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BACKGROUND: Women in South Asia often return to their natal home during pregnancy, for childbirth, and stay through the postpartum period-potentially impacting access to health care and health outcomes in this important period. However, this phenomenon is understudied (and not even named) in the demographic or health literature, nor do we know how it impacts health. OBJECTIVE: The aim of this study is to measure the magnitude, timing, duration, risk factors and impact on care of this phenomenon, which we name Temporary Childbirth Migration. METHODS: Using data from 9,033 pregnant and postpartum women collected in 2019 in two large states of India (Madhya Pradesh and Bihar) we achieve these aims using descriptive statistics and logistic regression models, combined with qualitative data from community health workers about this practice. RESULTS: We find that about one third of women return to their natal home at some point in pregnancy or postpartum, mostly clustered close to the time of delivery. Younger, primiparous, and non-Hindu women were more likely to return to their natal home. Women reported that they went to their natal home because they believed that they would receive better care; this was born out by our analysis in Bihar, but not Madhya Pradesh, for prenatal care. CONCLUSIONS: Temporary childbirth migration is common, and, contrary to expectations, did not lead to disruptions in care, but rather led to more access to care. CONTRIBUTION: We describe a hitherto un-named, underexplored yet common phenomenon that has implications for health care use and potentially health outcomes.

Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity.

IntroductionIn India, the HIV epidemic is concentrated among Key Populations (KPs), such as men who have sex with men (MSM), who bear a disproportionate burden of HIV disease. Conventional targeted interventions (TI) mitigate HIV transmission among MSM by focusing on physical hotspots. As increasingly, there is a shift within India's MSM community to connect with sex partners online, novel approaches are needed to map virtual platforms where sexual networks are formed. The objective of this study was to estimate the number of MSM in Delhi using virtual platforms to connect for sex and to describe patterns of their use.MethodsThe study was conducted in the state of Delhi among MSM over 18 years of age who used virtual platforms to look for sexual partners. Virtual platforms were identified through community consultations. Size estimation was carried out by enumerating the number of online users, accounting for duplication across sites and time and based on interviews with 565 MSM.Results28,058 MSM (95% CI: range 26,455-29,817) use virtual sites to find sexual partners. We listed 14 MSM specific virtual sites, 14 general virtual sites, 19 social networking pages and 112 messenger groups, all used by MSM. Five virtual sites met feasibility criteria to be included in the virtual mapping. Of the MSM on these sites, 81% used them at night and 94% used them on Sundays, making these the peak time and day of use. Only 16% of users were aware of organizations providing HIV services and 7% were contacted by peer educators in the preceding three months. Two-fifths (42%) also visited a physical location to connect with sexual partners in the month prior to the study.DiscussionTI programs that focus on physical hotspots do not reach the majority of MSM who use virtual sites. MSM active on virtual sites have a low awareness of HIV services. Virtual mapping and programmatic interventions to include them must be incorporated into current public health interventions to reach MSM at risk of HIV.

Beedi is the most common smoking form of tobacco used in India. The rolling of beedis is performed primarily by women in settings that lack occupational safeguards. The aims of this protocol are to establish methods for the study of occupational exposures among women beedi workers and their experiences and challenges working with unburnt tobacco. This protocol employs a convergent parallel mixed-methods approach. Qualitatively, we plan to explore the experiences and challenges faced by women beedi workers using photovoice, a community based participatory method. Occupational exposures to pesticides will be assessed through the use of silicone wristbands worn for seven days by workers, and exposure to toxic metals and metalloids will be assessed in dust samples collected in the homes of workers. The outcomes will be analyzed to form policy recommendations to improve the occupational health of women beedi workers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ravi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Women in South Asia often return to their natal home during pregnancy, for childbirth, and stay through the postpartum period-potentially impacting access to health care and health outcomes in this important period. However, this phenomenon is understudied (and not even named) in the demographic or health literature, nor do we know how it impacts health., Objective: The aim of this study is to measure the magnitude, timing, duration, risk factors and impact on care of this phenomenon, which we name Temporary Childbirth Migration., Methods: Using data from 9,033 pregnant and postpartum women collected in 2019 in two large states of India (Madhya Pradesh and Bihar) we achieve these aims using descriptive statistics and logistic regression models, combined with qualitative data from community health workers about this practice., Results: We find that about one third of women return to their natal home at some point in pregnancy or postpartum, mostly clustered close to the time of delivery. Younger, primiparous, and non-Hindu women were more likely to return to their natal home. Women reported that they went to their natal home because they believed that they would receive better care; this was born out by our analysis in Bihar, but not Madhya Pradesh, for prenatal care., Conclusions: Temporary childbirth migration is common, and, contrary to expectations, did not lead to disruptions in care, but rather led to more access to care., Contribution: We describe a hitherto un-named, underexplored yet common phenomenon that has implications for health care use and potentially health outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Diamond-Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Adequate peri-operative care is essential to ensuring a satisfactory outcome in cardiac surgery. In this study, we look at the impact of evidence-based protocols implemented at Stanford Hospital., Methods: This study is a single-center, retrospective analysis. Enhanced recovery after surgery (ERAS) protocols were implemented for CABG/Valve and open Aortic operations on 11/1/2017 and 6/1/2018, respectively. Propensity-score matched analysis was used to compare 30-day mortality and morbidity of patients from the pre- and post-implementation cohorts. Secondary endpoints included the following: total hospital length of stay (LOS), ICU LOS, time until extubation, and time until urinary catheter removal., Results: After the implementation of the ERAS protocols for CABG/Valve operations, the median post-op LOS decreased from 7.0 days to 6.1 days (p<0.001), and median ICU LOS decreased from 69.9 hours to 54.0 (p = 0.098). There was no significant decrease in 30-day mortality (4% to 3.3%, p = 0.47). However, the incidence of post-op ventilator associated pneumonia (VAP) decreased from 5.0% to 2.1% (p = 0.003) and post-op urinary tract infections (UTIs) from 8.3% to 3.6% (p<0.001). Patients who underwent open aortic procedures experienced an improvement in 30-day mortality (7% to 3.5%, p = 0.012), decrease in median ICU LOS (91.7 hours to 69.6 hours, p<0.001), and a decrease in duration of mechanical ventilation (79.3 hours to 46.3 hours, p = 0.003). There was a decrease in post-op LOS, post-op VAP, and post-op UTI, although statistical significance was not attained., Conclusion: At Stanford Hospital, ERAS pathways have led to decreased morbidity and LOS while simultaneously improving mortality amongst our critically ill patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Obafemi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Bangladesh is experiencing a nutrition transition with an increase in the double burden of malnutrition and non-communicable diseases (NCDs). This study sought to: 1) examine trends and differences in underweight, overweight/obesity, hypertension and diabetes by gender, area of residence, and wealth in Bangladesh from 2004 to 2018, 2) assess what factors contributed to changes in these outcomes., Methods: We used data from five rounds of the Bangladesh Demographic and Health Surveys (n = 76,758 women 15-49y and 10,900 men 18-95y in total). We calculated differences, slope index of inequality (SII) and concentration index (CIX) to examine trends over time and differences in outcomes by wealth and residence. We identified determinants and estimated drivers of changes in outcomes using regression-based decomposition., Results: Between 2004 and 2018, underweight prevalence decreased in both women (33% to 12%) and men (26% to 18%), whereas overweight/obesity increased (17% to 49% in women and 21% to 34% in men). Hypertension also increased in both women (31% to 44%) and men (19% to 33%) while diabetes changed marginally (11% to 14%). In all years, underweight was concentrated in poorer and rural households while overweight/obesity, diabetes and hypertension were concentrated in wealthier and urban households. Wealth inequity decreased over time for underweight, changed little for overweight/obesity, and increased for hypertension and diabetes among men. Increases in wealth explained 35% to 50% of the reduction in underweight and 30% to 57% of the increase in overweight/obesity., Conclusion: Our findings imply that double duty actions are required to sustain the decrease in undernutrition and slow the increase in overweight/obesity and NCDs across diverse socioeconomic sections of the population in Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

Background: Modeling studies estimated severe impacts of potential service delivery disruptions due to COVID-19 pandemic on maternal and child nutrition outcomes. Although anecdotal evidence exists on disruptions, little is known about the actual state of service delivery at scale. We studied disruptions and restorations, challenges and adaptations in health and nutrition service delivery by frontline workers (FLWs) in India during COVID-19 in 2020., Methods: We conducted phone surveys with 5500 FLWs (among them 3118 Anganwadi Workers) in seven states between August-October 2020, asking about service delivery during April 2020 (T1) and in August-October (T2), and analyzed changes between T1 and T2. We also analyzed health systems administrative data from 704 districts on disruptions and restoration of services between pre-pandemic (December 2019, T0), T1 and T2., Results: In April 2020 (T1), village centers, fixed day events, child growth monitoring, and immunization were provided by <50% of FLWs in several states. Food supplementation was least disrupted. In T2, center-based services were restored by over a third in most states. Administrative data highlights geographic variability in both disruptions and restorations. Most districts had restored service delivery for pregnant women and children by T2 but had not yet reached T0 levels. Adaptations included home delivery (60 to 96%), coordinating with other FLWs (7 to 49%), and use of phones for counseling (~2 to 65%). Personal fears, long distances, limited personal protective equipment, and antagonistic behavior of beneficiaries were reported challenges., Conclusions: Services to mothers and children were disrupted during stringent lockdown but restored thereafter, albeit not to pre-pandemic levels. Rapid policy guidance and adaptations by FLWs enabled restoration but little remains known about uptake by client populations. As COVID-19 continues to surge in India, focused attention to ensuring essential services is critical to mitigate these major indirect impacts of the pandemic., Competing Interests: The authors have declared that no competing interests exist.

Malnutrition during pregnancy is associated with increased maternal morbidity and mortality and has a long-term negative impact on child growth and development. Antenatal care (ANC) is the formal point of contact for pregnant women to receive preventive health and nutrition services. We assessed the quality of nutrition service delivery during ANC and examined its influencing factors related to the health facility, health care provider (HCP) and client characteristics. We conducted a cross-sectional assessment in 179 facilities, including 1,242 ANC observations and exit interviews of pregnant women from 21 districts in Bangladesh. We considered four essential nutrition services at each ANC contact including maternal weight measurement, anaemia assessment, nutrition counselling and iron-folic acid (IFA) supplement provision. We defined a composite 'quality nutrition service' outcome by counting the number of services (out of four) provided at each ANC from observation data. We explored both the supply-side and the client-level factors of quality nutrition service using multilevel Poisson regression. Overall, only 15% of clients received all four nutrition services. Performance of weight measurement (79%) was higher than IFA provision (56%), anaemia assessment (52%) and nutrition counselling (52%). The multivariable analysis showed that quality nutrition service delivery is positively associated with good logistical readiness of the facilities (aIRR: 1.23, 95% CI: 1.08-1.39), consultation by paramedics (aIRR 1.23, 95% CI: 1.06-1.42) and community health care providers (aIRR 1.32, 95% CI: 1.12-1.57), HCPs' knowledge on maternal nutrition (aIRR 1.04; 95% CI: 1.01-1.08), better HCP-client communication (aIRR 1.14; 95% CI: 1.04-1.26) and use visual aids or ANC card (aIRR 1.18; 95% CI: 1.11-1.27). We found limited associations between HCP training and external supervision with the quality of nutrition services. In conclusion, the quality of nutrition service provision during ANC is suboptimal. Public health nutrition programmers should ensure the facilities' logistical readiness, and revisit and reinforce the content and modality of training and supportive supervision of the HCPs. They should also emphasize positive HCP-client communication and the use of job aids to improve the quality of nutrition service provision during ANC., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Sufia Askari is from the funding agency. She contributed to the study concept but played no role in study design, data collection or data analysis. Her contributions to this manuscript included inputs to the section on interpretation of results and review of manuscript drafts. However, the final decision about the results to include, interpretation and conclusion rested with the lead author and the authors from the evaluation team. All other authors declare that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Rapid urban expansion has important health implications. This study examines trends and inequalities in undernutrition and overnutrition by gender, residence (rural, urban slum, urban non-slum), and wealth among children and adults in India. We used National Family Health Survey data from 2006 and 2016 (n = 311,182 children 0-5y and 972,192 adults 15-54y in total). We calculated differences, slope index of inequality (SII) and concentration index to examine changes over time and inequalities in outcomes by gender, residence, and wealth quintile. Between 2006 and 2016, child stunting prevalence dropped from 48% to 38%, with no gender differences in trends, whereas child overweight/obesity remained at ~7-8%. In both years, stunting prevalence was higher in rural and urban slum households compared to urban non-slum households. Within-residence, wealth inequalities were large for stunting (SII: -33 to -19 percentage points, pp) and declined over time only in urban non-slum households. Among adults, underweight prevalence decreased by ~13 pp but overweight/obesity doubled (10% to 21%) between 2006 and 2016. Rises in overweight/obesity among women were greater in rural and urban slum than urban non-slum households. Within-residence, wealth inequalities were large for both underweight (SII -35 to -12pp) and overweight/obesity (+16 to +29pp) for adults, with the former being more concentrated among poorer households and the latter among wealthier households. In conclusion, India experienced a rapid decline in child and adult undernutrition between 2006 and 2016 across genders and areas of residence. Of great concern, however, is the doubling of adult overweight/obesity in all areas during this period and the rise in wealth inequalities in both rural and urban slum households. With the second largest urban population globally, India needs to aggressively tackle the multiple burdens of malnutrition, especially among rural and urban slum households and develop actions to maintain trends in undernutrition reduction without exacerbating the rapidly rising problems of overweight/obesity., Competing Interests: The authors have declared that no competing interests exist.

Globally, there remain significant knowledge and evidence gaps around how to support Community Health Worker (CHW) programmes to achieve high coverage and quality of interventions. India's Integrated Child Development Services scheme employs the largest CHW cadre in the world-Anganwadi Workers (AWWs). However, factors influencing the performance of these workers remain under researched. Lessons from it have potential to impact on other large scale global CHW programmes. A qualitative study of AWWs in the Indian state of Bihar was conducted to identify key drivers of performance in 2015. In-depth interviews were conducted with 30 AWWs; data was analysed using both inductive and deductive thematic analysis. The study adapted and contextualised existing frameworks on CHW performance, finding that factors affecting performance occur at the individual, community, programme and organisational levels, including factors not previously identified in the literature. Individual factors include initial financial motives and family support; programme factors include beneficiaries' and AWWs' service preferences and work environment; community factors include caste dynamics and community and seasonal migration; and organisational factors include corruption. The initial motives of the worker (the need to retain a job for family financial needs) and community expectations (for product-oriented services) ensure continued efforts even when her motivation is low. The main constraints to performance remain factors outside of her control, including limited availability of programme resources and challenging relationships shaped by caste dynamics, seasonal migration, and corruption. Programme efforts to improve performance (such as incentives, working conditions and supportive management) need to consider these complex, inter-related multiple determinants of performance. Our findings, including new factors, contribute to the global literature on factors affecting the performance of CHWs and have wide application., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Adolescent wellbeing is critical to breaking the intergenerational cycle of poverty and one in five of the world's adolescents live in India. We explored predictors of learning skills and depression in Indian adolescents., Methods: Data on adolescents aged 10-19y (three groups: 5,840 unmarried males, 8,953 unmarried females, 4,933 married females) were available from the state-representative Understanding the Lives of Adolescents and Young Adults survey in Uttar Pradesh and Bihar. Multivariable logistic regression models adjusted for cluster sampling design and state fixed effects were used to examine factors (demographic, health/nutrition, social, and environmental) associated with three outcomes: reading proficiency, math proficiency, and depressive symptoms., Findings: Learning skills were poor (28-61% lacked basic reading and math skills depending on adolescent group and outcome) and depression was common (8-26%). Better learning skills were predicted by greater household wealth (AOR 1.72-2.55 depending on group) and household head education (AOR 1.03-1.07 per year), being in school (AOR 4.19-18.65), parental support (AOR 1.11-1.39), having gender equal attitudes (AOR 1.56-2.67), number of food groups consumed at least weekly (unmarried females: AOR 1.11), and having an improved latrine (AOR 1.33-1.51). Poorer learning skills were predicted by family substance use (AOR 0.68-0.74), underweight (males: AOR 0.74), witnessing parental violence (AOR 0.66-0.78). Depressive symptoms were predicted by witnessing parental violence (AOR 1.51-1.92) and experiencing sexual abuse (AOR 2.30-6.16)., Conclusion: Factors across multiple life dimensions are associated with learning skills and depression in Indian adolescents. Adolescent-focused policies and programs should consider health/nutrition, social, and environmental aspects of life in vulnerable individuals., Competing Interests: The authors have no conflicts of interest. The study sponsor had no role in the study design, data collection, data analysis, data interpretation, report writing, or decision to submit the manuscript for publication.

Objectives: This study used a health belief theory derived framework and structural equation model to examine moderators, mediators, and direct and indirect predictors of childhood vaccination., Methods: A secondary analysis was conducted using data collected from a cross-sectional survey of a random sample of 1599 parents living in urban and rural areas of Mysore district, India. Applying two-stage probability proportionate-to-size sampling, adolescent girls attending 7th through 10th grades in 23 schools were selected to take home a questionnaire to be answered by their parents to primarily assess HPV vaccine intentions. Parents were also asked whether their children had received one dose of Bacillus Calmette-Guérin; three doses of Diphtheria, Pertussis, Tetanus; three doses of oral Polio vaccine; and one dose of Measles vaccine. In addition, parents were asked about their attitudes towards childhood vaccination., Results: Out of the 1599 parents, 52.2% reported that their children had received all the routine vaccines (fully vaccinated); 42.7% reported their children had missed at least one routine vaccine, and 5.2% reported that their children had missed all routine vaccinations. Perceptions about the benefits/facilitators to childhood vaccination significantly predicted the full vaccination rate (standardized regression coefficient (β) = 0.29) directly and mediated the effect of parental education (β = 0.11) and employment (β = -0.06) on the rate of full vaccination. Parental education was significantly associated indirectly with higher rates of full vaccination (β = 0.11). Parental employment was significantly associated indirectly with decreasing rates of full vaccination (β = -0.05). Area of residence moderated the role of religion (β = 0.24) and the 'number of children' in a family (β = 0.33) on parental perceptions about barriers to childhood vaccination. The model to data fit was acceptable (Root Mean Square Error of Approximation = 0.02, 95% CI 0.018 to 0.023; Comparative Fit Index = 0.92; Tucker-Lewis Index = 0.91)., Conclusions: Full vaccination rate was relatively low among children in Mysore, especially among parents who were unsure about the benefits of routine vaccination and those with low educational levels. Interventions increasing awareness of the benefits of childhood vaccination that target rural parents with lower levels of education may help increase the rate of full childhood vaccination in India., Competing Interests: This study was awarded from Merck & Co., Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Common mental disorders (CMD) among mothers cause disability, negatively affect child development, and have high long-term economic costs. Little is known about how factors across multiple life dimensions, modeled together, are differentially related to maternal mental health in high poverty contexts. Further, there is limited evidence on determinants of CMD in areas where self-help groups (SHGs) exist to promote women's wellbeing. Filling this evidence gap is important given the high prevalence of CMD and the rapid expansion of SHGs in rural India. Cross-sectional data were collected from 1644 mother-infant pairs living in disadvantaged rural villages across five Indian states-Jharkhand, Madhya Pradesh, West Bengal, Odisha, and Chhattisgarh-surveyed in the Women Improving Nutrition through Group-based Strategies study. CMD were assessed using the 20-item Self Reporting Questionnaire (SRQ). We examined 31 factors across four life dimensions: work (work type, time spent in labor, domestic and caretaking activities), agency (SHG membership, decision-making, gender attitudes), health/nutrition (underweight, fertility, diet diversity, child illness), and household/environment (dependency ratio, wealth, food security, shocks, water, sanitation). Survey-adjusted multivariate logistic and ordinary least squares regression models were fit to examine predictors of CMD or SRQ score. On average, mothers were 26 (range 18-46) years old and their children were 15 (range 6-24) months old. CMD defined as ≥ 8 positive SRQ responses were reported by 262 women (16%). Protective factors included being engaged in agricultural labor as a main occupation relative to being a housewife (AOR 0.18, 95% CI 0.10-0.32), more time working (0.85, 0.77-0.93), higher decision-making (0.33, 0.16-0.69), SHG membership (0.73, 0.56-0.96), and having an improved toilet (0.49, 0.33-0.72). Risk factors included food insecurity (1.13, 1.07-1.20) and shocks to non-farm livelihoods (2.04, 1.10-3.78). Practitioners and policymakers should aim to improve food security, economic wellbeing and social capital, such as that created through SHG membership, to improve maternal mental health. Future research should aim to understand why working outside the home, albeit in agricultural work, appears to protect maternal mental health in this context., Competing Interests: The authors have declared that no competing interests exist.

Background: A clear understanding of the effects of housing structure, education, occupation, income, and wealth on malaria can help to better design socioeconomic interventions to control the disease. This literature review summarizes the relationship of housing structure, educational level, occupation, income, and wealth with the epidemiology of malaria in sub-Saharan Africa (SSA)., Methods: A systematic review and meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines. The protocol for this study is registered in PROSPERO (ID=CRD42017056070), an international database of prospectively registered systematic reviews. On January 16, 2016, available literature was searched in PubMed, Embase, CINAHL, and Cochrane Library. All but case studies, which reported prevalence or incidence of Plasmodium infection stratified by socioeconomic status among individuals living in SSA, were included without any limits. Odds Ratio (OR) and Relative Risk (RR), together with 95% CI and p-values were used as effect measures. Heterogeneity was assessed using chi-square, Moran's I2, and tau2 tests. Fixed (I2<30%), random (I2≥30%) or log-linear dose-response model was used to estimate the summary OR or RR., Results: After removing duplicates and screening of titles, abstracts, and full text, 84 articles were found eligible for systematic review, and 75 of them were included in the meta-analyses. Fifty-seven studies were cross-sectional, 12 were prospective cohort, 10 were case-control, and five were randomized control trials. The odds of Plasmodium infection increased among individuals who were living in poor quality houses (OR 2.13, 95% CI 1.56-3.23, I2 = 27.7), were uneducated (OR 1.36, 95% CI 1.19-1.54, I2 = 72.4.0%), and were farmers by occupation (OR 1.48, 95% CI 1.11-1.85, I2 = 0.0%) [p<0.01 for all]. The odds of Plasmodium infection also increased with a decrease in the income (OR 1.02, 95% CI 1.01-1.03, tau2<0.001), and wealth index of individuals (OR 1.25, 95% CI 1.18-1.35, tau2 = 0.028) [p<0.001 for both]. Longitudinal studies also showed an increased risk of Plasmodium infection among individuals who were living in poor quality houses (RR 1.86, 95% CI 1.47-2.25, I2 = 0.0%), were uneducated (OR 1.27, 1.03-1.50, I2 = 0.0%), and were farmers (OR 1.36, 1.18-1.58) [p<0.01 for all]., Conclusions: Lack of education, low income, low wealth, living in poorly constructed houses, and having an occupation in farming may increase risk of Plasmodium infection among people in SSA. Public policy measures that can reduce inequity in health coverage, as well as improve economic and educational opportunities for the poor, will help in reducing the burden of malaria in SSA., Competing Interests: The authors have declared that no competing interests exist.

Improving maternal nutrition practices during pregnancy is essential to save lives and improve health outcomes for both mothers and babies. This paper examines the maternal, household, and health service factors influencing maternal nutrition practices in the context of a large scale maternal, newborn, and child health (MNCH) program in Bangladesh. Data were from a household survey of pregnant (n = 600) and recently delivered women (n = 2,000). Multivariate linear and logistic regression analyses were used to examine the determinants of three outcomes: consumption of iron and folic acid (IFA) tablets, calcium tablets, and diverse diets. Women consumed 94 ± 68 IFA and 82 ± 66 calcium tablets (out of 180 as recommended) during pregnancy, and only half of them consumed an adequately diverse diet. Good nutrition knowledge was the key maternal factor associated with higher consumption of IFA (β = 32.5, 95% CI: 19.5, 45.6) and calcium tablets (β ~31.9, 95% CI: 20.9, 43.0) and diverse diet (OR = 1.8, 95% CI: 1.0-3.1), compared to poor knowledge. Women's self-efficacy in achieving the recommended practices and perception of enabling social norms were significantly associated with dietary diversity. At the household level, women who reported a high level of husband's support were more likely to consume IFA (β = 25.0, 95% CI: 18.0, 32.1) and calcium (β = 26.6, 95% CI: 19.4, 33.7) tablets and diverse diet (OR = 1.9, 95% CI: 1.2, 3.3), compared to those who received low support. Health service factors associated with higher intakes of IFA and calcium tablets were early and more prenatal care visits and receipt of free supplements. Combined exposure to several of these factors was attributed to the consumption of an additional 46 IFA and 53 calcium tablets and 17% higher proportions of women consuming diverse diets. Our study shows that improving knowledge, self-efficacy and perceptions of social norms among pregnant women, and increasing husbands' support, early registration in prenatal care, and provision of free supplements will largely improve maternal nutrition practices.

Little is known about nutrition and well-being indicators of pregnant adolescents and the availability and use of nutrition interventions delivered through maternal, newborn, and child health (MNCH) programs. This study compared the differences between pregnant adolescents and adult pregnant women in services received, and in maternal and child nutrition and health conditions. A survey of 2,000 recently delivered women with infants <6 months of age was carried out in 20 sub-districts in Bangladesh where MNCH program is being implemented. Differences in service use and outcomes between pregnant adolescents and adult women were tested using multivariate regression models. The coverage of antenatal care and nutrition services was similar for adolescent and adult mothers. Compared to adult mothers, adolescent mothers had significantly fewer ownership of assets and lower decision making power. Adolescent mothers weighed significantly less than adult women (45.8 vs 47.1 kg, p = 0.001), and their body mass index was significantly lower (19.7 vs 21.3, p = 0.001). Adolescents recovered later and with greater difficulty after childbirth. Infants of adolescent mothers had significant lower height-for-age z-score (-0.89 vs -0.74, p = 0.04), lower weight-for age z-score (-1.21 vs -1.08, p = 0.02) and higher underweight prevalence (22.4% vs 17.9%, p = 0.04) compared to infants of adult women. In conclusion, this study confirms that adolescent pregnancy poses substantial risks for maternal and infant outcomes, and emphasizes that these risks are significant even where services during pregnancy are available and accessed. A focus on preventing adolescent pregnancy is imperative, while also strengthening health and nutrition services for all pregnant women, whether adult or adolescent.

Background: In 2011, the Bangladesh Government introduced the National Nutrition Services (NNS) by leveraging the existing health infrastructure to deliver nutrition services to pregnant woman and children. This study examined the quality of nutrition services provided during antenatal care (ANC) and management of sick children younger than five years., Methods: Service delivery quality was assessed across three dimensions; structural readiness, process and outcome. Structural readiness was assessed by observing the presence of equipment, guidelines and register/reporting forms in ANC rooms and consulting areas for sick children at 37 primary healthcare facilities in 12 sub-districts. In addition, the training and knowledge relevant to nutrition service delivery of 95 healthcare providers was determined. The process of nutrition service delivery was assessed by observing 381 ANC visits and 826 sick children consultations. Satisfaction with the service was the outcome and was determined by interviewing 541 mothers/caregivers of sick children., Results: Structural readiness to provide nutrition services was higher for ANC compared to management of sick children; 73% of ANC rooms had >5 of the 13 essential items while only 13% of the designated areas for management of sick children had >5 of the 13 essential items. One in five (19%) healthcare providers had received nutrition training through the NNS. Delivery of the nutrition services was poor: <30% of women received all four key antenatal nutrition services, 25% of sick children had their weight checked against a growth-chart and <1% had their height measured. Nevertheless, most mothers/caregivers rated their satisfaction of the service above average., Conclusions: Strengthening the provision of equipment and increasing the coverage of training are imperative to improve nutrition services. Inherent barriers to implementing nutrition services in primary health care, especially high caseloads during the management of sick under-five children, should be considered to identify alternative and appropriate service delivery platforms before nationwide scale up.

Optimal breastfeeding (BF) practices in Ethiopia are far below the government's targets, and complementary feeding practices are poor. The Alive & Thrive initiative aimed to improve infant and young child feeding (IYCF) practices through large-scale implementation of social and behavior change communication interventions in four regions of Ethiopia. The study assessed the effects of the interventions on IYCF practices and anthropometry over time in two regions-Southern Nations, Nationalities and Peoples Region and Tigray. A pre- and post-intervention adequacy evaluation design was used; repeated cross-sectional surveys of households with children aged 0-23.9 mo (n = 1481 and n = 1494) and with children aged 24-59.9 mo (n = 1481 and n = 1475) were conducted at baseline (2010) and endline (2014), respectively. Differences in outcomes over time were estimated using regression models, accounting for clustering and covariates. Plausibility analyses included tracing recall of key messages and promoted foods and dose-response analyses. We observed improvements in most WHO-recommended IYCF indicators. Early BF initiation and exclusive BF increased by 13.7 and 9.4 percentage points (pp), respectively. Differences for timely introduction of complementary foods, minimum dietary diversity (MDD), minimum meal frequency (MMF), minimum acceptable diet (MAD), and consumption of iron-rich foods were 22.2, 3.3, 26.2, 3.5, and 2.7 pp, respectively. Timely introduction and intake of foods promoted by the interventions improved significantly, but anthropometric outcomes did not. We also observed a dose-response association between health post visits and early initiation of BF (OR: 1.8); higher numbers of home visits by community volunteers and key messages recalled were associated with 1.8-4.4 times greater odds of achieving MDD, MMF, and MAD, and higher numbers of radio spots heard were associated with 3 times greater odds of achieving MDD and MAD. The interventions were associated with plausible improvements in IYCF practices, but large gaps in improving children's diets in Ethiopia remain, particularly during complementary feeding., Competing Interests: The authors have declared that no competing interests exist.

Circumsporozoite protein (CSP) is the dominant protein on the surface of Plasmodium sporozoites and plays a critical role in the invasion by sporozoites of hepatocytes. Contacts between CSP and heparin sulfate proteoglycans (HSPGs) lead to the attachment of sporozoites to hepatocytes and trigger signaling events in the parasite that promote invasion of hepatocytes. The precise sequence elements in CSP that bind HSPGs have not been identified. We performed a systematic in vitro analysis to dissect the association between Plasmodium falciparum CSP (PfCSP) and hepatocytes. We demonstrate that interactions between PfCSP and heparin or a cultured hepatoma cell line, HepG2, are mediated primarily by a lysine-rich site in the amino terminus of PfCSP. Importantly, the carboxyl terminus of PfCSP facilitates heparin-binding by the amino-terminus but does not interact directly with heparin. These findings provide insights into how CSP recognizes hepatocytes and useful information for further functional studies of CSP., Competing Interests: The authors have declared that no competing interests exist.

Objective: To conduct a systematic review of studies of social media platforms used by young people to discuss and view deliberate self-harm., Study Design: 11 electronic databases were searched from January 2000 to January 2012 for primary research; in June 2014 an updated search of Medline was conducted. Grey literature sources were also searched. Search results were screened by two reviewers. Data were extracted by one reviewer and verified by another. Methodological quality was assessed using the Mixed Methods Appraisal Tool., Results: Due to heterogeneity in study objectives and outcomes, results were not pooled; a narrative analysis is presented. 26 studies were included. Most were conducted in Canada or the UK (30.8% each), used qualitative designs (42.3%), and evaluated discussion forums (73.1%). Participants were most often aged 19-21 years (69.2%), female (mean 68.6%), and 19.2% had a documented history of depression. The social media platforms evaluated were commonly supportive and provided a sense of community among users. Support included suggestions for formal treatment, advice on stopping self-harming behavior, and encouragement. Harms included normalizing and accepting self-harming behavior; discussion of motivation or triggers, concealment, suicidal ideation or plans; and live depictions of self-harm acts., Conclusions: Although this evidence is limited by its descriptive nature, studies identify beneficial and detrimental effects for young people using social media to discuss and view deliberate self-harm. The connections users make online may be valuable to explore for therapeutic benefit. Prospective, longitudinal investigations are needed to identify short- and long-term potential harms associated with use.

Cupin superfamily is one of the most diverse super families. This study reports the purification and characterization of a novel cupin domain containing protease from rice bran for the first time. Hypothetical protein OsI&#95;13867 was identified and named as cupincin. Cupincin was purified to 4.4 folds with a recovery of 4.9%. Cupincin had an optimum pH and temperature of pH 4.0 and 60 °C respectively. Cupincin was found to be a homotrimer, consisting of three distinct subunits with apparent molecular masses of 33.45 kDa, 22.35 kDa and 16.67 kDa as determined by MALDI-TOF, whereas it eluted as a single unit with an apparent molecular mass of 135.33 ± 3.52 kDa in analytical gel filtration and migrated as a single band in native page, suggesting its homogeneity. Sequence identity of cupincin was deduced by determining the amino-terminal sequence of the polypeptide chains and by and de novo sequencing. For understanding the hydrolysing mechanism of cupincin, its three-dimensional model was developed. Structural analysis indicated that cupincin contains His313, His326 and Glu318 with zinc ion as the putative active site residues, inhibition of enzyme activity by 1,10-phenanthroline and atomic absorption spectroscopy confirmed the presence of zinc ion. The cleavage specificity of cupincin towards oxidized B-chain of insulin was highly specific; cleaving at the Leu15-Tyr16 position, the specificity was also determined using neurotensin as a substrate, where it cleaved only at the Glu1-Tyr2 position. Limited proteolysis of the protease suggests a specific function for cupincin. These results demonstrated cupincin as a completely new protease.

Adequate utilization of services is critical to maximize the impact of counselling on infant and young child feeding (IYCF), but little is known about factors affecting utilization. Our study examined supply- and demand-side factors associated with the utilization of IYCF counselling services in Viet Nam. We used survey data from mothers with children <2y (n = 1,008) and health staff (n = 60) from the evaluation of a program that embedded IYCF counseling into the existing government health system. The frequency of never users, one-time users, repeat users, and achievers of the recommended minimum number of visits at health facilities were 45.1%, 13.0%, 28.4% and 13.5%, respectively. Poisson regression showed that demand-generation strategies, especially invitation cards, were the key factors determining one-time use (Prevalence ratio, PR 3.0, 95% CI: 2.2-4.2), repeated use (PR 3.2, 95% CI: 2.4-4.2), and achievement of minimum visits (PR 5.5, 95% CI: 3.6-8.4). Higher maternal education was associated with higher utilization both for one-time and repeated use. Being a farmer, belonging to an ethnic minority, and having a wasted child were associated with greater likelihood of achieving the minimum recommended number of visits, whereas child stunting or illness were not. Distance to health center was a barrier to repeated visits. Among supply-side factors, good counselling skills (PR: 1.3-1.8) was the most important factor associated with any service use, whereas longer employment duration and greater work pressure of health center staff were associated with lower utilization. Population attributable risk estimations showed that an additional 25% of the population would have achieved the minimum number of visits if exposed to three demand-generation strategies, and further increased to 49% if the health staff had good counseling skills and low work pressure. Our study provides evidence that demand-generation strategies are essential to increase utilization of facility-based IYCF counselling services in Viet Nam, and may be relevant for increasing and sustaining use of nutrition services in similar contexts.

Background: Haiti has the highest number of people living with HIV infection in the Caribbean/Latin America region. Medical male circumcision (MMC) has been recommended to help prevent the spread of HIV. We sought to assess knowledge, attitudes, practices and beliefs about MMC among a sample of health care providers in Haiti., Methods: A convenience sample of 153 health care providers at the GHESKIO Centers in Haiti responded to an exploratory survey that collected information on several topics relevant to health providers about MMC. Descriptive statistics were calculated for the responses and multivariable logistic regression was conducted to determine opinions of health care providers about the best age to perform MMC on males. Bayesian network analysis and sensitivity analysis were done to identify the minimum level of change required to increase the acceptability of performing MMC at age less than 1 year., Results: The sample consisted of medical doctors (31.0%), nurses (49.0%), and other health care professionals (20.0%). Approximately 76% showed willingness to offer MMC services if they received training. Seventy-six percent believed that their male patients would accept circumcision, and 59% believed infancy was the best age for MMC. More than 90% of participants said that MMC would reduce STIs. Physicians and nurses who were willing to offer MMC if provided with adequate training were 2.5 (1.15-5.71) times as likely to choose the best age to perform MMC as less than one year. Finally, if the joint probability of choosing "the best age to perform MMC" as one year or older and having the mistaken belief that "MMC prevents HIV entirely" is reduced by 63% then the probability of finding that performing MMC at less than one year acceptable to health care providers is increased by 35%., Conclusion: Participants demonstrated high levels of knowledge and positive attitudes towards MMC. Although this study suggests that circumcision is acceptable among certain health providers in Haiti, studies with larger and more representative samples are needed to confirm this finding.

The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR labeled cells were injected via tail vein in mice bearing 4T1 tumors in the flank. In some cases labeled 4T1 specific T-lymphocytes were injected a week before 4T1 tumor cell implantation. Multi-spectral in vivo fluorescence imaging was done to subtract the autofluorescence and isolate the near infrared signal carried by the T-lymphocytes. In recipient mice with established 4T1 tumors, labeled 4T1 specific T-lymphocytes showed marked tumor retention, which peaked 6 days post infusion and persisted at the tumor site for up to 3 weeks. When 4T1 tumor cells were implanted 1-week post-infusion of labeled T-lymphocytes, T-lymphocytes responded to the immunologic challenge and accumulated at the site of 4T1 cell implantation within two hours and the signal persisted for 2 more weeks. Tumor accumulation of labeled 4T1 specific T-lymphocytes was absent in mice bearing Meth A sarcoma tumors. When lysate of 4T1 specific labeled T-lymphocytes was injected into 4T1 tumor bearing mice the near infrared signal was not detected at the tumor site. In conclusion, our validated results confirm that the near infrared signal detected at the tumor site represents the DiR labeled 4T1 specific viable T-lymphocytes and their response to immunologic challenge can be imaged in vivo.

We show that humpback-whale vocalization behavior is synchronous with peak annual Atlantic herring spawning processes in the Gulf of Maine. With a passive, wide-aperture, densely-sampled, coherent hydrophone array towed north of Georges Bank in a Fall 2006 Ocean Acoustic Waveguide Remote Sensing (OAWRS) experiment, vocalizing whales could be instantaneously detected and localized over most of the Gulf of Maine ecosystem in a roughly 400-km diameter area by introducing array gain, of 18 dB, orders of magnitude higher than previously available in acoustic whale sensing. With humpback-whale vocalizations consistently recorded at roughly 2000/day, we show that vocalizing humpbacks (i) were overwhelmingly distributed along the northern flank of Georges Bank, coinciding with the peak spawning time and location of Atlantic herring, and (ii) their overall vocalization behavior was strongly diurnal, synchronous with the formation of large nocturnal herring shoals, with a call rate roughly ten-times higher at night than during the day. Humpback-whale vocalizations were comprised of (1) highly diurnal non-song calls, suited to hunting and feeding behavior, and (2) songs, which had constant occurrence rate over a diurnal cycle, invariant to diurnal herring shoaling. Before and during OAWRS survey transmissions: (a) no vocalizing whales were found at Stellwagen Bank, which had negligible herring populations, and (b) a constant humpback-whale song occurrence rate indicates the transmissions had no effect on humpback song. These measurements contradict the conclusions of Risch et al. Our analysis indicates that (a) the song occurrence variation reported in Risch et al. is consistent with natural causes other than sonar, (b) the reducing change in song reported in Risch et al. occurred days before the sonar survey began, and (c) the Risch et al. method lacks the statistical significance to draw the conclusions of Risch et al. because it has a 98-100% false-positive rate and lacks any true-positive confirmation.

Genome-wide participation and importance of the histone chaperone Asf1 (Anti-Silencing Function 1) in diverse DNA transactions like replication, repair, heterochromatic silencing and transcription are well documented. Yet its genome-wide targets have not been reported. Using ChIP-seq method, we found that yeast Asf1 associates with 590 unique targets including centromeres, telomeres and condensin-binding sites. It is found selectively on highly transcribed regions, which include replication fork pause sites. Asf1 preferentially associates with the genes transcribed by RNA polymerase (pol) III where its presence affects RNA production and replication-independent histone exchange. On pol II-transcribed genes, a negative correlation is found between Asf1 and nucleosome occupancy. It is not enriched on most of the reported sites of histone exchange or on the genes, which are misregulated in the asf1Δ cells. Interestingly, chromosome-wide distributions of Asf1 and one of the condensin subunits, Brn1 show a nearly identical pattern. Moreover, Brn1 shows reduced occupancy at various condensin-binding sites in asf1Δ cells. These results along with high association of Asf1 with heterochromatic centromeres and telomeres ascribe novel roles to Asf1 in condensin loading and chromatin dynamics.

Fungi contribute substantially to biogeochemical cycles of terrestrial and marine habitats by decomposing matter and recycling nutrients. Yet, the diversity of their planktonic forms in the open ocean is poorly described. In this study, culture-independent and molecular approaches were applied to investigate fungal diversity and abundance derived from samples collected from a broad swath of the Pacific Warm Pool across major environmental gradients Our results revealed that planktonic fungi were molecularly diverse and their diversity patterns were related to major phytoplankton taxa and various nutrients including nitrate, nitrite, orthophosphate and silicic acid. Over 400 fungal phylotypes were recovered across this region and nearly half of them grouped into two major fungal lineages of Ascomycota and Basidiomycota, whose abundance varied among stations. These results suggest that planktonic fungi are a diverse and integral component of the marine microbial community and should be included in future marine microbial ecosystem models.

Background/aims: The importance of sperm capacitation for mammalian fertilization has been confirmed in the present study via sperm metabolism. Involvement of the metabolic enzymes pyruvate dehydrogenase complex (PDHc) and its E3 subunit, dihydrolipoamide dehydrogenase (DLD) in hamster in vitro fertilization (IVF) via in vitro sperm capacitation is being proposed through regulation of sperm intracellular lactate, pH and calcium., Methodology and Principal Findings: Capacitated hamster spermatozoa were allowed to fertilize hamster oocytes in vitro which were then assessed for fertilization, microscopically. PDHc/DLD was inhibited by the use of the specific DLD-inhibitor, MICA (5-methoxyindole-2-carboxylic acid). Oocytes fertilized with MICA-treated (MT) [and thus PDHc/DLD-inhibited] spermatozoa showed defective fertilization where 2nd polar body release and pronuclei formation were not observed. Defective fertilization was attributable to capacitation failure owing to high lactate and low intracellular pH and calcium in MT-spermatozoa during capacitation. Moreover, this defect could be overcome by alkalinizing spermatozoa, before fertilization. Increasing intracellular calcium in spermatozoa pre-IVF and in defectively-fertilized oocytes, post-fertilization rescued the arrest seen, suggesting the role of intracellular calcium from either of the gametes in fertilization. Parallel experiments carried out with control spermatozoa capacitated in medium with low extracellular pH or high lactate substantiated the necessity of optimal sperm intracellular lactate levels, intracellular pH and calcium during sperm capacitation, for proper fertilization., Conclusions: This study confirms the importance of pyruvate/lactate metabolism in capacitating spermatozoa for successful fertilization, besides revealing for the first time the importance of sperm PDHc/ DLD in fertilization, via the modulation of sperm intracellular lactate, pH and calcium during capacitation. In addition, the observations made in the IVF studies in hamsters suggest that capacitation failures could be a plausible cause of unsuccessful fertilization encountered during human assisted reproductive technologies, like IVF and ICSI. Our studies indicate a role of sperm capacitation in the post-penetration events during fertilization.

Cytotoxic lymphocytes (CTL) have been reported to show a range of motility patterns from rapid long-range tracking to complete arrest, but how and whether these kinematics affect their ability to kill target cells is not known. Many in vitro killing assays utilize cell lines and tumour-derived cells as targets, which may be of limited relevance to the kinetics of CTL-mediated killing of somatic cells. Here, live-cell microscopy is used to examine the interactions of CTL and primary murine skin cells presenting antigens. We developed a qualitative and quantitative killing assay using extended-duration fluorescence time-lapse microscopy coupled with large-volume objective software-based data analysis to obtain population data of cell-to-cell interactions, motility and apoptosis. In vivo and ex vivo activated antigen-specific cytotoxic lymphocytes were added to primary keratinocyte targets in culture with fluorometric detection of caspase-3 activation in targets as an objective determinant of apoptosis. We found that activated CTL achieved contact-dependent apoptosis of non-tumour targets after a period of prolonged attachment - on average 21 hours - which was determined by target cell type, amount of antigen, and activation status of CTL. Activation of CTL even without engagement of the T cell receptor was sufficient to mobilise cells significantly above baseline, while the addition of cognate antigen further enhanced their motility. Highly activated CTL showed markedly increased vector displacement, and velocity, and lead to increased antigen-specific target cell death. These data show that the inherent kinematics of CTL correlate directly with their ability to kill non-tumour cells presenting cognate antigen.

Background: 15% of reproducing couples suffer from pregnancy loss(PL) and recurs in 2-3%. One of the most frequently hypothesized causes of unexplained PL refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Hereditary thrombophilia and antiphospholipid antibodies have been extensively described as risk factors for PL in women with unknown aetiology. Recently, a new marker has emerged: the cell-derived procoagulant circulating microparticles(MPs) which have been reported to have a major role in many thrombosis complicated diseases. This study aims to analyze the significance of procoagulant MPs in women suffering from unexplained recurrent pregnancy loss(RPL), and characterize their cellular origin., Method and Findings: 115 women with RPL were analyzed for common thrombophilia markers and different cell derived MPs-total annexinV, platelet(CD41a), endothelial(CD146,CD62e), leukocyte(CD45), erythrocyte(CD235a) and tissue factor(CD142)(TF) expressing MPs and were compared with 20 healthy non-pregnant women. Methodology for MP analysis was standardized by participating in the "Vascular Biology Scientific and Standardization Committee workshop"., Results: Total annexinV, TF and endothelial MPs were found significantly increased(p<0.05, 95% confidence interval) in women with RPL. The procoagulant activity of MPs measured by STA-PPL clotting time assay was found in correspondence with annexinV MP levels, wherein the clot time was shortened in samples with increased MP levels. Differences in platelet, leukocyte and erythrocyte derived MPs were not significant. Thirty seven of 115 women were found to carry any of the acquired or hereditary thrombophilia markers. No significant differences were seen in the MP profile of women with and without thrombophilia marker., Conclusion: The presence of elevated endothelial, TF and phosphatidylserine expressing MPs at a distance (at least 3 months) from the PL suggests a continued chronic endothelial damage/activation which may get exaggerated at the onset of pregnancy. The data suggests that MPs may contribute to uteroplacental thrombosis and are associated with the pathogenesis of RPL.

Plasmodium Calcium Dependent Protein Kinase (CDPK1) is required for the development of sexual stages in the mosquito. In addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. We demonstrate that Plasmodium berghei CDPK1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. We successfully disrupted P. berghei CDPK1 (PbCDPK1) by homologous recombination. The recovery of erythrocytic stage parasites lacking PbCDPK1 (PbCDPK1-) demonstrated that PbCDPK1 is not essential for erythrocytic invasion or intra-erythrocytic development. To study PbCDPK1's role in sporozoites and liver stage parasites, we generated a conditional mutant (CDPK1 cKO). Phenotypic characterization of CDPK1 cKO sporozoites demonstrated that CDPK1 is redundant or dispensable for the invasion of mammalian hepatocytes, the egress of parasites from infected hepatocytes and through the subsequent erythrocytic cycle. We conclude that P. berghei CDPK1 plays an essential role only in the mosquito sexual stages.

Background: The search for molecules against Mycobacterium tuberculosis is urgent. The mechanisms facilitating the intra-macrophage survival of Mycobacterium tuberculosis are as yet not entirely understood. However, there is evidence showing the involvement of host cell cytoskeleton in every step of establishment and persistence of mycobacterial infection., Methodology/principal Findings: Here we show that expression of ARPC4, a subunit of the Actin related protein 2/3 (Arp2/3) protein complex, severely affects the pathogen's growth. TEM studies display shedding of the mycobacterial outer-coat. Furthermore, in infected macrophages, mycobacteria expressing ARPC4 were cleared off at a much faster rate, and were unable to mount a pro-inflammatory cytokine response. The translocation of ARPC4-expressing mycobacteria to the lysosome of the infected macrophage was also impaired. Additionally, the ARPC4 subunit was shown to interact with Rv1626, an essential secretory mycobacterial protein. Real-time PCR analysis showed that upon expression of ARPC4 in mycobacteria, Rv1626 expression is downregulated as much as six-fold. Rv1626 was found to also interact with mammalian cytoskeleton protein, Arp2/3, and enhance the rate of actin polymerization., Conclusions/significance: With crystal structures for Rv1626 and ARPC4 subunit already known, our finding lays out the effect of a novel molecule on mycobacteria, and represents a viable starting point for developing potent peptidomimetics.

Background: The influence of multiple maternal and pregnancy characteristics on offspring cardiometabolic traits at birth is not well understood and was evaluated in this study., Methods and Findings: The Family Atherosclerosis Monitoring In earLY life (FAMILY) Study prospectively evaluated 11 cardiometabolic traits in 901 babies born to 857 mothers. The influence of maternal age, health (pre-pregnancy weight, blood pressure, glycemic status, lipids), health behaviors (diet, activity, smoking) and pregnancy characteristics (gestational age at birth, gestational weight gain and placental-fetal ratio) were examined. Greater gestational age influenced multiple newborn cardiometabolic traits including cord blood lipids, glucose and insulin, body fat and blood pressure. In a subset of 442 singleton mother/infant pairs, principal component analysis grouped 11 newborn cardiometabolic traits into 5 components (anthropometry/insulin, 2 lipid components, blood pressure and glycemia), accounting for 74% of the variance of the 11 outcome variables. Determinants of these components, corrected for sex and gestational age, were examined. Baby anthropometry/insulin was independently predicted by higher maternal pre-pregnancy weight (standardized estimate 0.30) and gestational weight gain (0.30; both p<0.0001) and was inversely related to smoking during pregnancy (-0.144; p = 0.01) and maternal polyunsaturated to saturated fat intake (-0.135;p = 0.01). Component 2 (HDL-C/Apo Apolipoprotein1) was inversely associated with maternal age. Component 3 (blood pressure) was not clustered with any other newborn cardiometabolic trait and no associations with maternal pregnancy characteristics were identified. Component 4 (triglycerides) was positively associated with maternal hypertension and triglycerides, and inversely associated with maternal HDL and age. Component 5 (glycemia) was inversely associated with placental/fetal ratio (-0.141; p = 0.005). LDL-C was a bridging variable between the lipid factors and glycemia., Conclusions: Maternal health, health behaviours and placenta to fetal weight ratio are associated with newborn cardiometabolic traits over and above gestational age. Future investigations are needed to determine if these factors remain important determinants of cardiometabolic health throughout childhood.

Prostate cancer is influenced by epigenetic modification of genes involved in cancer development and progression. Increased expression of Prostate Stem Cell Antigen (PSCA) is correlated with development of malignant human prostate cancer, while studies in mouse models suggest that decreased PSCA levels promote prostate cancer metastasis. These studies suggest that PSCA has context-dependent functions, and could be differentially regulated during tumor progression. In the present study, we identified the multi-functional transcription factor Yin Yang 1 (YY1) as a modulator of PSCA expression in prostate epithelial cell lines. Increased YY1 levels are observed in prostatic intraepithelial neoplasia (PIN) and advanced disease. We show that androgen-mediated up-regulation of PSCA in prostate epithelial cell lines is dependent on YY1. We identified two direct YY1 binding sites within the PSCA promoter, and showed that the upstream site inhibited, while the downstream site, proximal to the androgen-responsive element, stimulated PSCA promoter activity. Thus, changes in PSCA expression levels in prostate cancer may at least partly be affected by cellular levels of YY1. Our results also suggest multiple roles for YY1 in prostate cancer which may contribute to disease progression by modulation of genes such as PSCA.

Background: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown., Principal Findings: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection., Significance: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection.

Background: The H19/Igf2 imprinting control region (ICR) functions as an insulator exclusively in the unmethylated maternal allele, where enhancer-blocking by CTCF protein prevents the interaction between the Igf2 promoter and the distant enhancers. DNA methylation inhibits CTCF binding in the paternal ICR allele. Two copies of the chicken β-globin insulator (ChβGI)(2) are capable of substituting for the enhancer blocking function of the ICR. Insulation, however, now also occurs upon paternal inheritance, because unlike the H19 ICR, the (ChβGI)(2) does not become methylated in fetal male germ cells. The (ChβGI)(2) is a composite insulator, exhibiting enhancer blocking by CTCF and chromatin barrier functions by USF1 and VEZF1. We asked the question whether these barrier proteins protected the (ChβGI)(2) sequences from methylation in the male germ line., Methodology/principal Findings: We genetically dissected the ChβGI in the mouse by deleting the binding sites USF1 and VEZF1. The methylation of the mutant versus normal (ChβGI)(2) significantly increased from 11% to 32% in perinatal male germ cells, suggesting that the barrier proteins did have a role in protecting the (ChβGI)(2) from methylation in the male germ line. Contrary to the H19 ICR, however, the mutant (mChβGI)(2) lacked the potential to attain full de novo methylation in the germ line and to maintain methylation in the paternal allele in the soma, where it consequently functioned as a biallelic insulator. Unexpectedly, a stricter enhancer blocking was achieved by CTCF alone than by a combination of the CTCF, USF1 and VEZF1 sites, illustrated by undetectable Igf2 expression upon paternal transmission., Conclusions/significance: In this in vivo model, hypomethylation at the ICR position together with fetal growth retardation mimicked the human Silver-Russell syndrome. Importantly, late fetal/perinatal death occurred arguing that strict biallelic insulation at the H19/Igf2 ICR position is not tolerated in development.

Knowledge of specific domain-domain interactions (DDIs) is essential to understand the functional significance of protein interaction networks. Despite the availability of an enormous amount of data on protein-protein interactions (PPIs), very little is known about specific DDIs occurring in them. Here, we present a top-down approach to accurately infer functionally relevant DDIs from PPI data. We created a comprehensive, non-redundant dataset of 209,165 experimentally-derived PPIs by combining datasets from five major interaction databases. We introduced an integrated scoring system that uses a novel combination of a set of five orthogonal scoring features covering the probabilistic, evolutionary, evidence-based, spatial and functional properties of interacting domains, which can map the interacting propensity of two domains in many dimensions. This method outperforms similar existing methods both in the accuracy of prediction and in the coverage of domain interaction space. We predicted a set of 52,492 high-confidence DDIs to carry out cross-species comparison of DDI conservation in eight model species including human, mouse, Drosophila, C. elegans, yeast, Plasmodium, E. coli and Arabidopsis. Our results show that only 23% of these DDIs are conserved in at least two species and only 3.8% in at least 4 species, indicating a rather low conservation across species. Pair-wise analysis of DDI conservation revealed a 'sliding conservation' pattern between the evolutionarily neighboring species. Our methodology and the high-confidence DDI predictions generated in this study can help to better understand the functional significance of PPIs at the modular level, thus can significantly impact further experimental investigations in systems biology research.