Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Clever pest control? The role of cognition in biological pest regulation.

Crop pest management is a global challenge. Increases in agricultural intensity due to anthropogenic demands, alongside the need to reduce the reliance on pesticides to minimize environmental harm, have resulted in an urgent need to improve and expand other methods of pest control. One increasingly utilized method is biological pest control, in which natural pest predators are used to regulating crop pests. Current approaches to biological pest regulation assess the importance of a pest controller by examining its ability to maintain pest populations over an extended period. However, this approach lacks efficiency, specificity, and efficacy because it does not take into account crucial factors which determine how predators find, evaluate and remember food sources-the cognitive processes underlying their behavior. This review will investigate the cognitive factors involved in biological pest control and examine how these factors may be manipulated to impact pest behavior and pest controller performance.

COVID-19-related anxiety and trauma symptoms predict decreases in body image satisfaction in children.

The present study investigated short-term longitudinal effects of COVID-19-related trauma and separation, social, and generalized anxiety symptoms on children's body image satisfaction. Participants were 247 Canadian children (121 boys, 123 girls) aged between 7 and 12 years (M = 9.04). Two cohorts of parents were recruited to complete a questionnaire at two time points on their children's body image satisfaction and COVID-19-related trauma and anxiety symptoms. The first cohort (n = 136 children) was recruited in Summer 2020 and the second cohort (n = 111 children) was recruited in Winter 2021. For each cohort, follow-up surveys were completed approximately five months later, therefore covering an entire year with both cohorts. Multilevel regression analyses showed that children's trauma and anxiety at Time 1 predicted significant decreases in body image satisfaction at Time 2. Older children were especially at risk of decreased body image satisfaction as a result of their COVID-19-related trauma, social anxiety and generalized anxiety symptoms. Younger girls were susceptible to decreased body image satisfaction as a result of their separation anxiety symptoms. Given that children's body image dissatisfaction is a precursor to the development of eating disorders, these findings shed light on potential targets for early intervention with children who are at-risk of developing such difficulties.

Gender Disparity in Academic Gastroenterology: Beginning of the End of the Underrepresentation of Women?

BACKGROUND: Though there are an increasing number of female medical graduates, women remain underrepresented in academic medicine. There have been several reasons to explain this gender disparity, including marital status, number of children, number of hours worked, job flexibility, perceptions of women as inferior leaders, gender bias, sexual harassment, and unsupportive academic climates. AIMS: This study aimed to investigate the relationship between scholarly productivity and the representation of female gastroenterologists in academia. Specifically, scholarly productivity measured by the h-index and academic rank were explored to determine if there were gender disparities in academic productivity and rank in gastroenterology. METHODS: Gastroenterology departmental listings were obtained from the Fellowship and Residency Interactive Database of the American Medical Association. The Scopus database was used to record each physician's h-index. Statistical analyses were conducted with Wilcoxon rank-sum test, which compared matched samples by academic rank, and ANOVA tests, which compared multiple academic ranks. RESULTS: Out of 1703 academic gastroenterologists, women account for 25% of academic physicians. Women have statistically lower h-indices at the level of Assistant Professor (p = 0.0012), and at the level of Chair (p = 0.01). There was no difference in h-indices between male and female at the rank of Associate Professor and Professor. CONCLUSIONS: While these results mirror patterns appreciated in other fields of medicine, the results at the rank of Chair may suggest that despite the lower h-index compared to their male counterparts, females are perceived as having strong inherent leadership skills outside of academic productivity that are also conducive to leading a department and may be contributing to their rise to Chair.

Construction of 5-(Alkylamino)-6-aryl/alkylpyrazine-2,3-dicarbonitriles via the One-Pot Reaction of Alkyl Isocyanides with Aryl/Alkyl Carbonyl Chlorides and Diaminomaleonitrile: Fluorescence and Antimicrobial Activity Evaluation.

5-(Alkylamino)-6-aryl/alkylpyrazine-2,3-dicarbonitriles were successfully synthesized in good to moderate yields by reacting alkyl isocyanides with aryl/alkyl carbonyl chlorides, followed by the addition of diaminomaleonitrile. The synthesized pyrazines were fully characterized in this investigation, and X-ray crystal structure analysis was performed on some derivatives. The antibacterial and antifungal activities of the newly synthesized pyrazine-2,3-dicarbonitriles were assessed in addition to their UV and fluorescence results. All the compounds showed similar UV-Vis spectral features with absorption peaks (λmax) around 267, 303, and 373 nm.

Synthesis and characterization of novel tricyanofuran hydrazone probe: solvatochromism, density-functional theory calculation and selective fluorescence, and colorimetric determination of iron (III).

A tricyanofuran hydrazone (TCFH) spectroscopic probe was produced to visually recognize Fe(III) ions in aqueous environments. The synthesis was started by reacting tricyanofuran with 4-aminophenol diazonium chloride. All the synthesized compounds were characterized by spectroscopic analyses. TCFH showed distinctive solvatochromic behaviour in various organic polar solvents due to intramolecular charge transfer. Its behaviour towards sensing Fe(III) was studied using ultraviolet-visible spectrophotometry. The sensing behaviours of the proposed probe for other metal ions, namely Co(II), Cr(III), Mg(II), Pb(II), Cd(II), Ba(II), Hg(II), Mn(II), Ni(II), Cu(II), Zn(II), Ca(II), Al(III), Na(I) and K(I), were also investigated, but no spectral changes were observed, indicating the probe's potential use as a highly selective and Fe(III)-sensitive colorimetric and fluorescent chemical sensor. The TCFH probe using EtOH/H2 O (5:1; v/v) served as a colorimetric and fluorescent chemosensor for identification of Fe(III) by the naked eye owing to both its high sensitivity and selectivity towards Fe(III) compared with the other examined metal ions. The proposed TCFH probe can therefore be utilized as an effective spectroscopic sensor for Fe(III). Both colorimetric and fluorescence recognition of the analyte depended on the concentration of Fe(III) ions and was accomplished at a pH of 7. A rapid colour change from yellow to red occurred when an aqueous solution of Fe(III) ions was added. The intensity of the colour increased at higher Fe(III) concentrations. Cyclic voltammetry measurements in the dimethylformamide solvent indicated a nonreversible redox potential. This study also explained the possible mechanisms for both solvatochromism and the detection of Fe(III) through TCFH-Fe(III) complex formation. The binding constant of the generated TCFH-Fe(III) complex was explored. Computational modelling was conducted to explain the deprotonation-triggered changes that occur in the photophysical properties of TCFH dyes.

Plasmid-Mediated Biodegradation of Chlorpyrifos and Analysis of Its Metabolic By-Products.

Organophosphate pesticide persistence is an emerging menace to the environment and despite this fact, its use has been enhanced due to its high efficiency. Bioremediation using microorganisms would be the only means by which these hazardous compounds could be wiped out without disturbing the environmental harmony. The current work studied the molecular mechanism of degradation of Chlorpyrifos (CP) by a bacterial consortium C5 comprising of three soil isolates Staphylococcus warneri (CPI 2), Pseudomonas putida (CPI 9) and Stenotrophomonas maltophilia (CPI 15), which unveiled that the property is plasmid borne. All the isolates were found to possess a 4 kb plasmid which could be cured only by using sodium azide. The Escherichia coli JM109 cells when transformed individually with the plasmid of the isolates showed CP degradation in mineral salts medium (MSM) that contained CP as the sole carbon source. The degradative enzyme organophosphorus hydrolase (~ 60 KDa) of the isolates was extracted and purified to 31.85, 26 and 37.74 fold, respectively. The possible metabolic by-products of CP degradation by the consortium C5, were also analysed. The LC-Q-Tof MS analysis revealed the presence of the major metabolite 3, 5, 6 -trichloropyridine (TCP) with the formation of chlorpyrifos oxon as the intermediate. The isolates also showed trichloropyridine degradation (> 80%) individually in MSM-TCP medium proving its efficiency to remediate both CP and TCP.

Occult Patient Intervention Leading to Misleading Histopathology.

Patients with skin conditions may apply or consume a wide variety of "remedies" with a similarly wide range of effects that may alter the clinical and/or dermatologic presentations of the lesion. Dermatologists or other clinicians should probe for this and carefully document such treatment, as well as any treatment administered by a health care professional or any other person. The dermatopathologist, however, cannot assume that this has been done or done successfully, and therefore must be on constant alert to recognize the effects of such "remedies."

Long-term memory of relative reward values.

Long-term memory can be adaptive as it allows animals to retain information that is crucial for survival, such as the appearance and location of key resources. This is generally examined by comparing choices of stimuli that have value to the animal with those that do not; however, in nature choices are rarely so clear cut. Animals are able to assess the relative value of a resource via direct comparison, but it remains unclear whether they are able to retain this information for a biologically meaningful amount of time. To test this, captive red-footed tortoises (Chelonoidis carbonaria) were first trained to associate visual cues with specific qualities and quantities of food, and their preferences for the different reward values determined. They were then retested after an interval of 18 months. We found that the tortoises were able to retain the information they had learned about the cues as indicators of relative reward values over this interval, demonstrating a memory for the relative quantity and quality of food over an extended period of time. This is likely to impact directly on an animal's foraging decisions, such as the exploitation of seasonally varying resources, with obvious fitness implications for the individual; however, the implications may also extend to the ecological interactions in which the animal is involved, affecting processes such as herbivory and seed dispersal.

A quantitative readability analysis of patient education resources from gastroenterology society websites.

BACKGROUND AND AIMS: The lay public frequently access and rely on online information as a source of their medical knowledge. Many medical societies are unaware of national patient education material guidelines and subsequently fail to meet them. The goal of the present study was to evaluate the readability of patient education materials within the medical field of gastroenterology. METHODS: Two hundred fourteen articles pertaining to patient education materials were evaluated with ten well-established readability scales. The articles were available on the websites for the American College of Gastroenterology (ACG), the American Gastroenterological Association (AGA), the American Society of Gastrointestinal Endoscopy (ASGE), the British Society of Gastroenterology (BSG), and the NIH section National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). One-way analysis of variance (ANOVA) and Tukey's honest significant difference (HSD) post hoc analysis were conducted to determine any differences in level of readability between websites. RESULTS: The 214 articles were written at an 11.8 ± 2.1 grade level with a range of 8.0 to 16.0 grade level. A one-way ANOVA and Tukey's HSD post hoc analysis determined the ACG was written at a significantly (p < 0.05) more difficult level when compared to the AGA, the BSG, and the NIDDK websites. No differences were noted when comparing the ASGE website. CONCLUSIONS: None of the patient education materials were written at a level that met national guidelines. If the materials are redrafted, the general American public will likely have a greater understanding of the gastroenterology content.

Targeting Small Bowel Receptors to Treat Constipation and Diarrhea.

BACKGROUND: The options for the treatment of diarrhea and constipation are evolving as emerging therapies target small bowel receptors. The goal of this review is to discuss small bowel receptors involved in intestinal absorption, secretion, and motility. The review highlights therapies already approved or currently being studied for the modulation of these receptors. METHODS: The articles cited in this review focus on the molecular level of pathways involved in diarrhea and constipation, and highlight the respective pharmacotherapies. RESULTS: The majority of the studies in the current literature investigate the effects of both the small and large intestine receptors on diarrhea and constipation. There are fewer studies that isolate the effects of these receptors solely on the small bowel, and focusing more on the receptors found distinctly in the small intestine may be an area of interest for future studies as this can inspire more targeted therapies.

Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-ß-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-ß signaling may present a potentially effective means for promoting scarless wound healing.

Animal welfare: a social networks perspective.

Social network theory provides a useful tool to study complex social relationships in animals. The possibility to look beyond dyadic interactions by considering whole networks of social relationships allows researchers the opportunity to study social groups in more natural ways. As such, network-based analyses provide an informative way to investigate the factors influencing the social environment of group-living animals, and so has direct application to animal welfare. For example, animal groups in captivity are frequently disrupted by separations, reintroductions and/or mixing with unfamiliar individuals and this can lead to social stress and associated aggression. Social network analysis ofanimal groups can help identify the underlying causes of these socially-derived animal welfare concerns. In this review we discuss how this approach can be applied, and how it could be used to identify potential interventions and solutions in the area of animal welfare.

Colorectal cancer screening patient education materials-how effective is online health information?

PURPOSE: Patients screened for colorectal cancer (CRC) frequently turn to the Internet to improve their understanding of tests used for detection, including colonoscopy, flexible sigmoidoscopy, fecal occult blood test (FOBT), and CT colonography. It was of interest to determine the quality and readability levels of online health information. METHODS: The screening tools were googled, and the top 20 results of each test were analyzed for readability, accessibility, usability, and reliability. The 80 articles excluded scientific literature and blogs. We used ten validated readability scales to measure grade levels, and one-way ANOVA and Tukey's honestly statistical different (HSD) post hoc analyses to determine any statistically significant differences among the four diagnostic tests. The LIDA tool assessed overall quality by measuring accessibility, usability, and reliability. RESULTS: The 80 articles were written at an 11.7 grade level, with CT colonography articles written at significantly higher levels than FOBT articles, F(3, 75) = 3.07, p = 0.033. LIDA showed moderate percentages in accessibility (83.9 %), usability (73.0 %), and reliability (75.9 %). CONCLUSIONS: Online health information about CRC screening tools are written at higher levels than the National Institute of Health (NIH) and American Medical Association (AMA) recommended third to seventh grade levels. More patients could benefit from this modality of information if it were written at a level and quality that would better facilitate understanding.

A gender-based comparison of promotion and research productivity in academic dermatology.

PURPOSE: Gender disparities within academic promotion have been reported in several medical specialties. Female representationin association with research productivity has not been reported among academic dermatologists. As research productivity is a heavily weighted factor in determining promotion, we sought to determine whether gender disparities in academic rank and scholarly impact, measured by the h-index, exist in academic dermatology. METHODS: In 2015, the authors determined gender and academic rank using academic dermatology department websites. H- index and publication range were determined using the Scopus database. Rank, h-index, and publication range were compared between male and female academic dermatologists. RESULTS: The h-index of academic dermatologists increased with successive academic rank from Assistant Professor through Professor (p<0.001), although no significant difference existed between Chairs and Professors. Publication range also increased with each successive rank from Assistant Professor through Professor (p<0.001), with no statistical significant difference between publication range of Chairs and Professors. Overall, men had higher h-indices than female colleagues (p<0.001). This difference was maintained when controlling for academic rank among Assistant Professors, Professors, and Chairs and when controlling for publication range in years. CONCLUSION: Women in academic dermatology are underrepresented among senior academic ranks. The difference in scholarly productivity between male and female academic dermatologists may contribute to this disparity. Recommendation for earlyinvolvement in research activities may help minimize this gap.

The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies.

Broadly neutralizing HIV antibodies (bnAbs) are typically highly somatically mutated, raising doubts as to whether they can be elicited by vaccination. We used 454 sequencing and designed a novel phylogenetic method to model lineage evolution of the bnAbs PGT121-134 and found a positive correlation between the level of somatic hypermutation (SHM) and the development of neutralization breadth and potency. Strikingly, putative intermediates were characterized that show approximately half the mutation level of PGT121-134 but were still capable of neutralizing roughly 40-80% of PGT121-134 sensitive viruses in a 74-virus panel at median titers between 15- and 3-fold higher than PGT121-134. Such antibodies with lower levels of SHM may be more amenable to elicitation through vaccination while still providing noteworthy coverage. Binding characterization indicated a preference of inferred intermediates for native Env binding over monomeric gp120, suggesting that the PGT121-134 lineage may have been selected for binding to native Env at some point during maturation. Analysis of glycan-dependent neutralization for inferred intermediates identified additional adjacent glycans that comprise the epitope and suggests changes in glycan dependency or recognition over the course of affinity maturation for this lineage. Finally, patterns of neutralization of inferred bnAb intermediates suggest hypotheses as to how SHM may lead to potent and broad HIV neutralization and provide important clues for immunogen design.

A critical review of the readability of online patient education resources from RadiologyInfo.Org.

OBJECTIVE: Health consumers and their families rely on the Internet as a source of authoritative information regarding the procedures used to reach a diagnosis, effect treatment, and influence prognosis. In radiology, online materials can be a means by which to offer patients comprehensible explanations of the capabilities, the risks and rewards, and the techniques under our purview. Consequently, estimations of health literacy should take into account the reading level of the average American when composing and transmitting such information to the lay public without the mediation of a referring physician. MATERIALS AND METHODS: In December 2012, patient education reports from the files of RadiologyInfo.org, a jointly sponsored website of the American College of Radiology and the Radiological Society of North America, were downloaded to assess their textual sophistication. All 138 patient education articles including the glossary were analyzed for their respective level of "readability" using the following 10 evaluative scales: Flesch Reading Ease, Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook Grading, Coleman-Liau Index, Gunning Fog Index, New Dale-Chall scale, FORCAST, Fry graph, Raygor Readability Estimate, and New Fog Count. RESULTS: The 138 online patient education articles were written, on average, between the 10th and 14th grade levels, which exceeds both the American Medical Association and the National Institutes of Health recommendations that patient education resources be comprehensible to those who read no higher than the seventh grade level. CONCLUSION: Patients may accrue a greater benefit from written articles available on RadiologyInfo.org if the texts were revised to be in compliance with the National Institutes of Health and American Medical Association grade level recommendations. This could lead to a broadened appreciation of the capabilities of radiology's role in general and enhanced understanding of imaging techniques and their application to clinical practice.

Lanthionine ketimine ethyl ester partially rescues neurodevelopmental defects in unc-33 (DPYSL2/CRMP2) mutants.

Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts with collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), a brain-enriched protein that was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay and biological action of LK and UNC-33, we began examining the nervous system of Caenorhabditis elegans nematodes in which both LK concentrations and UNC-33 protein were manipulated. To this end, a cell-permeable LK-ester (LKE) was administered to developing C. elegans engineered to express yellow fluorescent protein (YFP) in cholinergic neurons (strain RM3128) or green fluorescent protein (GFP) in GABAergic neurons (strain CZ1200), and neural morphology was assessed. Fluorescent imaging analyses show that LKE exposure to wild-type animals induced neural commissure outgrowth, crossing over, and bundling in both neurites from GABAergic and cholinergic motor neurons. Additionally, when unc-33(e204) hypomorph mutant nematodes (D389N substitution mutants) were exposed to LKE, both the neuroanatomical defects of incomplete dorsoventral neural commissures and the ventral nerve cord gaps were partially rescued. In contrast, LKE did not rescue ventral nerve cord gaps found in unc-33(mn407) null mutant. Together these data suggest possible functions for LK as a regulator of neuritic elongation, corroborate roles for UNC-33/CRMP2 in the mechanism of LKE activity, and suggest the potential of LKE as a therapeutic molecule for neurological diseases involving CRMP2 dysfunction.