Culture

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at https://www.acpjournals.org/topic/category/coronavirus.

Rapid, Living Practice Points from ACP: Update on remdesivir use for hospitalized COVID-19 patients

In updated Rapid, Living Practice Points (https://www.acpjournals.org/doi/10.7326/M20-8101), the American College of Physicians (ACP) addresses emerging evidence regarding the effectiveness of remdesivir in hospitalized patients with COVID-19 and whether benefits and harms vary by symptom duration, disease severity, and treatment duration. The paper, developed by the Scientific Medical Policy Committee of the ACP, Should Remdesivir Be Used for the Treatment of Patients with COVID-19? Rapid, Living Practice Points from the American College of Physicians (Version 2), was published today in Annals of Internal Medicine.

The ACP's updated Practice Points aim to target patients who will most benefit from the use of remdesivir and now suggests the following:

Consider remdesivir for 5 days to treat hospitalized patients with COVID-19 who do not require mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

Consider extending the use of remdesivir to 10 days to treat hospitalized patients with COVID-19 who require mechanical ventilation or ECMO within a 5-day course.

Avoid initiating remdesivir to treat hospitalized patients with COVID-19 who are already on mechanical ventilation or ECMO.

Based on a systematic review conducted by the Minneapolis VA Evidence Synthesis Program that has been updated through Dec. 7, 2020, this version represents a change from the previous classifications of "moderate" and "severe" disease to now describe disease severity according to respiratory support requirements [e.g. no requirement, supplemental oxygen, mechanical ventilation/ECMO].

Remdesivir is a broad-spectrum antiviral agent administered intravenously. It was authorized on Oct. 22, 2020, for emergency use for the treatment of COVID-19 in the U.S. by the Food and Drug Administration and in other countries.

ACP's Practice Points are developed by ACP's Scientific Medical Policy Committee and provide advice to improve the health of individuals and populations and promote high value care based on the best available evidence derived from assessment of scientific work (e.g. clinical guidelines, systematic reviews, individual studies). ACP Practice Points aim to address the value of screening and diagnostic tests and therapeutic interventions for various diseases, and consider known determinants of health, including but not limited to genetic variability, environment, and lifestyle.

The ACP Practice Points will be maintained as a "living" document and ACP's Scientific Medical Policy Committee will monitor emerging evidence to determine its impact on the main findings and conclusions, and issue updates as needed.

Media Contacts: The full text of the article is free to the public. Click on the link above to access the text. To speak with someone from ACP, please contact Andrew Hachadorian at AHachadorian@acponline.org
or (215) 351-2514.

Headlines like "Black Friday Shoppers Trampled in New York" and popular television shows such as "Extreme Couponing" remind us how crazy consumers can get about retail sales promotions. This enthusiasm for getting bargains has been termed "deal proneness."

Past research has indicated that, to some degree, people become deal prone through being taught by their parents. But a new paper, "Born to Shop? A Genetic Component of Deal Proneness," published in the Journal of the Association for Consumer Research, provides evidence that our genes also play a role in causing bargain-hunting enthusiasm.

To demonstrate this genetic factor, authors Robert Schindler, Vishal Lala, and Jeanette Taylor compared the deal-proneness similarity among 78 pairs of identical (monozygotic) twins with that among 43 pairs of fraternal (dizygotic) twins reared together. They measured interest in various types of deals, like promotions that involve discounts (e.g., "Receiving cash rebates makes me feel good") and promotions that involve bonuses (e.g., "I enjoy buying products that come with a free gift"). The results indicated that 70 percent of the variability in deal proneness is associated with variability in genetic factors.

"The greater deal-proneness similarity among identical twins than among fraternal twins provides strong evidence for the existence of a heritable component to deal proneness," the authors write. However, the fraternal twins who lived together did show more similarity in deal proneness than those who did not live together, which the authors note is evidence that it's not all heredity - shared experience also is a source of deal proneness.

Knowing that interest in bargains runs in families might suggest to retailers the value of using parent-child, grandparent, or other family settings in communicating about deals. However, this research also raises the question of how such a modern, culturally-dependent phenomenon such as deal proneness could be, even partially, in our genes. Future research that will help answer this question may also guide us to a deeper understanding of the sources of consumers' often striking enthusiasm for retail bargains.

A new study in Frontiers in Communication has demonstrated the powerful impact that subtle messaging and cues, or 'nudges', can provide on encouraging people to show socially desirable behaviors. Travelers who were observed on the Indonesian island of Gili Trawangan, a popular tourist destination, were more likely to demonstrate environmentally conscious actions, such as refusing a plastic bag or avoiding contact with a coral reef, when they were 'nudged' towards the desirable action with either a written or face to face interaction. The researchers found that any intervention, whether framed positively or negatively, was enough to lead people to make environmentally conscious decisions, compared to being given no behavioral cues or messaging. The study provides many practical takeaways that can be easily implemented by tourist operators or businesses, at a low cost, to increase environmental stewardship and promote positive behaviors in their customers.

Although many of us feel a responsibility to demonstrate environmentally-conscious behaviors and possess the knowledge we need to take these actions, we are often burdened by numerous obstacles, a phenomenon the researchers describe as the 'knowledge-action gap'. Dr Katherine Nelson, who led the study in partnership with the Gili Eco Trust, explains:

"The gap between knowledge and action exists because it is much easier to think a certain way than it is to actually consistently behave in that manner -- but providing a subtle cue can help us relieve some of the cognitive burden on our brains when we are in a complex environment."

To try and close this gap, the researchers set up scenarios for tourists in two real life situations -- when being offered a plastic bag at a convenience store, and when given a briefing before a snorkeling trip. The researchers observed the differences in people's behavior based on whether a person was confronted with a written or face to face interaction of either a positive message highlighting good outcomes, or a negative message focusing on the bad outcomes of a specific action.

The study showed that the presence of a 'nudge' or cue towards certain behaviors was enough to encourage people to behave in more environmentally conscious ways, whether that was refusing a plastic bag whilst at the convenience store or ensuring they maintained a safe distance from turtles when on a snorkeling trip - whether this message was framed positively or negatively did not matter.

"Our study highlights that an intervention can lead people to making better decisions by just drawing their attention to an issue -- by providing a small cue, we can reduce the obstacles that get in the way and make environmental behaviors easy."

The results offer important insights on the effectiveness of simple messaging as a practical way to nudge people towards environmentally conscious behaviors. The tourist sector in particular has huge potential to utilize these types of approaches and make pro-environmental behaviors a simple choice to reduce local impacts.

KEY STUDY FINDINGS INCLUDE:

2.9% of U.S. adults report a current peanut allergy.

About one in six adults with a peanut allergy developed it after age 18.

Approximately one in five adults with peanut allergy report visiting the emergency department for food allergy treatment each year.

Patients who developed their peanut allergy during adulthood are less likely to report having an epinephrine auto-injector prescription than those who developed their peanut allergy during childhood, despite similar frequencies of severe reactions among both groups.

CHICAGO --- Peanut allergy affects at least 4.5 million adults in the U.S., many of whom report developing their first allergy symptoms during adulthood, reports a new Northwestern Medicine study.

However, despite the fact that roughly three out of four Americans with peanut allergy are over 17 years old, peanut allergy is often considered a predominantly pediatric concern. For example, earlier this year the U.S. Food and Drug Administration (FDA) approved a peanut allergy therapy for initiation in pediatric patients ages 4-17. There are currently no FDA-approved therapies for patients with adult-onset food allergy.

The new study provides the first detailed estimates of peanut allergy among U.S. adults in all 50 states, which was previously unknown. These data indicate peanut allergy may be more common than previously acknowledged, and while younger adults are most affected, peanut allergy impacts U.S. adults of all ages.

"Currently, the sole FDA-approved peanut allergy therapy--Palforzia-- is only indicated for pediatric patients. Given the high prevalence of peanut allergy among U.S. adults, additional therapies are needed to help address this growing burden of disease," said senior study author Dr. Ruchi Gupta, professor of pediatrics at Northwestern University Feinberg School of Medicine and a physician at Ann & Robert H. Lurie Children's Hospital of Chicago.

Gupta also is director of the Center for Food Allergy and Asthma Research at Feinberg.

The paper will be published Feb. 9 in the Journal of Allergy and Clinical Immunology.

The study found 2.9% of U.S. adults report a current peanut allergy, while 1.8% report a physician-diagnosed peanut allergy and/or a history of peanut-allergic reaction symptoms. In addition, researchers found two in three adults with peanut allergy have at least one other food allergy--most commonly tree nuts but more than one in five are also allergic to shellfish.

The data also indicate many individuals who report peanut allergies and experience potentially severe allergic reactions are not obtaining clinical diagnosis of their allergies.

"Clinical confirmation of suspected food allergies, no matter when their reported onset, is critical to reduce the risk of unnecessary allergen exposure as well as to ensure patients receive essential counseling and prescription of emergency epinephrine," said study co-first author Dr. Dawn Lei, a clinical instructor of pediatrics at Feinberg and an allergist and immunologist at Edward Hines Jr. VA Hospital.

Christopher Warren, director of population health at Feinberg's Center for Food Allergy and Asthma Research and co-first author added, "Unlike allergies such as milk or egg, which often develop early in life and are outgrown by adolescence, peanut allergy appears to affect children and adults to a similar degree. Our study shows many adults are not outgrowing their childhood peanut allergies, and many adults are developing peanut allergies for the first time.

"Worryingly, despite reporting similar rates of severe reactions and annual food allergy-related emergency room visits, patients with adult-onset peanut allergy were less likely to report a physician-diagnosis as well as a current epinephrine prescription."

Together, these data suggest additional efforts are needed to ensure optimal food allergy diagnosis and management among adults with peanut allergy, study authors said.

Researchers at Baylor College of Medicine and other institutions have identified a novel strategy that can eliminate bacteria in a specific location before they cause an infection. The strategy uses a phage, a virus that infects and destroys bacteria, that can specifically locate in the same place the bacteria live in the gastrointestinal tract. The proximity between phage and bacteria facilitates the phage's attack and subsequent elimination of the bacteria.

This strategy has the potential of becoming a game changer in the fight against antibiotic-resistant bacteria that live in hard-to-reach places, such as the mucus layer of the gut. The study appears in the journal mBIO.

"Phages are very specific in their ability to infect and destroy certain species or strains of bacteria and not others, such as good bacteria. In the U.S., phage therapy is increasingly becoming an available option to treat antibiotic-resistant bacterial infections, a serious health concern," said first author Dr. Sabrina Green, director of research and development for TAILΦR labs at Baylor.

Antibiotic-resistant bacteria, such as ExPEC ST131, can colonize the human intestine without causing disease, but they also can exit the gut and infect other organs. For instance, these bacteria have been associated with infections of the urinary tract, brain, peritoneum, peripheral organs, blood and in-dwelling devices, such as urinary catheters, vascular devices, feeding tubes and wound drains, resulting in 9 million infections per year.

The team showed in previous work that phages can effectively treat an infection caused by ExPEC ST131 bacteria. In this study, they wanted to see if they could use phages to remove these bacteria to prevent an infection.

Finding the right phage

Many phages have a hard time fighting bacteria in the gut. The team discovered that there is a factor present in mammalian intestines that prevents phages from destroying bacteria. They identified the factor as mucin, sticky proteins that form a layer between intestinal epithelial cells and the layer of microorganisms.

The researchers reasoned that although mucins prevent many phages from infecting bacteria, there may be some that have evolved a way to counter the effect of mucins and, as a result, are able to target bacteria in high-mucin environments.

"We screened human sewage and animal feces for phages with unique properties that facilitate their ability to destroy bacteria in the presence of mucins," said corresponding author Dr. Anthony Maresso, associate professor of molecular virology and microbiology at Baylor. "We discovered a novel phage called ES17 that binds to mucins, and this property seemed to enhance its ability to infect bacteria in mucin-rich environments, such as the gut."

Further studies looked closer at this novel phage-mucin interaction. Green, Maresso and their colleagues discovered that phage ES17 binds to particular molecules called heparan sulfate which can be found not only in mucins, but also on the surface of various cells types, including epithelial cells. This prompted the researchers to investigate whether binding to heparan sulfate on epithelial cells, which the researchers had also discovered is the same binding site used by ES17's host bacteria ExPEC, would contribute to ES17's ability to target and destroy the bacteria in the gut environment.

"We tested the effect of phage ES17 on its bacterial host ExPEC in a murine intestine, comparing it with phages known to be unable to infect their bacterial host in complex environments," Green said. "We found that only ES17 had the unique ability to target and eliminate ExPEC bacteria in animal models."

A novel strategy to prevent bacterial infections

Taken altogether, the findings suggest that the ability of phage ES17 to bind to heparan sulfate on mucin-rich surfaces and directly on mammalian epithelial cells mediates its localization in areas deep in the gut where reservoirs of bacteria may be present. The researchers propose that being close to ExPEC bacteria facilitates phage invasion and bacterial elimination before they have the opportunity to exit the gut and infect other organs.

"Phages are viruses that specialize in invading and eliminating specific bacteria. Here we have shown the first phage that also binds to epithelial human cells and that this property mediates a novel mechanism for fighting bacterial infections we call positional targeting, as it enables the phage to anticipate where the bacteria it targets will be located," Maresso said. "We foresee the possibility that positional targeting will be the way smart drugs work in the future. Drugs won't be just distributed all through the body in the hopes that some of it will end in the right spot. The drugs of the future will go only precisely where they are supposed to work. Our work with phages is the first case in which this has been achieved."

The world is changing rapidly and in order to serve the human population dealing with those changes, American universities need to change, too. In fact, their role is to model the resiliency that all institutions need to embrace, according to Arizona State University President Michael M. Crow.

While many leading universities are poised to advance society and help respond to the challenges of disruptive change through their traditional role in education and discovery, many face a number of barriers that make them less prepared to respond to the rapidly changing conditions and the demands they create.

What is emerging is a new type of university, one that steps beyond the American research university model and is nimble and responsive, takes responsibility for what happens outside its walls and can scale up to meet the demands and challenges of modern society. ASU President Michael Crow says they are part of the "fifth wave" of universities.

Crow's comments came today (Feb. 9, 2021) at the annual meeting of the American Association for the Advancement of Science. Crow's presentation, "A new evolution of research universities," touched on the history of universities, outlined the challenges they face today and explained how new universities of the fifth wave will rise to meet those challenges.

In his recent book "The Fifth Wave," (written with ASU senior research fellow William Dabars) Crow describes the emerging standard of research universities that will better align them with the needs of society in many ways, including contributing solutions to global problems.

The fifth wave is a manifestation of a new wave of American universities, a model embraced and advanced by Arizona State University. These universities are egalitarian, accessible, based in community impact and measured against social outcomes. They are scalable, they are technologically sophisticated and advanced. They educate not hundreds of students, but thousands and tens of thousands of students, Crow said.

Many of today's leading universities are American research universities, which emerged nearly 140 years ago - the fourth wave of university evolution. These universities have a long history of contributions to society, such as breakthrough advances in the fundamental understanding of nature, advancing applied science on a multitude of fronts, and advancing human culture, human's sense of place and sense of self.

"This has all has been fantastic, but inadequate," Crow said. "Because what happened during the evolution of the research university is that it has become more exclusive, more limited to smaller and smaller fragments of society, and more and more isolated from larger aspects of society itself."

The COVID-19 pandemic is a case in point on the limits of the traditional research university.

"America's universities were about as unprepared for this pandemic as one could possibly imagine," Crow said. "Suddenly, we didn't know how to communicate science well enough, we didn't know how to engage in complexity well enough, we didn't know how to cut and cross between disciplines well enough, and we didn't know how to build confidence around knowledge well enough."

The pandemic shows that what is needed is an additional type of university, not a replacement for the ones that exist and are exemplars today, but an additional type of higher educational institutions. "The fifth wave will allow us to do it," Crow said.

The "new" universities are responsive to the rapidly evolving needs of society. Their hallmarks include being inclusive in their educational philosophy and understanding that all people are lifelong learners; contributing to the challenges humans face today on a grand scale, like climate change and the current pandemic; taking stock in their immediate surroundings and being responsible for the success of that setting and of society as a whole.

"We are faced with an evolutionary moment. The role of the university, its role in discovery, its role in creativity, its role in innovation has never been more important and also its limits have never been clearer," Crow said. "The significant role going forward is figuring out the role of existing research universities and the role of emerging universities, including those that need to operate at a new scale, a new speed and a new egalitarianism."

Crow warned, though, that certain barriers exist that can thwart the evolution of fifth wave universities.

"We form athletic leagues, but we don't form climate change research leagues," he said. "The current model is to have faculty largely work in small centers and small groups, each attempting to advance their fields in a highly competitive way to beat out their competitors. This leaves little room for working on the scaled problems, like how do we manage our relationship with the planet, how will we facilitate cultural and economic competitiveness and do so to the benefit of a highly diverse population. How do we map between Western science, Western culture, Western technology and Indigenous science, Indigenous culture and Indigenous technology?"

Crow explained that in shaping the New American University model is the idea that the university will take responsibility for actions outside of the institution itself.

"If K-12 is underperforming, the institution is partly responsible," Crow said. "If 50% of students graduating from high school are inadequately prepared for the society in which we live, the universities and colleges are partly responsible."

Once the institution takes on that responsibility outside of its walls, then its contribution to society becomes real in a daily way.

"Then we will have the emergence of a new type of American research university, one which is devoted to the actual measured success of the society in which it is embedded," Crow added. "Not in an abstract intergenerational way but in a functional way. In a day-to-day way."

Today, the average American is unlikely to spend time worrying about malaria. Although the disease is commonly perceived to be restricted to other parts of the world, it played a significant role in shaping American history. It even helped turn the tide of the American Revolutionary War by infecting so many British soldiers that General Cornwallis was forced to surrender at Yorktown.

First-year students in a 2019 introductory seminar class led by Erin Mordecai, an assistant professor of biology in the School of Humanities and Sciences (H&S), delved into this and other historical examples of how vector-borne diseases - those caused by infectious pathogens spread by living organisms or "vectors" - influenced human history. Throughout the course, they collaborated on a paper highlighting various trends in which these illnesses impacted historical societies. Their findings have now been published in the latest issue of the journal Ecology Letters.

"The mechanisms and consequences of vector-borne diseases are multimodal and far more pervasive than we had previously thought," said Tejas Athni, a student in the seminar and first author of the paper.

As Athni and his fellow students conducted their research, they discovered recurring themes across societies throughout time. One theme was that diseases don't affect all populations equally - a simple fact that had major ramifications throughout history. In the case of the American Revolution, many Americans had grown up in the South and were exposed to malaria young, allowing them to develop immunity. This granted them a strategic advantage over the less immune British army, which ended up being decimated by the disease.

A more sobering trend unearthed by the group's investigations was that disease tended to prey on inequities in societies, leaving marginalized groups most at risk. Both intentionally and unintentionally, it was weaponized time and again to enforce unjust hierarchies of power. In the American South, for instance, enslaved Black people were often forced to work in conditions that left them exposed to mosquitoes and made them much more vulnerable to malaria. To make matters worse, this inequity was used by white people to encourage the racist belief at the time that Black Americans were morally inferior and to justify Jim Crow segregation laws in the South.

Racism and disease

When Mordecai first submitted her class's paper for journal publication, it was rejected, with one reviewer citing the paper's failure to explore the relationship between racism and disease. Taking a more interdisciplinary approach, Mordecai then invited the reviewer, Nita Bharti, the Huck Early Career Professor of Biology at Penn State University, and Steven O. Roberts, an assistant professor of psychology in H&S and a race scholar, to speak to her class about systems of inequality from psychological and historical standpoints.

"We were taken aback by the extent to which the impacts of vector-borne disease have historically splintered across racial and societal lines," said Athni.

Structural racism, including what neighborhoods people can live in and their access to intergenerational wealth, is linked to disparities in rates of diabetes, hypertension and other chronic diseases associated with stress, Mordecai explained. These disparities are also apparent in the COVID-19 pandemic, where the disease's outcomes are more serious for individuals suffering with these conditions. This disproportionate burden further amplifies the vulnerability of already disadvantaged communities.

"When you layer on an emerging pandemic with existing health disparities, it disproportionally affects Black and Hispanic communities," said Mordecai.

Racial disparities also put historically marginalized communities at greater risk of being exposed to the virus. These communities, for instance, are more likely to be essential workers, lacking the luxury to safely shelter in place or have their groceries delivered.

"It's easy to think that communities of color aren't social distancing enough or not practicing proper hygiene," said Roberts, who is a co-author on the paper. "But that thinking completely neglects the social conditions that have made those communities more vulnerable to begin with."

The relationship between COVID-19 and structural inequality is unfortunately not limited to just modern times or the U.S. This too is a pattern that has repeated throughout history and across the globe. Outbreaks of leishmaniasis, a vector-borne disease spread by phlebotomine sand flies, have impacted hundreds of thousands of Syrians within refugee camps, a result of overcrowding in areas with poor sanitation. And when the first few cases of the Ebola outbreak popped up in 2014 in Africa, scientists in the United States were slow in finding ways to combat it until it showed up closer to home.

The authors hope that this paper will motivate scientists to be more proactive in protecting people in historically disadvantaged communities from disease.

"The paper does a spectacular job documenting the problem," said Roberts. "Now it will be important to maintain an interdisciplinary focus that can dismantle it."

Centering equity

Mordecai believes the paper produced as a result of her class is unique in the ecological literature. As the work underwent the peer review process, editors originally commented that it didn't feel like an ecological study at all. However, since the Black Lives Matter protests in the spring of last year, she said she is seeing a growing number of epidemiologists recognizing the role of racism in infectious disease transmission.

Athni, now a junior working on his honors thesis on statistically modeling the effects of climate on global mosquito distributions, said that being involved in this project has influenced the way he conducts research as a growing biologist.

"Dr. Mordecai's freshman seminar shaped my entire Stanford journey through an interdisciplinary lens," Athni said. "Moving forward, it's imperative that research explicitly recognizes and combats the structural racism, classism and sexism that continue to perpetuate environmental and health inequities. Equity must be brought to the center of ecology and global health in order to make meaningful progress for all of humanity."

A lot of our medicines and other bioactive drugs are based on chemical structures called "enantiomers"-- molecules that are mirror images of each other and are non-superimposable. Notable among them are chiral N,N-acetals contained in diuretic drugs like bendroflumethiazide and thiabutazide, used to treat high blood pressure and edema. Because an enantiomer and its mirror image version often have different biological activities, with only one of them having pharmacological utility, an "enantioselective" or asymmetric synthesis yielding the desired enantiomer in greater amounts is highly desirable.

In the case of N,N-acetals, several studies have demonstrated their enantioselective preparation from aldehydes, aldimines, or enamines. However, in all these cases, their reaction partner has been limited to aldehyde or imines. While ketones have been employed, with instances of successful enantioselective N,N-acetal synthesis, their use--in general--is not considered effective.

In a recent study published in Advanced Synthesis & Catalysis, scientists from Nagoya Institute of Technology (NITech) and Osaka University in Japan explored this situation with an enantioselective synthesis of chiral N,N-acetals from α-dicarbonyl compounds--compounds with two carbonyl (ketone) groups on the α-carbon--in presence of chiral imidazoline phosphoric acid catalysts, and obtained yields as high as 99% with a maximum enantiopurity of 96%.

"Our study presents the first highly stereoselective formation of chiral N,N-acetals from α-ketoesters using an original catalyst that can be used for other stereoselective synthetic reactions as well," says Prof. Shuichi Nakamura from NITech, who led the study.

The scientists began by examining the reaction of 2-aminobenzamide with various α-ketoesters in presence of different catalysts. The α-ketoesters differed from one another in the nature of the functional group attached to the α-carbon, while the catalysts chosen were bis(imidazoline)-phosphoric acid with different substituents attached to the nitrogen in the imidazoline ring, mono-imidazoline-phosphoric acid, and two commercial chiral phosphoric acids. Among these various combinations, scientists found the best yield (99%) and enantiopurity (92%) in the case of α-ketoester with benzhydryl group and a bis(imidazoline)-phosphoric acid catalyst with 1-naphthalenesulfonyl group.

Scientists next examined the reaction of various aminobenzamides (bearing either an electron-donating methyl group or electron-withdrawing fluoro, chloro, and bromo groups) with different α-ketoesters (containing the same benzhydryl group but different functional groups in place of an earlier phenyl group) keeping the same bis(imidazoline)-phosphoric acid catalyst with 1-naphthalenesulfonyl group. All the combinations showed good yield (77-95%) along with high enantioselectivity (82-96%).

In addition, the team looked at the enantioselective synthesis of N,N-acetals via the reaction of N-benzyl isatin (a cyclic α-ketoamide), benzil (an acyclic diketone), and benzaldehyde with 2-aminobenzamide for the same catalyst. All three reactions yielded products with high enantiopurity (91-93%).

The team also proposed a possible mechanism for the N,N-acetal formation reaction corresponding to the best yield (99%), involving a ketimine intermediate with an amide group that helps avoid steric repulsion between the phenyl group on imidazoline, enabling the formation of an (R)-isomer with high enantiopurity.

While the mechanism is still speculative and requires further investigation, scientists are excited about the potential implications of the experimental results. "Our new method will enable the synthesis of candidate pharmaceutical drugs that are currently difficult to synthesize, and can even potentially help create and provide people with new and better medicines in the future," concludes Prof. Nakamura.

Now, those are some promising consequences to look forward to!

Not all friendships are created equal. Some friends get along; others struggle to avoid conflict. Conventional wisdom holds that the tenor of a friendship with someone who is nice differs from that with someone who is mean, such that the former discourages negative interactions whereas the latter aggravates them. Although it is logical to assume that children who are mean have friendships characterized by growing strife and that children who are nice report little of the same, these assumptions have not yet been tested in the real-world friendships of children.

Researchers from Florida Atlantic University's Charles E. Schmidt College of Science are the first to conduct a longitudinal study to examine the extent to which being "nice" (prosocial behavior) and being "mean" (relationally aggressive behavior) shape changes in friend perceptions of their relationship. Using a longitudinal framework, researchers examined over time associations between individual attributes and perceptions of relationship quality in 120 same-gender friendships among children in fourth, fifth and sixth grades.

The researchers examined whether one friend's nice and mean behaviors anticipate changes in the other friend's perceptions of relationship negativity (expressions of anger, conflict, and annoyance) across a period of one to three months. Being mean was defined as classmate reports of relational aggression, including the intentional use of exclusion and gossip to harm others. Being nice was defined as classmate reports of prosocial behavior, including providing assistance and treating others fairly. Findings from the study were published in the Journal of Research on Adolescence.

The results confirm the widespread assumption that one child's behavioral traits drive the other child's friendship experiences. Children with mean friends described increases in relationship negativity over time, whereas children with nice friends reported that relationship negativity declined. It is perhaps not surprising that relational aggression forecast greater negativity. Being mean is antithetical to expectations of how friends should behave and is likely viewed as a violation of trust. No one wants to be treated ill by a friend. Less obvious is the finding that one friend's nice behavior and forecast decreases in the other friend's perception of negativity in the relationship. Prosocial behaviors assuage hurt feelings, meet needs for support, and increase the rewards of companionship, all of which should inhibit expressions of negativity. Prosocial children may also be adept at conflict resolution, which can help them defuse problems before they erupt into conflict.

"These findings matter because friendship difficulties threaten socio-emotional adjustment in children as well as their ability to maintain friendships," said Brett Laursen, Ph.D., lead author and a professor of psychology in FAU's Charles E. Schmidt College of Science, FAU Broward Campuses. "We have long known that negative interactions with friends contribute to subsequent increases in psychological distress and difficulties at school. Friends who don't get along are soon former friends. Children who cannot seem to keep friends report increases in depression and victimization. Conversely, prosocial behaviors are tied to the ability to make new friends and keep old ones. Put simply, behavioral tendencies that threaten friendships threaten well-being. Behavioral tendencies that protect friendships promote child adjustment."

Researchers focused on the late primary and early middle school years, a period when children spend increasing amounts of time with friends and when the closeness and significance of friendships grow commensurately. They studied stable reciprocated friendships - both children nominated one another as friends at both time points. Both friends rated negativity within the friendship at each time point. Classmates rated each child in terms of their prosocial behavior and relationally aggressive behavior.

CORVALLIS, Ore. - Marching band members in leadership roles are more likely to feel discomfort in the neck and upper back than their less experienced bandmates, who in turn are more susceptible to left-hand pain and cognitive strain, a new study by Oregon State University suggests.

The findings also showed that gender had no bearing on how much discomfort a musician felt or the band member's perception of workload.

"The study really seems to indicate that a player's level of experience and role within the band are what drive how much discomfort they feel," said industrial engineer and ergonomics researcher Xinhui Zhu. "This is one of the first looks at college band members' susceptibility to musculoskeletal disorders. More research needs to be done to confirm trends in the data and provide more factors to compare, such as instrument type, but this is an important early step."

Findings were published in the journal Work.

While pleasing to both the performer and audience, playing a musical instrument is associated with the development of a range of potentially debilitating musculoskeletal disorders such as sprains, strains and arthritis, often abbreviated to MSDs; moreover, playing in front of a crowd has been to shown to increase musicians' stress and anxiety levels.

"Developing an MSD can have a huge impact on a person's life," said study co-author Robyn Wells, an OSU Honors College graduate who works as a mechanical design engineer at Sound Devices in Madison, Wisconsin. "You can end up with pain that restricts your ability to work or participate in physical events. Any task that requires the same movement again and again is a potential cause of an MSD."

Earlier studies, the researchers say, have shown that either prolonged playing over many years or intensive playing in as little as a week can lead to musculoskeletal discomfort, joint flexibility problems, a decline in playing ability or a combination of all of those. Additionally, marching band members' physical stress is high simply because they are marching.

"The risk of developing MSDs among marching band players in college settings is high," said Zhu, a former OSU College of Engineering faculty member and now an independent ergonomics consultant. "Musicians, who are also full-time students, participate in long practices, and for band players, game day is a nine-hour commitment. They carry a wide range of instruments in terms of shape, size, weight and playing positions. But to date there has not been much research about the factors that contribute to MSDs among college players."

To help close that knowledge gap, Zhu and Wells gave 70 members of the Oregon State University marching band four different surveys before and after a football game day in September 2017. The players were categorized by gender, experience level (novice or experienced) and role (leader or non-leader).

Leaders, who are typically older and have been playing longer than non-leaders, are responsible for their section of the band, in charge of teaching them the songs and everything that goes into the performance.

"The only statistically significant difference of discomfort found between the two experience levels was the left hand," Zhu said. "Novice players had significantly more discomfort than experienced players within this body part. Both groups had relatively high discomfort in the neck, shoulders, back and feet. Leaders had higher neck discomfort and upper back discomfort than non-leaders and reported an overall higher workload."

The research did not reveal reasons for the novices' left hand pain, though one possible explanation is that novices are unaccustomed to holding their instruments for an entire day as most high school band performances are shorter.

Novices and leaders alike, musicians need to be warned about the potential for small discomforts leading to musculoskeletal disease, Wells said, and designers and manufacturers of accessories like harnesses and neck straps may need to alter their products in the name of MSD prevention.

"The accessories apply a lot of stress on the neck and upper back as shown in the results of this study," she said. "This research also has broader implications, extending to any job in which someone is working long hours with awkward postures while carrying and picking up heavy objects and executing mentally demanding tasks. Through this study and others like it, new designs can be developed to help prevent MSDs."

Faster speech rate, greater intensity in the middle of the word, and falling pitch at the end of the word: that is the prosody[1] to adopt if one wants to come across as reliable and honest to one's listeners. Scientists from the Science and Technology for Music and Sound laboratory (CNRS/Ircam/Sorbonne Université/Ministère de la Culture)[2] and the Perceptual Systems Laboratory (CNRS/ENS PSL) have conducted a series of experiments[3] to understand how we decide, based on the voice, whether a speaker is honest and confident, or on the contrary dishonest and uncertain. They have also shown that this signature was perceived similarly in a number of languages (French, English, Spanish), and that it is registered "automatically" by the brain: even when participants were not judging the speaker's certainty or honesty, this characteristic sound impacted how they memorized the words. Prosody consequently conveys information on the truth-value or certainty of a proposition. Scientists are now trying to understand how speakers produce such prosody based on their intentions. This research was published on 8 February in Nature Communications.

A new process for inserting synthetic gene circuits into host cells, developed by a team of bioengineers at Arizona State University, has broad implications for improving the effectiveness of a range of disease therapies.

Synthetic biology is an interdisciplinary research field that uses engineering principles to create biological components that don't exist in the natural world. These synthetic components mimic naturally evolved organisms, but are customized to fight disease, including cancer.

A paper recently published in Nature Communications, "Winner-Takes-All Resource Competition Redirects Cascading Cell Fate Transitions," outlines how gene circuits can be reconfigured so that they do not overwhelm the host cells.

"We connect circuits together like a Lego chain and insert them into a host cell," explained lead author Xiaojun Tian, an assistant professor in the School of Biological and Health Systems Engineering at ASU. "The circuits in the chain are designed to perform different functions, but they must compete with each other for the cell's limited resources."

Competition for resources has been a challenge in the synthetic biology field since its inception 20 years ago. "We would find circumstances where one gene circuit in a chain would consume 90 percent of a host cell's available resources, leaving only 10 percent for the remaining circuit."

Tian's team devised a way to insert individual gene circuits into multiple host cells that work collectively. Each cell performs a specific function, eliminating the undesired competition for resources of any host cell. "Instead of dividing resources, each cell can perform 100 percent of its assigned workload," said Tian. "The host cells perform as a connected unit without depleting any one cell's resources - and each gene circuit becomes a winner."

The technology has broad implications for cancer treatment, with future applications for other diseases on the horizon. Ninety percent of cancer deaths are due to metastasis - the spread of cancer cells to other sites in the body. However, treatment resistance is still a major problem in cancer therapeutics.

"There are many different kinds of cells in a cancer mass," said Tian. "Some cells are responsive to chemotherapy and others are not, causing treatment resistance.

New multitasking synthetic gene circuitry configuration can be constructed to prevent the cells from metastasizing in the first place, while simultaneously making them more receptive to treatment."

Tian explains that multicellular synthetic circuits will be a much more effective way to treat cancer.

In the early months of the COVID-19 pandemic, there was an almost 80% decrease in primary care office visits in Ontario and a 56-fold increase in virtual visits, found new research in CMAJ (Canadian Medical Association Journal).

"Initial reports from primary care providers during the pandemic in both Canada and the United States showed major disruptions to care, decreased payments, challenges keeping offices functioning, lack of personal protective equipment and widespread uptake of virtual care, but we didn't know how COVID-19 had affected in-person office visits," says Dr. Rick Glazier, senior scientist at ICES, researcher at the MAP Centre for Urban Health Solutions at St. Michael's Hospital and lead author of the study.

In this study to understand the impact of the pandemic on primary care, researchers from ICES and Unity Health Toronto looked at billing information for primary care from March to July 2019 compared with March to July 2020, during the pandemic. They found that

Total primary care visits decreased by 28% from 7.66 to 5.51 per 1000 people per day

Older and sicker Ontarians experienced the smallest decline in total visits

Rural residents experienced an increase in total visits of 6.4%

Virtual care (telephone and video) made up 71.1% of all visits in 2020 compared with 1.2% billed before the pandemic

Total office visits declined abruptly in March 2020 and increased in the following months but were still lower in July 2020 than the previous year.

"Our findings are reassuring because the groups with the highest care needs, including those older than 65 and those with higher morbidity, maintained higher levels of care. At the same time, there was an overall decrease in care, and we don't know how much of that decrease was for care that could reasonably be deferred and how much was for care that was needed but missed," says Dr. Tara Kiran, senior author of the study, family doctor at St. Michael's Hospital of Unity Health Toronto and scientist at ICES.

Provincial and territorial governments are currently paying primary care physicians for telephone and video visits, although the future of this type of care after the pandemic is unknown.

"Canadians appear to be highly satisfied with virtual care and up to one-third would like virtual care to be the first point of contact after the pandemic. There is support for virtual care to be covered by employer health plans, posing challenges to continuity of care and equity, if virtual care is not publicly funded in the future," the authors write.

A new national survey of more than 2,000 Americans by The Ohio State University Wexner Medical Center finds most plan to continue many of the pandemic precautions in the name of public health, even when the pandemic is over.

As more people get vaccinated against COVID-19, there's growing optimism for a happier and healthier future. But experts warn that life will not return to normal right away, and people should expect many health precautions and restrictions implemented during the pandemic to stick around for the foreseeable future.

"While the progress we're making toward recovery is exciting, it's critical that we don't ease up on the precautions that we know have worked thus far," said Dr. Iahn Gonsenhauser, chief quality and patient safety officer at The Ohio State Wexner Medical Center. "Masks and physical distancing are still our best weapons for limiting spread and, now that we have a vaccine, will make those precautions even more effective and will drive new cases way down if we stay the course."

The survey found that nearly three-quarters (72%) of Americans plan to continue to wear masks in public, four out of five (80%) will still avoid crowds and 90% plan to keep up frequent handwashing and sanitizer use after COVID-19. Gonsenhauser says it's encouraging that people are willing to continue these practices and that this year's flu season is proof of their effectiveness.

"Flu cases and hospitalizations are way down compared to recent years. A lot of that is likely because precautions like masking, physical distancing and hand hygiene are working to prevent the flu," Gonsenhauser said. "I think a lot of people realize what we've learned from COVID-19 can be applied more generally to keep our population healthy."

After nearly a year of living in a world drastically changed by the pandemic, continuing these practices may ease the anxiety of returning to public spaces. Wearing a mask, for example, can provide a sense of control and comfort to those with lingering pandemic fears.

Experts also predict that there are some aspects of society that will never return to pre-pandemic standards, and that's not all bad. Work from home options will likely stick around in many industries and the convenience of seeing your doctor virtually through a telehealth visit is likely to remain and even expand in the future.

Researchers in South Korea have successfully developed a wearable sensor that can detect illegal drugs in sweat by using nanomaterials technology that amplify the optical signal of narcotics to a flexible, body-worn material. Led by Dr. Ho Sang Jung, the research unit is part of the Korea Institute of Materials Science(KIMS), a government-funded research institute under the Ministry of Science and ICT.

The technology enables fast and highly sensitive drug detection: the sweat patch is attached to the skin for a certain period of time and then irradiated with light for testing. It only takes one minute without requiring additional process.

Traditional drug detection process requires a complex method of extracting suspected drug components from biologic specimens including hair, blood, and urine, and then analyzing drugs through gas or liquid chromatography-mass spectrometry (GC/MS or LC/MS). It takes longer testing time and requires a large room for the instrument and skilled technicians. Although rapid kits can detect drugs in urine, they only detect a single component in a single test and have low sensitivity.

In the case of athletes, anti-doping drug testing is conducted to detect prohibited substances in blood and urine. Blood testing is often avoided due to concerns about decline in athletic performance, and urine testing may violate human rights as the tester must observe the athlete's urination. For the large sports events such as the Olympics, it is difficult to test all of the participants.

The researchers focused on sweat which is not invasive and relatively free from human rights issues. However, only small amount of substances is discharged in sweat, even though sweat contains various drugs taken so a highly sensitive sensor technology had to be developed for better detection.

The team's highly sensitive sensing utilized the surface-enhanced Raman scattering technology capable of enhancing the Raman signal of chemical substances by 1010 times and more. As the Raman scattering signal includes the specific signal of molecules, intuitive substance identification is possible no matter what drug is discharged.

The researchers paid attention to the cocoon protein, a flexible and wearable material to develop a wearable optical sensor. A silk fibroin solution, a natural protein, was extracted from silkworm cocoon to make a 160 nanometer (nm) thick film. The film was coated with 250 nanometers (nm) thick silver nanowire and transferred to the medical patch that can be attached to the skin.

Once the patch absorbs the sweat, the drug substance in the sweat penetrates the wearable sensor and reaches the silver nanowire. By irradiating the Raman laser on the patch, the drug can be detected in real time without removing the sensor.

This technology can help address social problems such as drug distribution and abuse related to celebrities, drug transactions in clubs, and the prohibited substance taken by athletes. Since the production cost is less than 50 cents per piece, it can be used for an anti-doping program as a complete enumeration survey during large sports events such as the Olympics.

Dr. Ho Sang Jung, the leader of research unit, said, "As seen in recent drug-related crimes, Korea is no longer a drug-free country. The developed technology would overcome the technological limitations on identifying drug and prohibited substance use and enable drug detection without invasive and ethical problems."