Reduced expression of annexin A2 is associated with impaired cell surface fibrinolysis and venous thromboembolism.

Reduced plasma fibrinolysis has been identified as a potential risk factor for venous thromboembolism (VTE), but the role of cell surface fibrinolysis in VTE is unknown. The annexin A2/S100A10 complex serves as a coreceptor for plasminogen and tissue plasminogen activator (tPA), augmenting plasmin generation by 60-fold on the endothelial cell surface. Several studies in both mice and humans support the concept that A2 regulates fibrin homeostasis and intravascular thrombosis in vivo. Here, we examined A2 protein expression and function in 115 adult subjects with VTE and 87 healthy controls. Using peripheral blood mononuclear cells as a surrogate for endothelial cells, we found a 41% mean decrease in cell surface tPA-dependent fibrinolytic activity in subjects who had a positive personal and family history of VTE but tested negative for known inherited thrombophilias (ITs). A2 protein was reduced on average by 70% and messenger RNA levels by 30%, but neither decrease correlated with anticoagulant therapy. Neither cell A2 protein nor cell surface plasmin generation correlated with plasma-based clot lysis times, suggesting that the plasma and cell surface fibrinolytic systems operate independently of one another. These data suggest that reduced expression of annexin A2 protein is associated with cell surface hypofibrinolysis and may represent a novel risk factor for IT.

The economic costs of a multisectoral nutrition programme implemented through a credit platform in Bangladesh.

Bangladesh struggles with undernutrition in women and young children. Nutrition-sensitive agriculture programmes can help address rural undernutrition. However, questions remain on the costs of multisectoral programmes. This study estimates the economic costs of the Targeting and Re-aligning Agriculture to Improve Nutrition (TRAIN) programme, which integrated nutrition behaviour change and agricultural extension with a credit platform to support women's income generation. We used the Strengthening Economic Evaluation for Multisectoral Strategies for Nutrition (SEEMS-Nutrition) approach. The approach aligns costs with a multisectoral nutrition typology, identifying inputs and costs along programme impact pathways. We measure and allocate costs for activities and inputs, combining expenditures and micro-costing. Quantitative and qualitative data were collected retrospectively from implementers and beneficiaries. Expenditure data and economic costs were combined to calculate incremental economic costs. The intervention was designed around a randomised control trial. Incremental costs are presented by treatment arm. The total incremental cost was $795,040.34 for a 3.5-year period. The annual incremental costs per household were US$65.37 (Arm 2), USD$114.15 (Arm 3) and $157.11 (Arm 4). Total costs were led by nutrition counselling (37%), agriculture extension (12%), supervision (12%), training (12%), monitoring and evaluation (9%) and community events (5%). Total input costs were led by personnel (68%), travel (12%) and supplies (7%). This study presents the total incremental costs of an agriculture-nutrition intervention implemented through a microcredit platform. Costs per household compare favourably with similar interventions. Our results illustrate the value of a standardised costing approach for comparison with other multisectoral nutrition interventions.

An impact of content delivery, equity, support and self-efficacy on student's learning during the COVID-19.

Due to the outbreak of Covid-19, the colleges and universities across the world have shifted to online classes in place of face-to-face classes. In the wake of this outbreak, the present study focuses on analyzing the impact of sudden shift to online classes, on the undergraduate and postgraduate student's overall learning. The PLS-SEM results concluded that the content delivery has been the most significant construct to impact both self-efficacy and overall learning. The self-efficacy partially mediates the support and equity relationship with the overall learning. The student with greater self-efficacy will have better overall learning from this e-synchronous teaching methodology. However, content delivery has a stronger role in impacting the overall learning even if there is absence of self-efficacy, thus concluding no mediation.

Social assistance programme impacts on women's and children's diets and nutritional status.

Investments in social assistance programmes (SAPs) have accelerated alongside interest in using SAPs to improve health and nutrition outcomes. However, evidence of how design features within and across programme types influence the effectiveness of SAPs for improving diet and nutrition outcomes among women and children is limited. To address this, we reviewed evaluations of cash, in-kind and voucher programmes conducted between 2010 and 2020 among women and children, and examined associations between design features (targeting, including household and individual transfers, fortified foods and behaviour change communication) and positive impacts on diet (diet diversity, micronutrient intake) and nutrition (anthropometric indicators, haemoglobin, anaemia) outcomes. Our review has several key findings. First, SAPs improve dietary diversity and intake of micronutrient-rich foods among women and children, as well as improve several nutrition outcomes. Second, SAPs were more likely to impact diet and nutrition outcomes among women compared with children (23/45 [51%] vs. 52/144 [36%] of outcomes measured). Third, in-kind (all but one of which included fortified foods) compared with cash transfer programmes were more likely to significantly increase women's body mass index and children's weight-for-height/length Z-score, and both women's and children's haemoglobin and anaemia. However, there is limited evidence on the effectiveness of SAPs for improving micronutrient status and preventing increased prevalence of overweight and obesity for all populations and for improving diet and nutrition outcomes among men, adolescents and the elderly. Further research in these areas is urgently needed to optimize impact of SAPs on diet and nutrition outcomes as countries increase investments in SAPs.

Polycyclic Arene-Fused Selenophenes via Site Selective Selenocyclization of Arylethynyl Substituted Polycyclic Arenes.

Arene-fused selenophenes were synthesized by a redox neutral process from arylethynyl substituted polycyclic arenes using selenium powder in refluxing N-methyl-2-pyrrolidone (NMP) with the assistance of the residual water in NMP as a catalytic proton source. The site-selective nature of this selenocyclization produces trans-alkenes as a competitive product, which is dependent on the π-electron donation ability of polycyclic arenes and the kind of arylethynyl group attached to it. DFT calculations were performed to understand the site selectivity in the selenophene formation reaction. The HOMO coefficient on the carbon adjacent to carbon having arylalkyne substituent of the polycyclic arene correlates with the selenocyclization tendency of the substrate. The wavelength of absorption and emission and quantum yield of emission increase with increasing the number of fused benzene rings in the polycyclic unit (from naphthalene to pyrene).

The power of the collective empowers women: Evidence from self-help groups in India.

Women's groups are important rural social and financial institutions in South Asia. In India, a large majority of women's groups programs are implemented through self-help groups (SHGs). Originally designed as savings and credit groups, the role of SHGs has expanded to include creating health and nutrition awareness, improving governance, and addressing social issues related to gender- and caste-based discrimination. This paper uses panel data from 1470 rural Indian women from five states to study the impact of SHG membership on women's empowerment in agriculture, using the project-level Women's Empowerment in Agriculture Index (pro-WEAI) and the abbreviated Women's Empowerment in Agriculture Index (A-WEAI). Because SHG membership was not randomized and women who self-select to be SHG members may be systematically different from non-members, we employ nearest neighbor matching methods to attribute the impact of SHG membership on women's empowerment in agriculture and intrahousehold inequality. Our findings suggest that SHG membership has a significant positive impact on aggregate measures of women's empowerment and reduces the gap between men's and women's empowerment scores. This improvement in aggregate empowerment is driven by improvements in women's scores, not a deterioration in men's. Greater control over income, greater decisionmaking over credit, and (somewhat mechanistically, given the treatment) greater and more active involvement in groups within the community lead to improvements in women's scores. However, impacts on other areas of empowerment are limited. The insignificant impacts on attitudes towards domestic violence and respect within the household suggest that women's groups alone may be insufficient to change deep-seated gender norms that disempower women. Our results have implications for the design and scale-up of women's group-based programs in South Asia, including the possibility that involving men is needed to change gender norms.

Working in lockdown: the relationship between COVID-19 induced work stressors, job performance, distress, and life satisfaction.

BACKGROUND & AIM: In the wake of COVID-19, organizations all over India have closed their premises and shifted to work from home policy to curb the further spread of the virus. This has led to increased stress and anxiety among employees, which explicably affects their satisfaction with life. Thus, the present study analyses the effect of COVID-19 induced stressors (role overload, lifestyle choices, family distraction, and occupational discomfort) on employees' distress levels and job performance. Subsequently, the impact of such distress and job performance on the employees' life satisfaction is analyzed during the lockdown period. METHODOLOGY: Data was collected from 433 working professionals of private and public organizations in the Delhi and NCR region of India during India's third and fourth phase of lockdown via a survey, which was distributed online. Partial least squares structural equation modelling was applied first to establish the validity of this study's model (measurement model validity) and subsequently test the hypothesized relationships in the model (structural model). RESULTS: The COVID-19 induced stressors, i.e., role overload, lifestyle choices, and occupational discomfort, were significant predictors of distress during the lockdown. It has been found that role overload and change in lifestyle choice did not significantly affect job performance. Family distraction, occupational discomfort, and distress were significant in impacting job performance, with distress being the most significant one. During the COVID-19 pandemic, life satisfaction has reduced due to a significant increase in distress levels and lowered job performances. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-01567-0.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses.

BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow-up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP-SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP-SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP-SMX had a hypersensitivity reaction. CONCLUSIONS: As compared with incision and drainage alone, clindamycin or TMP-SMX in conjunction with incision and drainage improves short-term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side-effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028 .).

The Effect of Base and Nucleophile on the Nucleophilic Substitution of Methoxytropone Derivatives: An Easy Access to 4- and 5-Substituted Multifunctional Azulenes.

The nucleophilic substitution on 3-substituted 2-methoxytropones to form azulenes is dependent on the nucleophile and base employed. With bulkier nucleophiles (ethyl/methyl cyanoacetate), the reaction proceeds with the abnormal nucleophilic substitution irrespective of the base and with smaller nucleophiles (malononitrile), the reaction follows base-dependent normal and abnormal nucleophilic substitution. Thus, the methodologies are developed to selectively obtain 4- and 5-substituted azulenes based on the nature of bases and nucleophiles employed.

Randomized controlled trials of multi-sectoral programs: Lessons from development research.

Development is a multi-faceted process; achieving development goals thus requires a multi-sectoral approach. For over two decades, our research group of economists and nutritionists has designed and implemented randomized trials to assess the effectiveness of multisectoral programs in improving nutrition, food security, and other measures of well-being, largely at the request of developing country governments, development partners, and non-governmental organizations. Our approach addresses three perceived pitfalls of RCTs: the "black box" nature of RCTs, limited external validity, and challenges in translation of results to impacts at scale. We address these concerns by identifying and assessing programmatic pathways to impact with quantitative and qualitative methods; studying similar programs implemented by different organizations across various settings; and working closely with implementing partners in the design, research, and dissemination processes to inform adaptation and scale-up of programs and policies.

Bargaining power, decision making, and biofortification: The role of gender in adoption of orange sweet potato in Uganda.

We examine the role of gender dimensions of intrahousehold bargaining power and decision making in the adoption and diffusion of orange sweet potato (OSP), a biofortified crop being promoted to increase dietary intakes of vitamin A in Uganda. We use patterns of ownership and control of land and other assets by married men and women to create gender-disaggregated indicators of bargaining power, allowing for joint and sole ownership and control of land and assets. Using data from an experimental evaluation of a project promoting OSP adoption, we find that the probability of adopting OSP is not affected by the exclusive or joint control of assets by women at the household level. However, within households, parcels of land under joint control, in which the woman has primary control over decision making, are significantly more likely to contain OSP. Women who control a higher share of household nonland resources are more likely to share OPS vines, showing that women use greater bargaining power to facilitate diffusion of this health-promoting technology. We do not find any impact of women's bargaining power on children's dietary intakes of Vitamin A, possibly because husbands and wives have the same preferences regarding their children's nutritional status. These results contribute to reshaping our understanding of household decision making to inform the design and implementation of agriculture-nutrition interventions.

Abnormal Nucleophilic Substitution on Methoxytropone Derivatives: Steric Strategy to Synthesize 5-Substituted Azulenes.

Azulene is a non-alternant non-benzenoid aromatic system, and in turn, it possesses unusual photophysical properties. Azulene-based conjugated systems have received increasing interest in recent years as optoelectronic materials. Despite the routes available for the preparation of substituted azulene derivatives, there remain few methods that allow regioselective substitution on the seven-membered ring of azulenes due to the subtle reactivity difference among the various positions. This report explores the reactivity of substituted tropolones as the azulene precursors and also provides a new method to create 5-substituted azulenes. The reaction of cyanoacetate enolate with unsubstituted 2-methoxytropone affords azulene through the attack of the nucleophile on the C-2 center (normal pathway). We have observed that 3-substituted 2-methoxytropones undergo steric-guided nucleophilic addition at the C-7 center (abnormal pathway) to afford 5-substituted azulene derivatives. Based on this observation and DFT calculation, a new synthetic strategy is devised for the regioselective synthesis of 5-substituted multifunctional azulenes, which cannot be accessed by any other method.

Iatrogenic CNS demyelination in the era of modern biologics.

The number of reported cases of iatrogenic demyelination of the central nervous system (CNS) is on the rise. This is, in part, related to the recent expansion in the use of biologics. Review of literature from the past decade suggests that in addition to vaccines, tumor necrosis factor (TNF)-alpha inhibitors and checkpoint inhibitors are the most frequently cited inducers of central inflammation. About one-third of demyelinating cases in the setting of TNF-alpha inhibitors evolve into full-blown multiple sclerosis. In addition to demyelination, checkpoint inhibitors may also cause accelerated paraneoplastic encephalitis and other antibody-mediated conditions. Luckily, the overall prognosis of iatrogenic central inflammation is favorable, with most cases having partial or complete response to steroids and discontinuation of the offending agent. Long-term monitoring and initiation of maintenance immune-modulating therapy may be necessary in some patients. In this article, we provide an updated review of biologic-induced inflammation of the CNS.

Managing the need to tell: Triggers and strategic disclosure of thalassemia major in Singapore.

This study explored patients' experiences and perceptions of living with thalassemia (an inherited hematologic disorder), perceptions of social stigma, and impact on disclosure decision-making. Semistructured, in-person interviews were conducted in Singapore with 30 individuals: 16 thalassemia major patients and 14 parents of children with thalassemia. Findings were indicative of felt or enacted stigma that may have influenced disclosure decisions. Although affected individuals commonly disclosed their thalassemia diagnosis to family members, they either downplayed the condition with or avoided disclosure to unrelated individuals. Disclosure outside the family occurred only in response to triggers, such as questions about absences due to medical care. Health professionals should provide anticipatory guidance about disclosure strategies when managing individuals with thalassemia.

Ethnicity and health outcomes among people with epilepsy participating in an epilepsy self-management RCT.

People with epilepsy (PWE) may experience negative health events (NHEs) such as seizures, emergency room visits, and hospitalizations, with ethnic and racial minorities disproportionately affected. Epilepsy self-management may reduce NHEs; however, few reports examine self-management outcomes in racial minorities. Using data from a longitudinal 6-month randomized controlled trial (RCT) of 120 PWE, this analysis compared African-American and Whites at baseline, 10 weeks and 24 weeks after receiving the "Self-management for people with epilepsy (SMART) and a history of NHEs" self-management program. The primary RCT outcome was number of NHEs. At baseline, compared to Whites, African-Americans had less education (p = 0.02) and greater depressive severity (p = 0.04). Both African-American and Whites generally improved with SMART, and there were no racial differences in NHE counts or other outcomes' responses. Given known racial disparities in epilepsy care, it may be particularly important to reach out to minority PWE with self-management programs.

Depressive Symptom Severity in Individuals With Epilepsy and Recent Health Complications.

Identifying relationships between depression severity and clinical factors may help with appropriate recognition and management of neuropsychiatric conditions in persons with epilepsy (PWE). Demographic characteristics, epilepsy variables, and medical and psychiatric comorbidities were examined from a baseline randomized controlled trial sample of 120 PWE. Among demographic characteristics, only inability to work was significantly associated with depression severity (p = 0.05). Higher 30-day seizure frequency (p < 0.01) and lower quality of life (p < 0.0001) were associated with greater depression severity. Comorbid bipolar disorder (p = 0.02), panic disorder (p < 0.01), and obsessive-compulsive disorder (p < 0.01) were correlated with worse depression severity. The literature supports our findings of correlations between worse depression, seizure frequency, and lower quality of life. Less well studied is our finding of greater depression severity and selected psychiatric comorbidities in PWE.

Social networks, mobility, and political participation: The potential for women's self-help groups to improve access and use of public entitlement schemes in India.

Women's self-help groups (SHGs) have increasingly been used as a vehicle for social, political, and economic empowerment as well as a platform for service delivery. Although a growing body of literature shows evidence of positive impacts of SHGs on various measures of empowerment, our understanding of ways in which SHGs improve awareness and use of public services is limited. To fill this knowledge gap, this paper first examines how SHG membership is associated with political participation, awareness, and use of government entitlement schemes. It further examines the effect of SHG membership on various measures of social networks and mobility. Using data collected in 2015 across five Indian states and matching methods to correct for endogeneity of SHG membership, we find that SHG members are more politically engaged. We also find that SHG members are not only more likely to know of certain public entitlements than non-members, they are significantly more likely to avail of a greater number of public entitlement schemes. Additionally, SHG members have wider social networks and greater mobility as compared to non-members. Our results suggest that SHGs have the potential to increase their members' ability to hold public entities accountable and demand what is rightfully theirs. An important insight, however, is that the SHGs themselves cannot be expected to increase knowledge of public entitlement schemes in absence of a deliberate effort to do so by an external agency.

Ex ante and ex post effects of hybrid index insurance in Bangladesh.

This study assesses both the demand for and effectiveness of an index insurance product designed to help smallholder farmers in Bangladesh manage crop production risk during the monsoon season. Villages were randomized into either an insurance treatment or a comparison group, and discounts and rebates were randomly allocated across treatment villages to encourage insurance take-up and to allow for the estimation of the price-elasticity of insurance demand. Among those offered insurance, we find demand to be fairly price elastic, with discounts significantly more successful in stimulating demand than rebates. Purchasing insurance yields both ex ante risk management effects as well as ex post income effects on agricultural production practices. The risk management effects lead to an expansion of cultivated area with concomitant increases in agricultural input expenditures during the monsoon season. The income effects lead to more intensive rice production during the subsequent dry season, with more intensive use of both irrigation and fertilizers, resulting in higher yields and higher total rice production.

Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans.

Staphylococcus aureus is both a commensal and a pathogen, and USA300, a strain that is usually methicillin-resistant but can sometimes be methicillin-susceptible, has been causing skin and soft tissue infections (SSTIs) in epidemic proportions among otherwise healthy individuals. Although many people are colonized with S. aureus strains, including some with USA300, few of these colonized individuals develop SSTIs. This prompts the hypothesis that infections may develop in individuals with somewhat reduced innate and/or adaptive immune responses to S. aureus, either because prior S. aureus colonization has dampened such responses selectively, or because of more globally reduced immune reactivity. In this study, we analyzed the S. aureus colonization status and PBMC responses to innate and adaptive stimuli in 72 patients with SSTIs and 143 uninfected demographically matched controls. Contrary to the hypothesis formulated, PBMCs from infected patients obtained at the time of infection displayed enhanced innate cytokine production upon restimulation compared with PBMCs from controls, a difference that disappeared after infection resolution. Notably, PBMCs from patients infected with a documented USA300 SSTI displayed greater innate cytokine production than did those from patients infected with documented non-USA300 genotypes. Moreover, colonization with USA300 in infected patients, regardless of their infecting strain, correlated with increased production of IL-10, IL-17A, and IL-22 compared with patients colonized with non-USA300 subtypes. Thus, our results demonstrate that infected patients associated with USA300 either as an infecting strain, or as a colonizing strain, have systemic immune responses of greater magnitude than do those associated with other S. aureus subtypes.

Clinical correlates of negative health events in a research sample with epilepsy.

AIMS: In spite of advances in care, people with epilepsy experience negative health events (NHEs), such as seizures, emergency department (ED) visits, and hospitalizations. Being able to identify characteristics that are associated with NHE risk can help inform care approaches that reduce complications and burden. This analysis using baseline data from a larger randomized epilepsy self-management clinical trial assessed the relationship between demographic and clinical variables vs. seizure-related complications among people with epilepsy. METHODS: Data were derived from a baseline sample of a larger prospective study of 120 individuals with epilepsy who experienced an NHE within the last 6months. Demographic characteristics, depression assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the Montgomery-Asberg Depression rating scale (MADRS), quality of life assessed with the 10-item Quality of Life in Epilepsy Inventory (QOLIE-10), self-efficacy assessed the Epilepsy Self-Efficacy Scale (ESES), social support assessed with the Multidimensional Scale of Perceived Social Support (MSPSS), self-management assessed with the Epilepsy Self-Management Scale (ESMS), and stigma assessed with the Epilepsy Stigma Scale (ESS) were all examined in association with past 6-month NHE frequency and 30-day seizure frequency. RESULTS: Except for lower levels of education and lower levels of income being associated with higher 30-day and 6-month seizure frequency, demographic variables were generally not significantly associated with NHEs. Higher 30-day seizure frequency was associated with greater depression severity on PHQ-9 (p<0.01) and MADRS (p<0.01). Higher 6-month seizure frequency was also associated with greater depression severity on PHQ-9 (p<.001) and MADRS (p=0.03). Both 30-day and 6-month seizure frequency were significantly negatively associated with QOLIE-10 (p<0.001). Both 30day (p=0.01) and 6-month (p=0.03) seizure frequency were associated with worse stigma on ESS. Total NHE count was associated with more severe depression on PHQ-9 (p=0.02), and MADRS (p=0.04), worse quality of life on QOLIE-10 (p<0.01), and more stigma on ESS (p=0.03). CONCLUSIONS: Consistent with previous literature, more frequent seizures were associated with worse depression severity and quality of life. A finding that is less established is that higher seizure frequency is also associated with worse epilepsy-related stigma. Epilepsy self-management approaches need to address depression and stigma as well as seizure control.