Culture

Chronic constipation (CC) remains a serious medical and social problem because the complexity of diagnosis, the lack of a single approach to treatment, and unsatisfactory treatment results. The causes of constipation are varied - from the abnormal anatomical structure of the large intestine and its location in the abdominal cavity to impaired neurohumoral regulation of its motility, endocrine pathology, psychogenic factors, poor nutrition, as well as a combination of these factors. The mechanism of the formation of the constipation syndrome, while remaining largely unclear, is of great interest as an object of research. Understanding the pathophysiological processes in constipation syndrome can be the key to improving the methods of conservative and surgical treatment. In particular, the Republican Clinical Hospital of Tatarstan has accumulated 20 years of experience in the treatment of refractory constipation.

The paper is a joint effort by Guzel Sitdikova (Chair, Department of Human and Animal Physiology, Kazan Federal University), Dina Yarullina (Associate Professor, Department of Microbiology, Kazan Federal University), Oleg Karpukhin (Professor, Department of Surgical Diseases, Kazan State Medical University), and Republican Clinical Hospital of Tatarstan.

The objective of this particular research was to gain an insight into the role of contractility and microbiota in the etiology of CC. To this end, the scientists studied spontaneous and evoked contractile activity of descending colon segments from patients that had undergone surgery for refractory forms of CC. The juxta-mucosal microbiota of these colon samples were characterized with culture-based and 16S rRNA sequencing techniques. In patients with CC, the spontaneous colonic motility remained unchanged compared to the control group without dysfunctions of intestinal motility. Moreover, contractions induced by potassium chloride and carbachol were increased in both circular and longitudinal colonic muscle strips, thus indicating preservation of contractile apparatus and increased sensitivity to cholinergic nerve stimulation in the constipated intestine. Based on the previous data, it can be suggested that smooth muscle cells develop a compensatory response to the abnormality in cholinergic stimulation. In the test group, the gut microbiota composition was assessed as being typically human, with four dominant bacterial phyla, namely Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, as well as usual representation of the most prevalent gut bacterial genera. Yet, significant inter-individual differences were revealed. The phylogenetic diversity of gut microbiota was not affected by age, sex, or colonic anatomy (dolichocolon or megacolon). The abundance of butyrate-producing genera Roseburia, Coprococcus, and Faecalibacterium was low, whereas conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased in the gut microbiomes of the constipated patients. As evidenced by the study, specific microbial biomarkers for constipation state are absent. The results point to a probable role played by the overall gut microbiota at the functional level. To the authors' knowledge, this is the first comprehensive characterization of CC pathogenesis, finding lack of disruption of motor activity of colonic smooth muscle cells and insufficiency of particular members of gut microbiota usually implicated in CC.

Treatment of patients with any pathology becomes effective if it is etiopathogenetically justified, that is, it is aimed at eliminating the etiological factors of the disease and blocking the mechanisms of the development of the disease. This pilot study of the mechanisms of the formation of CC syndrome in various anatomical anomalies of the structure and location of the colon not only expands the understanding of this complex process, but is also of clinical interest. The obtained results can contribute to the choice of the optimal variant of drug stimulation of colon motility during constipation, substantiation of radical approaches to treatment, clarification of indications for the use of probiotics or intestinal microbiota transplantation. However, for a better understanding of the pathophysiological and microbiological processes in the colon in CC syndrome with subsequent clinical use of the obtained results, additional studies are needed.

Due to the small number of observations, the results of physiological and microbiological studies do not allow generalized conclusions to be drawn about specific processes in the intestine in CC syndrome, but only reflect the specifics of refractory constipation in a group of patients with a mechanical obstacle to the movement of the chyme against the background of an abnormal anatomical structure or location of the intestine. The results indicate the preservation of the molecular mechanisms of muscle tissue contraction in patients with chronic coprostasis and its increased sensitivity to cholinergic stimulation. We consider the study of other links in the regulation of motility - the enteric and central nervous systems, Cajal cells, as well as the influence of metabolites of the intestinal microbiota on the contractile activity of smooth muscle cells - as potential directions for further research. It is also advisable to study the contractile activity of the smooth muscle of the large intestine in different age groups of patients with constipation, with congenital anomalies of the autonomic innervation of the intestine and in patients with decompensation of the motor-evacuation function of the intestine against the background of prolonged use of laxatives.

According to the study, the structure of the microbial community of the large intestine of patients mainly corresponds to the normal microflora of the human intestine. Individual members of the intestinal microbiota have been identified that are capable of influencing the motor-evacuation function of the intestine due to the produced metabolites, which confirms the presence of a functional relationship between chronic constipation and the composition of the intestinal microbiota. Nevertheless, according to modern concepts, the development of coprostasis is promoted not by individual taxa, but by the entire microbial ensemble as a whole. More observations are also needed to confirm this assumption.

Contract tracing apps used to reduce the spread of COVID-19 are unlikely to be effective without proper uptake and support from concurrent control measures, finds a new study by UCL researchers.

The systematic review*, published in Lancet Digital Health, shows that evidence around the effectiveness of automated contact tracing systems is currently very limited, and large-scale manual contact tracing alongside other public health control measures - such as physical distancing and closure of indoor spaces such as pubs - is likely to be required in conjunction with automated approaches.

The team found 15 relevant studies by reviewing more than 4,000 papers on automated and partially-automated contact tracing, and analysed these to understand the potential impact these tools could have in controlling the COVID-19 pandemic.

Lead author Dr Isobel Braithwaite (UCL Institute of Health Informatics) said: "Across a number of modelling studies, we found a consistent picture that although automated contact tracing could support manual contact tracing, the systems will require large-scale uptake by the population and strict adherence to quarantine advice by contacts notified to have a significant impact on reducing transmission."

The authors suggest that even under optimistic assumptions - where 75-80% of UK smartphone owners are using a contact tracing app, and 90-100% of identified potential close contacts initially adhere to quarantine advice - automated contact tracing methods would still need to be used within an integrated public health response to prevent exponential growth of the epidemic.

In total, 4,033 papers published between 1 Jan 2000 and 14 April 2020 were reviewed, which allowed researchers to identify 15 papers with useful data. The seven studies that addressed automated contact tracing directly were modelling studies that all focused on COVID-19. Five studies of partially-automated contact tracing were descriptive observational studies or case studies, and three studies of automated contact detection looked at a similar disease context to COVID-19, but did not include subsequent tracing or contact notification.

Partially-automated systems may have some automated processes, for instance in determining the duration of follow-up of contacts required, but do not use proximity of smartphones as a proxy for contact with an infected person.

Analysis of automated contact tracing apps generally suggested that high population uptake of relevant apps is required alongside other control measures, while partially-automated systems often had better follow-up and slightly more timely intervention.

Dr Braithwaite said: "Although automated contact tracing shows some promise in helping reduce transmission of COVID-19 within communities, our research highlighted the urgent need for further evaluation of these apps within public health practice, as none of the studies we found provided real-world evidence of their effectiveness, and to improve our understanding of how they could support manual contact tracing systems."

The review shows that, at present, there is insufficient evidence to justify reliance on automated contact tracing approaches without additional extensive public health control measures.

Dr Robert Aldridge (UCL Institute of Health Informatics) added: "We currently do not have good evidence about whether a notification from a smartphone app is as effective in breaking chains of transmission by giving advice to isolate due to contact with a case of COVID-19 when compared to advice provided by a public health contact tracer. We urgently need to study this evidence gap and examine how automated approaches can be integrated with existing contact tracing and disease control strategies, and generate evidence on whether these new digital approaches are cost-effective and equitable."

If implemented effectively and quarantine advice is adhered to appropriately, automated contact tracing may offer benefits such as reducing reliance on human recall of close contacts, which could enable identification of additional at-risk individuals, informing potentially affected people in real-time, and saving on resources.

Dr Braithwaite added: "We should be mindful that automated approaches raise potential privacy and ethics concerns, and also rely on high smartphone ownership, so they may be of very limited value in some countries. Too much reliance on automated contact tracing apps may also increase the risk of COVID-19 for vulnerable and digitally-excluded groups such as older people and people experiencing homelessness."

If implementing automated contact tracing technology, the authors say that decision-makers should thoroughly assess available evidence around its effectiveness, privacy and equality considerations, monitoring this as the evidence base evolves.

They add that plans to properly integrate contact tracing apps within comprehensive outbreak response strategies are important, and their impacts should be evaluated rigorously. A combination of different approaches is needed to control COVID-19, and the review concludes that contact tracing apps have the potential to support that but they are not a panacea.

This study is co-authored by researchers UCL Public Health Data Science Research Group, Institute of Health Informatics, Department of Applied Health Research, and Collaborative Centre for Inclusion Health.

*A systematic review carefully identifies all the relevant published and unpublished studies, rates them for quality and synthesises the studies' findings across the studies identified.

Study limitations

As part of this systematic review, researchers did not find any epidemiological studies comparing automated to manual contact tracing systems and their effectiveness in identifying contacts. Other limitations include the lack of eligible empirical studies of fully-automated contact tracing and a paucity of evidence related to ethical concerns or cost-effectiveness.

Since COVID-19 emerged late last year, there's been an enormous amount of research produced on this novel coronavirus disease. But the content publicly available for this data and the format in which it's presented lack consistency across different countries' national public health institutes, greatly limiting its usefulness, Children's National Hospital scientists report in a new study. Their findings and suggestions, published online August 19 in Science & Diplomacy, could eventually help countries optimize their COVID-19-related data -- and data for future outbreaks of other diseases -- to help further new research, clinical decisions and policy-making around the world.

Recently, explains study senior author Emmanuèle Délot, Ph.D., research faculty at Children's National Research Institute, she and her colleagues sought data on sex differences between COVID-19 patients around the world for a new study. However, she says, when they checked the information available about different countries, they found a startling lack of consistency, not only for sex-disaggregated data, but also for any type of clinical or demographic information.

"The prospects of finding the same types of formats that would allow us to aggregate information, or even the same types of information across different sites, was pretty dismal," says Dr. Délot.

To determine how deep this problem ran, she and colleagues at Children's National, including Eric Vilain, M.D., Ph.D., the James A. Clark Distinguished Professor of Molecular Genetics and the director of the Center for Genetic Medicine Research at Children's National, and Jonathan LoTempio, a doctoral candidate in a joint program with Children's National and George Washington University, surveyed and analyzed the data on COVID-19.

The research spanned data reported by public health agencies from highly COVID-19 burdened countries, viral genome sequence data sharing efforts, and data presented in publications and preprints.

At the time of study, the 15 countries with the highest COVID-19 burden at the time included the US, Spain, Italy, France, Germany, the United Kingdom, Turkey, Iran, China, Russia, Brazil, Belgium, Canada, the Netherlands and Switzerland. Together, these countries represented more than 75% of the reported global cases. The research team combed through COVID-19 data presented on each country's public health institute website, looking first at the dashboards many provided for a quick glimpse into key data, then did a deeper dive into other data on this disease presented in other ways.

The data content they found, says LoTempio, was extremely heterogenous. For example, while most countries kept running totals on confirmed cases and deaths, the availability of other types of data -- such as the number of tests run, clinical aspects of the disease such as comorbidities, symptoms, or admission to intensive care, or demographic information on patients, such as age or sex -- differed widely among countries.

Similarly, the format in which data was presented lacked any consistency among these institutes. Among the 15 countries, data was presented in plain text, HTML or PDF. Eleven offered an interactive web-based data dashboard, and seven had comma-separated data available for download. These formats aren't compatible with each other, LoTempio explains, and there was little to no documentation about where the data that supplies some formats -- such as continually updated web-based dashboards -- was archived.

Dr. Vilain says that a robust system is already in place to allow uniform sharing of data on flu genomes -- the World Health Organization's (WHO) Global Initiative on Sharing All Influenza Data (GISAID) -- which has been readily adapted for the virus that causes COVID-19 and has already helped advance some types of research. However, he says, countries need to work together to develop a similar system for harmonized sharing other types of data for COVID-19. The study authors recommend that COVID-19 data should be shared among countries using a standardized format and standardized content, informed by the success of GISAID and under the backing of the WHO.

In addition, the authors say, the explosion of research on COVID-19 should be curated by experts who can wade through the thousands of papers published on this disease since the pandemic began to identify research of merit and help merge clinical and basic science.

"Identifying the most useful science and sharing it in a way that's usable to most researchers, clinicians and policymakers, will not only help us emerge from COVID-19 but could help us prepare for the next pandemic," Dr. Vilain says.

Researchers at the University of Minnesota and University of Washington found a statistical relationship between the number of hospital beds (ICU and non-ICU) occupied by COVID-19 patients in a state and reported mortality. Published today in the Journal of General Internal Medicine, this research is believed to be the first to use actual, state-level data to examine this association.

“These estimates provide a better understanding of the projections of the COVID-19 pandemic in the U.S. especially when states are monitoring economic activities, and provide important practice insights for hospitals in terms of assessment of hospital bed and ICU bed capacity and preparedness,” said study lead Pinar Karaca-Mandic, professor and academic director of the Medical Industry Leadership Institute (MILI) in the U of M’s Carlson School of Management.

Utilizing the U of M’s COVID-19 Hospitalization Tracking Project, researchers examined data from 23 states that reported daily percentages of ICU and non-ICU-bed use by COVID-19 patients.

The study found:

COVID-19 patients occupied nearly 20% of all ICU-bed use in all states examined and about a 5% of non-ICU bed capacity;
a 1% increase in ICU-bed use (17 beds on average) was associated with 2.84 more COVID-19 deaths over the next seven days;
a 1% increase in non-ICU bed use (130 beds on average) was associated with 17.84 more COVID-19 deaths.

“ICU and non-ICU bed use as a percentage of the bed capacity of a state were significantly associated with an increase of overall COVID-19 deaths over the next seven days," explained Anirban Basu, study co-author and a professor of Health Economics and the director of The CHOICE Institute at the University of Washington. “The intensity of association for ICU-bed use was higher than non-ICU-bed use.”

The authors found that the results held true across a variety of alternate specifications.

“Most policy interventions to address the COVID-19 outbreak in the United States have focused on ‘flattening the curve’ – an approach to spread out hospitalizations over a longer duration to avoid overwhelming the healthcare system,” said Soumya Sen, associate professor and academic director of the Management Information Systems Research Center (MISRC) in the Carlson School, who co-authored the study. “The forecasting models informing these policy decisions make assumptions about the relation between the number of COVID-19 cases, hospitalizations, intensive care unit (ICU) demand, and subsequent impact on mortality.”

As this study took place during the COVID-19 pandemic, some states may have been able to expand the number of hospital beds. However, the authors note that doing so for ICU beds was likely difficult due to infrastructure constraints.

Other study authors included Dr. Archelle Georgiou, chief health officer of Starkey Hearing Technologies and an executive-in-residence with MILI at the Carlson School, as well as Yi Zhu, a doctoral student at the Information Decision Sciences department in the Carlson School.

This research was funded, in part, by the University of Minnesota Office of Academic Clinical Affairs and the United Health Foundation.

Journal

Journal of General Internal Medicine

DOI

10.1007/s11606-020-06084-7

California voters will be asked to approve a return to affirmative action on Nov. 3 with Proposition 16, which would restore the right of the state's colleges and universities to consider race, ethnicity and gender in admission decisions.

Affirmative action is a contentious issue across the globe, hotly debated in countries such as India, Sri Lanka, Malaysia, Nigeria and Brazil, as well as in the United States. While the direct effects of affirmative action on college admissions are well known, new evidence from India shows that affirmative action has indirect benefits on the behavior of underrepresented high school students, who tend to stay in school longer when they know higher education is within reach.

In a new University of California San Diego study published in the Review of Economics and Statistics, researchers find minority students attain 0.8 additional years of education where affirmative action policies are in place. The study underscores previous theoretical work on affirmative action that shows the opportunity to be admitted to college may motivate students to graduate from high school, according to the study's author, Gaurav Khanna, assistant professor of economics at UC San Diego's School of Global Policy and Strategy.

"In the policy space, people have made claims that affirmative action lowers standards and the learning gains for underrepresented students who will 'no longer work as hard.' My research suggests the opposite," Khanna said. "Affirmative action makes going to a good college much more attainable, and actually encourages minority groups to work harder to get into such schools. Without affirmative action, many colleges may not appear attainable, and it may discourage students from even trying."

India's federal government instituted affirmative action policies in 1993, reserving 27% of government jobs that are highly sought after for Other Backward Classes (OBCs)--a collective term used by the country's government to classify castes which are educationally or socially disadvantaged. In 2006, reservations in colleges were implemented.

Other research shows how these affirmative action policies in India increased the representation of minority groups in top colleges, and how the graduates went on to perform well in college and in the subsequent labor market. However, the UC San Diego study explores if affirmative action incentivizes students to stay in school by looking at the educational attainment at pre-collegiate levels.

To answer the question, Khanna compiled a number of data sources, including the Indian National Sample Survey (NSS) to map the trends in educational attainment by birth cohort and social group. Those born before 1976 would be over the age of 18 by the time the federal government policy was implemented in 1994. Thus, he looked at education levels of minority students in this cohort and compared them to education levels attained by OBCs before the affirmative action policies were enacted.

The results show that after affirmative action policies were implemented, there was a marked increase in OBCs' educational attainment. While non-minorities were still more likely to pursue more education, wide-scale affirmative action helped bridge the education gap by about 40% over a decade and a half.

"The evidence suggests that aspirations respond to such laws and additional research also shows that if peers are seen to benefit from this policy, then a role model effect may encourage educational attainment," Khanna writes.

While affirmative action is a federal law in India, each state chooses a different level of application. This is defined by the fraction of seats reserved at universities and government job openings reserved for minorities, compared to their population in that state. For example, in the state of Karnataka the policy is stronger with more seats reserved in jobs and colleges, relative to the OBC population. Conversely, in the state of Madhya Pradesh fewer jobs and college seats are reserved for OBCs, as a fraction of their population. Khanna finds that states that had a higher intensity of affirmative action, in terms of the fraction of seats reserved per OBC, saw a sharper increase in the educational attainment of minorities.

Affirmative action: a contentious policy both at home and abroad

Today, in India these policies are an integral part of political platforms and election campaigns; the media covers the policies extensively, and any policy change is met with protests from different factions.

Similarly, in the U.S., the issue is divisive. For example, the Trump administration announced in 2018 that it was abandoning the Obama administration policies that called on universities to consider race as a factor in diversifying campuses. Education Secretary Betsy DeVos stated that "schools should continue to offer equal opportunities for all students."

Given the debate in both countries, the other question Khanna sought to answer: is this educational response from the minority groups rational in terms of the expected costs and benefits?

With education levels being important for the qualification criteria for government jobs in India, Khanna found that between 2000 and 2005, the fraction of OBCs in public sector jobs rose from 22% to 27%. These jobs are extremely lucrative, especially in rural areas, where they guarantee benefits and job security. As such, increases in the likelihood of getting such jobs can greatly influence the decision made by minority groups.

Khanna writes, "Yet even for members of the minority group who do not get government jobs, an increase in education may translate into benefits (like better health) and high wages as the estimated returns to education in developing countries are between 6% and 13%."

He concluded, "Indeed, lowering educational inequalities--and possibly wealth inequalities--may be intrinsically valuable to policymakers. In light of these results, policymakers should consider the externalities of affirmative action policies when designing them."

BOSTON - In the most comprehensive study of COVID-19 pediatric patients to date, Massachusetts General Hospital (MGH) and Mass General Hospital for Children (MGHfC) researchers provide critical data showing that children play a larger role in the community spread of COVID-19 than previously thought. In a study of 192 children ages 0-22, 49 children tested positive for SARS-CoV-2, and an additional 18 children had late-onset, COVID-19-related illness. The infected children were shown to have a significantly higher level of virus in their airways than hospitalized adults in ICUs for COVID-19 treatment.

"I was surprised by the high levels of virus we found in children of all ages, especially in the first two days of infection," says Lael Yonker, MD, director of the MGH Cystic Fibrosis Center and lead author of the study, "Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Reponses," published in the Journal of Pediatrics. "I was not expecting the viral load to be so high. You think of a hospital, and of all of the precautions taken to treat severely ill adults, but the viral loads of these hospitalized patients are significantly lower than a 'healthy child' who is walking around with a high SARS-CoV-2 viral load."

Transmissibility or risk of contagion is greater with a high viral load. And even when children exhibit symptoms typical of COVID-19, like fever, runny nose and cough, they often overlap with common childhood illnesses, including influenza and the common cold. This confounds an accurate diagnosis of COVID-19, the illness derived from the SARS-CoV-2 coronavirus, says Yonker. Along with viral load, researchers examined expression of the viral receptor and antibody response in healthy children, children with acute SARS-CoV-2 infection and a smaller number of children with Multisystem Inflammatory Syndrome in Children (MIS-C).

Findings from nose and throat swabs and blood samples from the MGHfC Pediatric COVID-19 Biorepository carry implications for the reopening of schools, daycare centers and other locations with a high density of children and close interaction with teachers and staff members. "Kids are not immune from this infection, and their symptoms don't correlate with exposure and infection," says Alessio Fasano, MD, director of the Mucosal Immunology and Biology Research Center at MGH and senior author of the manuscript. "During this COVID-19 pandemic, we have mainly screened symptomatic subjects, so we have reached the erroneous conclusion that the vast majority of people infected are adults. However, our results show that kids are not protected against this virus. We should not discount children as potential spreaders for this virus."

The researchers note that although children with COVID-19 are not as likely to become as seriously ill as adults, as asymptomatic carriers or carriers with few symptoms attending school, they can spread infection and bring the virus into their homes. This is a particular concern for families in certain socio-economic groups, which have been harder hit in the pandemic, and multi-generational families with vulnerable older adults in the same household. In the MGHfC study, 51 percent of children with acute SARS-CoV-2 infection came from low-income communities compared to 2 percent from high-income communities.

In another breakthrough finding from the study, the researchers challenge the current hypothesis that because children have lower numbers of immune receptors for SARS-CoV2, this makes them less likely to become infected or seriously ill. Data from the group show that although younger children have lower numbers of the virus receptor than older children and adults, this does not correlate with a decreased viral load. According to the authors, this finding suggests that children can carry a high viral load, meaning they are more contagious, regardless of their susceptibility to developing COVID-19 infection.

The researchers also studied immune response in MIS-C, a multi-organ, systemic infection that can develop in children with COVID-19 several weeks after infection. Complications from the accelerated immune response seen in MIS-C can include severe cardiac problems, shock and acute heart failure. "This is a severe complication as a result of the immune response to COVID-19 infection, and the number of these patients is growing," says Fasano, who is also a professor of Pediatrics at Harvard Medical School (HMS). "And, as in adults with these very serious systemic complications, the heart seems to be the favorite organ targeted by post-COVID-19 immune response," adds Fasano.

Understanding MIS-C and post-infectious immune responses from pediatric COVID-19 patients is critical for developing next steps in treatment and prevention strategies, according to the researchers. Early insights into the immune dysfunction in MIS-C should prompt caution when developing vaccine strategies, notes Yonker.

As MGHfC pediatricians, both Yonker and Fasano are constantly fielding questions from parents about the safe return of their children to school and daycare. They agree that the most critical question is what steps the schools will implement "to keep the kids, teachers, and personnel safe." Recommendations from their study, which includes 30 co-authors from MGHfC, MGH, HMS, Massachusetts Institute of Technology, Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, include not relying on body temperature or symptom monitoring to identify SARS-CoV-2 infection in the school setting.

The researchers emphasize infection control measures, including social distancing, universal mask use (when implementable), effective hand-washing protocols and a combination of remote and in-person learning. They consider routine and continued screening of all students for SARS-CoV-2 infection with timely reporting of the results an imperative part of a safe return-to-school policy.

"This study provides much-needed facts for policymakers to make the best decisions possible for schools, daycare centers and other institutions that serve children," says Fasano. "Kids are a possible source of spreading this virus, and this should be taken into account in the planning stages for reopening schools."

Fasano fears that a hurried return to school without proper planning could result in an uptick in cases of COVID-19 infections. "If schools were to reopen fully without necessary precautions, it is likely that children will play a larger role in this pandemic," the authors conclude.

Most effort in origins of life research is focused on understanding the prebiotic formation of biological building blocks. However, it is possible early biological evolution relied on different chemical structures and processes, and these were replaced gradually over time by aeons of evolution. Recently, chemists Irena Mamajanov, Melina Caudan and Tony Jia at the Earth-Life Science Institute (ELSI) in Japan borrowed ideas from polymer science, drug delivery, and biomimicry to explore this possibility. Surprisingly, they found that even small highly branched polymers could serve as effective catalysts, and these may have helped life get started.

In modern biology, coded protein enzymes do most of the catalytic work in cells. These enzymes are made up of linear polymers of amino acids, which fold up and double-back on themselves to form fixed three-dimensional shapes. These preformed shapes allow them to interact very specifically with the chemicals whose reactions they catalyse. Catalysts help reactions occur much more quickly than they would otherwise, but don't get consumed in the reaction themselves, so a single catalyst molecule can help the same reaction happen many times. In these three-dimensional folded states, most of the structure of the catalyst doesn't directly interact with the chemicals it acts on, and just helps the enzyme structure keep its shape.

In the present work, ELSI researchers studied hyperbranched polymers - tree-like structures with a high degree and density of branching which are intrinsically globular without the need for informed folding - which is required for modern enzymes. Hyperbranched polymers, like enzymes, are capable of positioning catalysts and reagents, and modulating local chemistry in precise ways.

Most effort in origins of life research is focused on understanding the prebiotic formation of modern biological structures and building blocks. The logic is that these compounds exist now, and thus understanding how they could be made in the environment might help explain how they came to be. However, we only know of one example of life, and we know that life is constantly evolving, meaning that only the most successful variants of organisms survive. Thus it may be reasonable to assume modern organisms may not be very similar to the first organisms, and it is possible prebiotic chemistry and early biological evolution relied on different chemical structures and processes than modern biology to reproduce itself. As an analogy with technological evolution, early cathode-ray TV sets performed more or less the same function as modern high definition displays, but they are fundamentally different technologies. One technology led to the creation of the other in some ways, but it was not necessarily the logical and direct precursor of the other.

If this kind of 'scaffolding' model for biochemical evolution is true, the question becomes what sort of simpler structures, besides those used in contemporary biological systems, might have helped carry out the same sorts of catalytic functions modern life requires? Mamajanov and her team reasoned that hyperbranched polymers might be good candidates.

The team synthesised some of the hyperbranched polymers they studied from chemicals which could reasonably be expected to have been present on early Earth before life began. The team then showed that these polymers could bind small naturally occuring inorganic clusters of atoms known as zinc sulfide nanoparticles. Such nanoparticles are known to be unusually catalytic on their own.

As lead scientist Mamajanov comments, 'We tried two different types of hyperbranched polymer scaffolds in this study. To make them work, all we needed to do was to mix a zinc chloride solution and a solution of polymer, then add sodium sulfide, and "voila," we obtained a stable and effective nanoparticle-based catalyst.'

The team's next challenge was to demonstrate that these hyperbranched polymer-nanoparticle hybrids could actually do something interesting and catalytic. They found that these metal sulfide doped polymers that degrade small molecules were especially active in the presence of light, in some cases they catalysed the reaction by as much as a factor of 20. As Mamajanov says, 'So far we have only explored two possible scaffolds and only one dopant. Undoubtedly there are many, many more examples of this remaining to be discovered.'

The researchers further noted this chemistry may be relevant to an origins of life model known as the 'Zinc World'. According to this model, the first metabolism was driven by photochemical reactions catalysed by zinc sulfide minerals. They think that with some modifications, such hyperbranched scaffolds could be adjusted to study analogues of iron or molybdenum-containing protein enzymes, including important ones involved in modern biological nitrogen fixation. Mamajanov says, 'The other question this raises is, assuming life or pre-life used this kind of scaffolding process, why did life ultimately settle upon enzymes? Is there an advantage to using linear polymers over branched ones? How, when and why did this transition occur?'

The majority of today's plant-based food is a product of plant breeding. U.S. public plant breed-ing programs often focus on crops that are important to society but may be less profitable than crops that drive the bottom line for large businesses. Studies over recent decades have reported a reduction in capacity of such programs.

A survey of 278 public sector plant breeding programs in 44 U.S. states, led by the U.S. Plant Breeding Coordinating Committee, was reported recently in an article published in Crop Sci-ence.

Programs reported significantly declining personnel hours, with many reporting that budget shortfalls or uncertainty "endangered or severely constrained" their ability to support key per-sonnel, infrastructure and operations, and access to technology. Graduate student and postdoc positions were typically the most at risk, impacting the pipeline of future breeders into both public and private sectors. Almost half of program leaders were nearing retirement age.

Public plant breeding programs are at risk of disappearing without reinvigorated, stable, long-term access to funding, technology, knowledge, and expertise. If the trajectory of declining budgets and reduced staffing and expertise in public plant breeding continues, U.S. plant breed-ing capacity as a whole (both public and private) and, more broadly, U.S. food security, natural resource resilience, and public health will erode.

Adapted from Coe, MT, Evans, KM, Gasic, K, Main, D. Plant breeding capacity in U.S. public institutions. Crop Science. 2020; 1- 13.

Unsustainable trade of species is a major pathway for the introduction of invasive alien species at distant localities and at higher frequencies. It is also a major driver of over-exploitation of wild native populations. In a new study, published in the peer-reviewed open-access scholarly journal Neobiota, scientists estimated the desire of Australians to own non-native and/or illegal alien pets and the major trends in this practice. In addition, the team suggests ways to improve biosecurity awareness in the country.

Over the last two decades, Australia has been experiencing an increased amount of non-native incursions from species prominent in the international pet trade, such as rose-ringed parakeets, corn snakes and red-eared sliders. On many occasions, these animals are smuggled into the country only to escape or be released in the wild.

In general, the Australian regulations on international pet trade are highly stringent, in order to minimise biosecurity and conservation risks. Some highly-desirable species represent an ongoing conservation threat and biosecurity risk via the pet-release invasion pathway. However, lack of consistent surveillance of alien pets held, legally or otherwise, in Australia remains the main challenge. While there are species which are not allowed to be imported, they are legal for domestic trade within the country. Pet keepers have the capacity to legally or illegally acquire desired pets if they are not accessible through importation, and the number of such traders is unquantified.

Since keeping most of the alien pets in Australia is either illegal or not properly regulated, it is really difficult to quantify and assess the public demand for alien wildlife.

"We obtained records of anonymous public enquiries to the Australian Commonwealth Department of Agriculture, Water and the Environment relating to the legality of importation of various alien taxa. We aimed to investigate whether species desired in Australia were biased towards being threatened by extinction, as indicated by broader research on pet demand or towards being invasive species elsewhere, which would indicate trade-related biosecurity risks", shares the lead author Mr. Adam Toomes from the University of Adelaide.

According to the research team's analysis, pets desired by Australians are significantly biased towards threatened species, invasive species and species prominent in the U.S. pet trade.

"This novel finding is of great concern for biosecurity agencies because it suggests that a filtering process is occurring where illegally smuggled
animals may already be "pre-selected" to have the characteristics that are correlated with invasive species," warns Mr. Adam Toomes.

However, the bias towards species already traded within the U.S. suggests that there is potential to use this as a means of predicting future Australian desire, as well as the acquisition of pets driven by desire. Future research from the Invasion Science & Wildlife Ecology Group at The University of Adelaide will investigate whether Australian seizures of illegal pets can be predicted using U.S. trade data.

SALT LAKE CITY -- Self-collected saliva and deep nasal swabs collected by healthcare providers are equally effective for detecting SARS-CoV-2, the virus that causes COVID-19, according to a new study conducted by ARUP Laboratories and University of Utah (U of U) Health.

The study, published in the Journal of Clinical Microbiology, represents one of the largest prospective specimen type comparisons to date, said Julio Delgado, MD, MS, ARUP chief medical officer. Other studies, including one from the Yale School of Public Health, have reached similar conclusions but with markedly fewer patients and specimens.

Researchers also found that specimens self-collected from the front of the nose are less effective than deep nasal swabs for virus detection. This finding prompted a subsequent study that has not yet been published in which researchers learned they could improve the sensitivity of anterior nasal swab testing to 98% by combining an anterior nasal swab with a swab collected from the back of the throat.

The results have important implications for patients and providers. The collection process for saliva and anterior nasal specimens is less invasive than the deep nasal, or nasopharyngeal, swab. In addition, both specimen types can be self-collected, reducing the risk of exposure for healthcare workers who collect nasopharyngeal specimens, said Kimberly Hanson, MD, MPH, section chief of clinical microbiology at ARUP and the primary author of the study.

"Saliva and nasal swab self-collection can resolve many of the resource and safety issues involved in SARS-CoV-2 diagnostic testing," Delgado said.

ARUP and U of U Health anticipate being able to start offering testing on saliva in some U of U Health clinical settings in early September. They already are using anterior nasal swabs in combination with throat swabs to test some asymptomatic individuals.

COVID-19 testing on these alternatives to nasopharyngeal swabs will increase with time, Delgado said. "From the start of the COVID-19 pandemic, ARUP has worked to build capacity for high-quality COVID-19 testing," he said. "Our goal is to make this testing available to hospitals and healthcare systems nationwide."

Hanson and her colleagues analyzed more than 1,100 specimens from 368 volunteers at the U of U Health Redwood Health Center drive-through testing site from late May through June. Volunteers self-collected saliva that they spit into a tube and swabbed from the front of both nostrils to produce specimens for testing. The researchers compared test results from these specimen types with test results from nasopharyngeal swabs healthcare providers collected from the volunteers. Discrepant results across specimens collected from the same patient triggered repeat testing using a second polymerase chain reaction (PCR)-based platform.

The study showed that SARS-CoV-2 was detected in at least two specimen types in 90% of the patients who tested positive for the virus.

As a standalone alternative specimen to nasopharyngeal swabs, saliva proved to be an excellent option, Hanson said. Positivity rates for saliva specimens were nearly the same as those for nasopharyngeal specimens.

The research showed that self-collected nasal swabs, when used alone, can miss nearly 15% of infections, which prompted researchers' further study combining them with oropharyngeal, or throat swabs.

The research is an example of how ARUP and U of U Health continue to explore new methods to serve patients and the community as well as keep healthcare workers safe, said Richard Orlandi, MD, chief medical officer for ambulatory health at U of U Health. "We appreciate the researchers at ARUP, as well as the staff and patients at our Redwood testing center who have participated in this discovery," he said. "This exciting advance reflects ARUP's and U of U Health's innovative spirit and the benefits of our partnership."

Boston, MA - Widespread layoffs amid the COVID-19 pandemic threaten to cut off millions of people from their employer-sponsored health insurance plans. But the Affordable Care Act (ACA) will protect many of these people and their families from losing coverage, according to a new study.

The Perspective article in the New England Journal of Medicine, co-authored by Harvard University PhD student Sumit Agarwal (also of Brigham and Women's Hospital) and Benjamin Sommers, professor of health policy and economics at Harvard T.H. Chan School of Public Health, will be published online August 19, 2020.

To quantify the ACA's effect on changes in health insurance coverage after job loss, the researchers looked at data from the U.S. Department of Health and Human Services' Medical Expenditure Panel Survey, a set of large-scale surveys of families and individuals, their medical providers, and employers across the U.S. The analysis compared the trajectories of 1,350 adults who lost their jobs before 2014--the year that the ACA's Medicaid and marketplace provisions, aimed at increasing health insurance coverage, went into effect--with the trajectories of 1,103 adults who lost their jobs in 2014 or later. The researchers examined the insurance status of these participants during the first three months and the last three months that they were surveyed.

Between 2011 and 2013, job loss was associated with an average health insurance coverage loss of 4.6 percentage points, the analysis found. The proportion of participants with any coverage decreased from 66.3% to 61.7%.

But after the ACA went into effect--when the overall coverage rate was much higher to begin with (76.2%)--job loss was no longer linked to an increase in the uninsured rate. Large gains in Medicaid (8.9 percentage points) and marketplace coverage (2.6 percentage points) nearly fully offset the reduction in employer-sponsored insurance for people who left or lost their job, according to the authors. Overall, the implementation of the ACA was associated with a 6.0-percentage-point net increase in the likelihood of having coverage after a job loss.

"These results indicate the critical role that the ACA will play in alleviating coverage losses related to the Covid-associated recession," the authors wrote.

The authors noted that insurance coverage gaps remain even with the ACA, and that the law's future is still uncertain amid a Supreme Court challenge from 18 Republican state attorneys general and the Trump administration, who are arguing that the law is unconstitutional.

"In the current context of millions of Americans losing their jobs and an ongoing pandemic, overturning the ACA would most likely be devastating to patients, clinicians, hospitals, and state economies," the authors wrote. "The very virus that has brought about record unemployment levels is the same agent that makes health insurance--and the new options created under the ACA--more important than ever."

Gastric bypass surgery is the most effective therapy to treat or reverse type 2 diabetes in severely obese patients. Many achieve remission of diabetes following surgery and no longer require diabetes medications. This observation has led to the theory that gastric bypass surgery has unique, weight loss-independent effects in treating diabetes, but this has remained a longstanding question in the field. Now, new research from Washington University School of Medicine in St. Louis indicates that weight loss after surgery, rather than the surgery itself, drives metabolic improvements, such as the remission of diabetes.

The researchers studied severely obese patients with diabetes who had gastric bypass surgery and then lost 18% of their body weight. In a patient who weighs 250 pounds, for example, that would be 45 pounds. The investigators compared those patients with others who also were severely obese with diabetes but had lost the same percentage of body weight through diet alone.

After reaching their weight-loss goals, members of both groups experienced similar improvements in metabolism -- such as lower blood sugar levels throughout the day, better insulin action in the liver, muscle and fat tissue, and reductions in the need for insulin and other diabetes medications. Since the group that lost weight through diet alone did just as well as the surgery group, the researchers concluded the improvements were due to weight loss alone, rather than to any physiological changes that resulted from the surgery itself.

The study is published August 20 in The New England Journal of Medicine.

"It has been presumed that gastric bypass surgery has therapeutic, metabolic effects that result in better glucose control and even remission of diabetes beyond the effects expected from weight loss alone," said principal investigator Samuel Klein, MD, director of Washington University's Center for Human Nutrition. "But we found gastric bypass surgery improves metabolic function by causing weight loss. There were no differences in the reduction of diabetes medications or in the rate of diabetes remission between surgery patients and those who lost equivalent amounts of weight through diet alone."

More than 40% of adult Americans are obese, and close to one in 10 is severely obese. Each year more than 250,000 people in the U.S. undergo bariatric surgery to help them lose weight. The gold standard procedure, called Roux-en-Y gastric bypass, has been the most successful operation in terms of total weight loss and long-term maintenance.

In this procedure, surgeons working laparoscopically use part of a patient's football-size stomach to create a pouch the size of a ping pong ball that is connected directly to the the small intestine, bypassing much of the upper portion of the small intestine. In this study, the gastric bypass procedures were performed by bariatric surgeons, J. Chris Eagon, MD, an associate professor of surgery, and Shaina R. Eckhouse, MD, an assistant professor of surgery.

Klein's team compared 11 gastric bypass surgery patients who had diabetes with 11 others who had diabetes and achieved equivalent weight loss with diet alone. The average age of patients in the diet group was about 55, while the average in the surgery group was 49. Those in the surgery group lost an average of 51 pounds, while those in the diet group lost an average of 48 pounds. All study patients maintained that weight loss for several weeks before follow-up studies were performed.

Over a 24-hour period, the researchers used sophisticated techniques in a hospital setting to measure study subjects' metabolic responses to meals. They measured insulin sensitivity in the liver, in fat tissue and in muscle tissue. They also analyzed the response of insulin-secreting beta cells in the pancreas and blood fatty acid concentrations, all of which contribute to the development of type 2 diabetes.

"It has been suggested that weight loss induced by gastric bypass surgery is different from weight loss induced by a low-calorie diet, based on the fact that certain factors -- such as increased bile acid concentrations, decreased branched-chain amino acid concentrations and alterations in the gut microbiome -- are different in surgery patients and may be responsible for the unique therapeutic effects of gastric bypass surgery," Klein said. "We found all of those factors were, in fact, different after weight loss in surgery patients than in patients who lost weight through diet alone. Yet those changes were not associated with any physiologically or clinically important metabolic benefits."

According to Klein, also the William H. Danforth Professor of Medicine and Nutritional Science and chief of the Division of Geriatrics and Nutritional Science, the loss of weight is the reason for improvements in metabolic function and reversal of diabetes. Weight loss through dieting produces the same beneficial metabolic effects as weight loss following surgery.

In an accompanying editorial in the journal about the paper, researchers from Tufts University, Harvard University, Massachusetts General Hospital and the University of Maine write that the study "delivers a straightforward and important message for both clinicians and patients -- reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes."

"However, losing 18% of body weight with diet therapy alone is extraordinarily difficult and unrealistic for most people with obesity," Klein explained. "In contrast, gastric bypass surgery leads to marked and sustained long-term weight loss, which makes it a potent therapy for people with diabetes."

Klein's study was focused on the effects of gastric bypass surgery on metabolic function, and did not look at other medical complications associated with obesity.

"Our study does not exclude the possibility that gastric bypass surgery has unique weight loss-independent effects on important clinical outcomes such as arthritis, lung function or cancer risk, which were not assessed. But when it comes to metabolic health, gastric bypass surgery is effective because it causes weight loss," he said.

A study involving older adults with pre-existing major depressive disorder living in Los Angeles, New York, Pittsburgh, and St Louis found no increase in depression and anxiety during the COVID-19 pandemic.

Researchers from five institutions, including UCLA, found that the older adults, who were already enrolled in ongoing studies of treatment resistant depression, also exhibited resilience to the stress of physical distancing and isolation. The findings were published in peer-reviewed journal, The American Journal of Geriatric Psychiatry.

"We thought they would be more vulnerable to the stress of COVID because they are, by CDC definition, the most vulnerable population," said Helen Lavretsky, MD, a professor-in-residence of psychiatry and biobehavioral sciences at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. "But what we learned is that older adults with depression can be resilient. They told use that coping with chronic depression taught them to be resilient"

For the study, researchers conducted interviews with the participants, all of whom were over the age of 60, with an average age of 69, during the first two months of the pandemic. Using two screening assessments of depression and anxiety, PHQ-9 and PROMIS, researchers found no changes in the participants' depression, anxiety or suicidality scores before and during the pandemic.

Researchers further determined that:

Participants were more concerned about the risk of contracting the virus than the risks of isolation.

While all maintained physical distance, most did not feel socially isolated and were using virtual technology to connect with friends and family.

While they were coping, many participants said their quality of life was lower, and they worry their mental health will suffer with continued physical distancing.

Participants were upset by the inadequate governmental response to the pandemic.

Based on the findings, the study authors wrote that policies and interventions to provide access to medical services and opportunities for social interaction are needed to help older adults maintain mental health and quality of life as the pandemic continues.

Lavretsky said many participants reported their quality of life to be lower, and they worried that their mental health will suffer with continued physical distancing. She said further research is needed to determine the impact of the pandemic over time.

She added that the findings offer takeaways for others while weathering the pandemic. "These older persons living with depression have been under stress for a longer time than many of the rest of us. We could draw upon their resilience and learn from it."

The study identified several self-care and coping strategies used by the participants, which included maintaining regular schedules; distracting themselves from negative emotions with hobbies, chores, work or exercise; and using mindfulness to focus on immediate surroundings and needs without thinking beyond the present.

The authors further emphasized that access to mental health care and support groups, and continued social interaction are needed to help older adults whether the pandemic.

CORVALLIS, Ore. - Policy reforms and technological improvements could drive seafood production upward by as much as 75% over the next three decades, research by Oregon State University and an international collaboration suggests.

The findings, published today in Nature, are important because by 2050 the Earth will have an estimated 9.8 billion human mouths to feed, a 2 billion increase in population from 2020. Seafood has the potential to meet much of the increased need for protein and nutrients, researchers say.

Marine ecologist Jane Lubchenco, university distinguished professor in the OSU College of Science, joined scientists from the United States, China, Chile, Mexico, Japan, South Africa, Spain, Norway, Argentina and Malaysia in analyzing how much food the ocean could be expected to sustainably produce 30 years from now.

Examining the sea's primary food-producing sectors - wild fisheries and the mariculture of finfish such as tuna and snapper as well as bivalves like clams and oysters - the researchers determined estimates of "sustainable supply curves" that take into consideration ecological, economic, regulatory and technological limitations. Mariculture means cultivating marine organisms for food and other products in coastal seawater environments or the open ocean.

The scientists framed those supply curves against future demand scenarios to predict how much food the ocean, which presently accounts for just 17% of the animal production industry, could supply as the global population swells.

"As mariculture technology improves and policies surrounding the ocean and its resources are reformed, food from the sea could increase by between 21 million and 44 million metric tons annually," said Lubchenco, a former administrator of the National Oceanic and Atmospheric Administration. "Those increases amount to between 12% and 25% of the estimated animal protein increases needed to feed the almost 10 billion people expected to live on the Earth in 2050. Rising incomes and shifts in food preferences will greatly increase demand for nutritious food in the coming decades, and the ocean can be a big part of meeting that demand."

Producing more and more food from land-based crops is challenging because of declining yield rates and competition for land and water, Lubchenco notes, as well as various environmental and health concerns associated with large-scale agriculture.

And while land-derived seafood - freshwater aquaculture and inland fisheries - plays an important role in the global food picture, its expansion faces some of the same hurdles and causes some of the same problems.

"Land-based sources of fish and other foods are certainly part of the solution, but we show that sustainable food from the sea can play a major role in global food supply and food security as well," Lubchenco said. "Stories of overfishing, pollution and unsustainable mariculture give the impression that it is impossible to sustainably increase the supply of food from the sea. But unsustainable practices, regulatory barriers and other constraints may be limiting seafood production - meaning shifts in policies and practices could benefit both conservation and food production. We've seen, for example, how changes in policy in U.S. fisheries resulted in significantly reducing overfishing and rebuilding wild stocks, thus increasing the abundance of fish in U.S. waters as well as fishery yields."

Lubchenco and colleagues including lead author Christopher Costello of the University of California, Santa Barbara, describe four primary routes to sustainably increasing ocean-based food production: Better management of wild fisheries, which account for 80% of the sea's meat production; reforms for policies governing mariculture; improvements in feeds used in mariculture; and shifts in demand to drive increased production from all ocean food sectors.

Nutritionally diverse and less environmentally burdensome than land-based food production, seafood is uniquely positioned to help feed the Earth's growing population, Lubchenco said. And directing resources away from subsidies that enhance fishing capacity toward building institutional and technical capacity for fisheries research, management and enforcement will be a key step.

"The potential for increased global production from wild fisheries hinges on maintaining fish populations near their most productive levels," Lubchenco said. "For overfished stocks, that means adopting or improving management practices that prevent overfishing and allow depleted stocks to rebuild."

Seventy-five percent of mariculture production requires some feed inputs, like fishmeal and fish oil, derived from wild forage fisheries. But alternatives like terrestrial plant- or animal-based proteins, seafood processing waste, microbial ingredients, insects, algae and genetically modified plants are in the works - innovations that could decouple mariculture from wild fisheries.

And the largest potential for expansion of food from the sea will come from the farming of bivalves.

"We have shown that the sea can be a much larger contributor to sustainable food production than is currently the case, via a collection of plausible and actionable mechanisms," Lubchenco said.

A new analysis published in Public Administration found that student graduation rates improve as more faculty employed by a college or university share sex and race/ethnic identities with students.

The analysis focuses on the concept of intersectionality, which seeks to understand how aspects of a person's social and political identities--such as gender, race, class, sexuality, ability, and physical appearance--may combine to create aspects of discrimination and privilege.

The findings demonstrate an opportunity to help marginalized students: by hiring faculty with shared intersectional identities.

"We are the first study to show how the intersectional identity of the representative can improve the outcomes of the represented," said author Daniel L. Fay, MPA, PhD, of Florida State University. "Studies of representation should not overlook the importance of intersectional representation. Women or men of color serving as elected officials, political appointees, and managers can best represent and improve the outcomes for women or men of color, respectively.

Dr. Fay noted that future studies should look beyond race/ethnicity and sex to examine the effects of the intersection of other identities.