pandemic up until now has been changing behaviors to avoid exposure to the virus," said Cohen. "In our work, we intentionally exposed people to cold and influenza viruses and studied whether psychological and social factors predict how effective the immune system is in suppressing infection, or preventing or mitigating the severity of illness."

Cohen's work has pointed to the importance of social and psychological factors in the development of infection and illness. This work may hold clues to the health implications of the on-going quarantine.

To slow the spread of coronavirus, many communities issued stay-at-home measures, increasing interpersonal stressors, like loneliness, loss of employment and familial conflict. According to Cohen, these stressors may be powerful predictors of how a person will respond if exposed to coronavirus.

In a series of studies, he found participants experiencing interpersonal stressors had a greater chance of developing an upper respiratory illnesses when exposed to cold viruses. Cohen believes interpersonal stressors might play a similar role in response to the coronavirus causing COVID-19, increasing a person's vulnerability to infection and illness.

In addition, both social and psychological stressors increased the production of cytokines, molecules that promote inflammation in response to infection. In Cohen's work, psychological and social stressors were associated with an overproduction of pro-inflammatory cytokines in response to cold and influenza viruses. In turn, this excess of inflammation was associated with an increased risk of becoming ill. Similarly, research on COVID-19 has shown that producing an excess of pro-inflammatory cytokines is associated with more severe COVID-19 infections suggesting the hypothesis that a stress-triggered excessive cytokine response might similarly contribute to excessive inflammation and symptoms in COVID-19.

While social and psychological stressors increase susceptibility, Cohen's work also indicates that social integration and social support offer a protective shield against respiratory infection and illness.

"If you have a diverse social network (social integration), you tend to take better care of yourself (no smoking, moderate drinking, more sleep and exercise)," said Cohen. "Also if people perceive that those in their social network will help them during a period of stress or adversity (social support) then it attenuates the effect of the stressor and is less impactful on their health."