Culture

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."

The genome in mitochondria -- the cell's energy-producing organelles -- is involved in disease and key biological functions, and the ability to precisely alter this DNA would allow scientists to learn more about the effects of these genes and mutations. But the precision editing technologies that have revolutionized DNA editing in the cell nucleus have been unable to reach the mitochondrial genome.
 

Now, a team at the Broad Institute of MIT and Harvard and the University of Washington School of Medicine has broken this barrier with a new type of molecular editor that can make precise C* G-to-T* A nucleotide changes in mitochondrial DNA. The editor, engineered from a bacterial toxin, enables modeling of disease-associated mitochondrial DNA mutations, opening the door to a better understanding of genetic changes associated with cancer, aging, and more.
 

The work is described in Nature, with co-first authors Beverly Mok, a graduate student from the Broad Institute and Harvard University, and Marcos de Moraes, a postdoctoral fellow at the University of Washington (UW).
 

The work was jointly supervised by Joseph Mougous, UW professor of microbiology and an investigator at the Howard Hughes Medical Institute (HHMI), and David Liu, the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad Institute, professor of chemistry and chemical biology at Harvard University, and HHMI investigator.
 

"The team has developed a new way of manipulating DNA and used it to precisely edit the human mitochondrial genome for the first time, to our knowledge -- providing a solution to a long-standing challenge in molecular biology," said Liu. "The work is a testament to collaboration in basic and applied research, and may have further applications beyond mitochondrial biology."
 

Agent of bacterial warfare
 

Most current approaches to studying specific variations in mitochondrial DNA involve using patient-derived cells, or a small number of animal models, in which mutations have occurred by chance. "But these methods pose major limitations, and creating new, defined models has been impossible," said co-author Vamsi Mootha, institute member and co-director of the Metabolism Program at Broad. Mootha is also an HHMI investigator and professor of medicine at Massachusetts General Hospital.
 

While CRISPR-based technologies can rapidly and precisely edit DNA in the cell nucleus, greatly facilitating model creation for many diseases, these tools haven't been able to edit mitochondrial DNA because they rely on a guide RNA to target a location in the genome. The mitochondrial membrane allows proteins to enter the organelle, but is not known to have accessible pathways for transporting RNA.
 

One piece of a potential solution arose when the Mougous lab identified a toxic protein made by the pathogen Burkholderia cenocepacia. This protein can kill other bacteria by directly changing cytosine (C) to uracil (U) in double-stranded DNA.
 

"What is special about this protein, and what suggested to us that it might have unique editing applications, is its ability to target double-stranded DNA. All previously described deaminases that target DNA work only on the single-stranded form, which limits how they can be used as genome editors," said Mougous. His team determined the structure and biochemical characteristics of the toxin, called DddA.
 

"We realized that the properties of this 'bacterial warfare agent' could allow it to be paired with a non-CRISPR-based DNA-targeting system, raising the possibility of making base editors that do not rely on CRISPR or on guide RNAs," explained Liu. "It could enable us to finally perform precision genome editing in one of the last corners of biology that has remained untouchable by such technology -- mitochondrial DNA."
 

"Taming the beast"
 

The team's first major challenge was to eliminate the toxicity of the bacterial agent -- what Liu described to Mougous as "taming the beast" -- so that it could edit DNA without damaging the cell. The researchers divided the protein into two inactive halves that could edit DNA only when they combined.
 

The researchers tethered the two halves of the tamed bacterial toxin to TALE DNA-binding proteins, which can locate and bind a target DNA sequence in both the nucleus and mitochondria without the use of a guide RNA. When these pieces bind DNA next to each other, the complex reassembles into its active form, and converts C to U at that location -- ultimately resulting in a C* G-to-T* A base edit. The researchers called their tool a DddA-derived cytosine base editor (DdCBE).
 

The team tested DdCBE on five genes in the mitochondrial genome in human cells and found that DdCBE installed precise base edits in up to 50 percent of the mitochondrial DNA. They focused on the gene ND4, which encodes a subunit of the mitochondrial enzyme complex I, for further characterization. Mootha's lab analyzed the mitochondrial physiology and chemistry of the edited cells and showed that the changes affected mitochondria as intended.
 

"This is the first time in my career that we've been able to engineer a precise edit in mitochondrial DNA," said Mootha. "It's a quantum leap forward -- if we can make targeted mutations, we can develop models to study disease-associated variants, determine what role they actually play in disease, and screen the effects of drugs on the pathways involved."
 

Future developments
 

One goal for the field now will be to develop editors that can precisely make other types of genetic changes in mitochondrial DNA.
 

"A mitochondrial genome editor has the long-term potential to be developed into a therapeutic to treat mitochondrial-derived diseases, and it has more immediate value as a tool that scientists can use to better model mitochondrial diseases and explore fundamental questions pertaining to mitochondrial biology and genetics," Mougous said.
 

The team added that some features of DdCBE, such as its lack of RNA, may also be attractive for other gene-editing applications beyond the mitochondria.
 

A rat is less likely to help a trapped companion if it is with other rats that aren't helping, according to new research from the University of Chicago that showed the social psychological theory of the "bystander effect" in humans is present in these long-tailed rodents.

The study, titled "The Bystander Effect in Rats," also demonstrated that in the presence of other potential helper rats, rats are more, rather than less, likely to help. Whether helping is facilitated or suppressed depends on the circumstances rather than on personal temperament or morals, a finding with implications for human society. The research, published in the July 8 issue of Science Advances, builds off previous research on rat empathy.

In 2011, Peggy Mason, PhD, professor of neurobiology and senior author of the study, and her UChicago team of researchers found that rats consistently freed trapped companions, even saving a bit of chocolate for them, and this behavior was driven by a rat version of empathy. A subsequent study showed that rats treated with anti-anxiety medication are less likely to free a trapped peer because they do not feel its anxiety. In another study, researchers found that rats only freed trapped rat strains that they had previous social experience with.

The roots of the classic bystander effect date back to 1964, when Catherine "Kitty" Genovese was murdered in a crowded residential neighborhood in Queens, New York. An account published in the New York Times reported that 38 bystanders saw the murder but did not intervene. Though this story was later proven inaccurate, it inspired psychologists Bibb Latané and John Darley to investigate why so many people would fail to help.

The pair tested human subjects alone and in the presence of "confederate" bystanders -- people who were part of the research team and were instructed not to help -- as they confronted a variety of experimental scenarios with someone (an actor) in distress. Latané and Darley consistently observed that subjects were far less likely to help in the presence of non-helping confederates than they were when tested alone. This phenomenon, referred to as the bystander effect, is now a pillar in psychology, included in every introductory textbook and class. The mechanism for the classic bystander effect is thought to be a diffusion of responsibility whereby people reason that they need not act because others in a group will.

First author John Havlik was a UChicago undergraduate in Mason's laboratory, when the topic of the bystander effect came up during a lab meeting.

"My students had been bugging me to do this experiment for years," said Mason. "But it wasn't until John came along and would not let the idea go that we took the plunge."

Havlik, now a student at the Yale School of Medicine, spearheaded experiments to examine whether rats, which lack complex reasoning skills, would show a classical bystander effect.

The research team used their trapped rat paradigm in combination with rats that were made into "confederates" by administering an antianxiety drug that made them indifferent to another rat's distress, ensuring that they would not help. The team found that rats tested with confederates were less likely to help than those tested alone -- a bystander effect in rats. Digging deeper, they saw that the presence of confederates blocked reinforcement for helping.

"It's worse to have a non-responsive audience than to be alone," Mason said. "The rats try helping, but it's just not a rewarding experience because the other rats don't appear to care. It's as though the rat was saying to himself, 'I helped yesterday and no one cared. Not doing that again.' "

Mason and her team then wanted to know how the presence of untreated rats affected the helping behavior. Counter to the prediction of the bystander effect, duos and trios of rats actually were more likely to help than solo rats.

"At first, I thought the experiment had failed," Havlik said. "But after doing more research into human studies, we realized that behavior has actually been mirrored in people, too."

In research published last year, an analysis of surveillance videos revealed that groups of bystanders helped in more than 90% of violent encounters.

"The reason we see these patterns of helpfulness goes deeper than the lessons we learned in kindergarten about being nice to each other," said study co-author Maura Jacobi, MD, a 2020 graduate of the University of Chicago Pritzker School of Medicine and co-first author of the study. "This is a phenomenon that's not exclusive to humans."

CAMBRIDGE, MA - Microparticles offer a promising way to deliver multiple doses of a drug or vaccine at once, because they can be designed to release their payload at specific intervals. However, the particles, which are about the size of a grain of sand, can be difficult to inject because they can get clogged in a typical syringe.

MIT researchers have now developed a computational model that can help them improve the injectability of such microparticles and prevent clogging. The model analyzes a variety of factors, including the size and shape of the particles, to determine an optimal design for injectability.

Using this model, the researchers were able to achieve a sixfold increase in the percentage of microparticles they could successfully inject. They now hope to use the model to develop and test microparticles that could be used to deliver cancer immunotherapy drugs, among other potential applications.

"This is a framework that can help us with some of the technologies that we've developed in the lab and that we're trying to get into the clinic," says Ana Jaklenec, a research scientist at MIT's Koch Institute for Integrative Cancer Research.

Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior authors of the study, which appears today in Science Advances. The paper's lead author is MIT graduate student Morteza Sarmadi.

Microparticle model

Microparticles range in size from 1 to 1,000 microns (millionths of a meter). Many researchers are working on using microparticles made of polymers and other materials to deliver drugs, and about a dozen such drug formulations have been approved by the FDA. However, others have failed because of the difficulty of injecting them.

"The major issue is clogging, somewhere in the system, that doesn't allow for the full dose to be delivered," Jaklenec says. "Many of these drugs don't make it past development because of the challenges with injectability."

Such drugs are usually injected intravenously or under the skin. Making sure that these drugs successfully reach their destinations is a key step in the drug development process, but it's one that is often done last, and can thwart an otherwise promising treatment, Sarmadi says.

"Injectability is a major factor in how successful a drug will be, but little attention has been paid to trying to improve administration techniques," he says. "We hope that our work can improve the clinical translation of novel and advanced controlled-release drug formulations."

Langer and Jaklenec have been working on developing hollow microparticles that can be filled with multiple doses of a drug or vaccine. These particles can be designed to release their payloads at different times, which could eliminate the need for multiple injections.

To improve the injectability of these and other microparticles, the researchers experimentally analyzed the effects of altering the size and shape of the microparticles, the viscosity of solution in which they are suspended, and the size and shape of the syringe and needle used to deliver them. They tested cubes, spheres, and cylindrical particles of different sizes, and measured the injectability of each one.

The researchers then used this data to train a type of computational model known as a neural network to predict how each of these parameters affect injectability. The most important factors turned out to be particle size, particle concentration in the solution, viscosity of the solution, and needle size. Researchers working on drug-delivering microparticles can simply input these parameters into the model and get a prediction of how injectable their particles will be, saving the time they would have had to spend building different versions of the particles and testing them experimentally.

"Instead of going through the experiments, and going back and forth, having no idea of how successful the system will be, you can use this neural network and it can guide you, early on, to have an understanding of the system," Sarmadi says.

Injectability boost

The researchers also used their model to explore how changing the shape of the syringe could affect injectability. They came up with an optimal shape that resembles a nozzle, with a wide diameter that tapers toward the tip. Using this syringe design, the researchers tested the injectability of the microparticles they described in a 2017 Science study, and found that they boosted the percentage of particles delivered from 15 percent to almost 90 percent.

"This is another way to maximize the forces that are acting on the particles and pushing the particles toward the needle," Sarmadi says. "It's a promising result that shows that there's huge room for improvement in the injectability of microparticle systems."

The researchers are now working on designing optimized systems for delivering cancer immunotherapy drugs, which can help stimulate an immune response that destroys tumor cells. They believe these types of microparticles could also be used to deliver a variety of vaccines or drugs, including small-molecule drugs and biologics, which include large molecules such as proteins.

Chinese researchers recently discovered a protein quality control mechanism called "reubiquitination". The mechanism, according to the researchers, could promote the elimination of misfolded membrane proteins, minimize their dwell time in cells, and thereby reduce their probability to form toxic aggregates in human body.

Discovered by a research team from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences, the "reubiquitinase" RNF126 adds a small protein called ubiquitin to the unfolded membrane protein intermediates in the cytosol, and targets them to the degradation machinery, proteasome, for destruction.

Misfolded proteins in cells and organisms should be cleared by a protein quality control mechanism called ubiquitin-proteasome system. If not, they tend to form pathological aggregates that are believed to damage cells (e.g., neurons), and ultimately cause various diseases of aging, such as neurodegeneration.

The results show that RNF126-mediated reubiquitination is important for normal cell physiology. Without reubiquitination, targeting of misfolded proteins to the proteasome could be delayed, and this increase the risk of protein aggregation and cellular stress, which could gradually lead to various diseases.

In addition, the function of RNF126 as a reubiquitinase might be required for rapid proliferation of certain cancer cells, making it a potential therapeutic target.

This work has been published online in July 8, 2020 in Molecular Cell, and it was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, and the Shanghai Municipal Science and Technology Major Project.