Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits.

The cardiac transcription factor (TF) gene NKX2-5 has been associated with electrocardiographic (EKG) traits through genome-wide association studies (GWASs), but the extent to which differential binding of NKX2-5 at common regulatory variants contributes to these traits has not yet been studied. We analyzed transcriptomic and epigenomic data from induced pluripotent stem cell-derived cardiomyocytes from seven related individuals, and identified ~2,000 single-nucleotide variants associated with allele-specific effects (ASE-SNVs) on NKX2-5 binding. NKX2-5 ASE-SNVs were enriched for altered TF motifs, for heart-specific expression quantitative trait loci and for EKG GWAS signals. Using fine-mapping combined with epigenomic data from induced pluripotent stem cell-derived cardiomyocytes, we prioritized candidate causal variants for EKG traits, many of which were NKX2-5 ASE-SNVs. Experimentally characterizing two NKX2-5 ASE-SNVs (rs3807989 and rs590041) showed that they modulate the expression of target genes via differential protein binding in cardiac cells, indicating that they are functional variants underlying EKG GWAS signals. Our results show that differential NKX2-5 binding at numerous regulatory variants across the genome contributes to EKG phenotypes

The power of narrative persuasion: how an entertainment-education serial drama tackled open defecation and promoted contraceptive use in India

Television and radio serial dramas have been used as an effective entertainment-education (EE) strategy to address complex health and social issues around the world. In this article, we analyse India’s experience with the EE television serial, Main Kuch Bhi Kar Sakti HoonSeason 3 (I, A Woman, Can Achieve Anything, hereafter MKBKSH-3), broadcasted in 2019. Produced by Population Foundation of India, MKBKSH-3purposely employed principles of narrative persuasion to tackle open defecation, promote contraceptive use, and advocate for gender equality in a deeply entrenched patriarchal system. As part of a larger programme evaluation, we conducted data collection using two complementary methods: (1) field experiments in Uttar Pradesh’s Kanpur Dehat district with repeated measures among viewers and non-viewers; and (2) viewer surveys through the popular interactive voice response system with callers from across 28 states and union territories. Wherever possible, we kept questions consistent to help triangulate research findings. Our results indicate a significant increase in toilet ownership and decrease in open defecation among MKBKSH-3viewers. Further, MKBKSH-3’scharacters and storylines helped raise awareness of injectable contraceptives, and viewers—both male and female—displayed an increased likelihood of moving toward adopting contraceptives that were promoted. These empirical findings add to the growing literature on the value of entertainment-education serial dramas as enabling media for social and behaviour change.publishedVersio

An Artificial Intelligence Chatbot for Young People’s Sexual and Reproductive Health in India (SnehAI): Instrumental Case Study

Background: Leveraging artificial intelligence (AI)–driven apps for health education and promotion can help in the accomplishment of several United Nations sustainable development goals. SnehAI, developed by the Population Foundation of India, is the first Hinglish (Hindi + English) AI chatbot, deliberately designed for social and behavioral changes in India. It provides a private, nonjudgmental, and safe space to spur conversations about taboo topics (such as safe sex and family planning) and offers accurate, relatable, and trustworthy information and resources. Objective: This study aims to use the Gibson theory of affordances to examine SnehAI and offer scholarly guidance on how AI chatbots can be used to educate adolescents and young adults, promote sexual and reproductive health, and advocate for the health entitlements of women and girls in India. Methods: We adopted an instrumental case study approach that allowed us to explore SnehAI from the perspectives of technology design, program implementation, and user engagement. We also used a mix of qualitative insights and quantitative analytics data to triangulate our findings. Results: SnehAI demonstrated strong evidence across fifteen functional affordances: accessibility, multimodality, nonlinearity, compellability, queriosity, editability, visibility, interactivity, customizability, trackability, scalability, glocalizability, inclusivity, connectivity, and actionability. SnehAI also effectively engaged its users, especially young men, with 8.2 million messages exchanged across a 5-month period. Almost half of the incoming user messages were texts of deeply personal questions and concerns about sexual and reproductive health, as well as allied topics. Overall, SnehAI successfully presented itself as a trusted friend and mentor; the curated content was both entertaining and educational, and the natural language processing system worked effectively to personalize the chatbot response and optimize user experience. Conclusions: SnehAI represents an innovative, engaging, and educational intervention that enables vulnerable and hard-to-reach population groups to talk and learn about sensitive and important issues. SnehAI is a powerful testimonial of the vital potential that lies in AI technologies for social good

The power of narrative persuasion: how an entertainment-education serial drama tackled open defecation and promoted contraceptive use in India

Television and radio serial dramas have been used as an effective entertainment-education (EE) strategy to address complex health and social issues around the world. In this article, we analyse India’s experience with the EE television serial, Main Kuch Bhi Kar Sakti HoonSeason 3 (I, A Woman, Can Achieve Anything, hereafter MKBKSH-3), broadcasted in 2019. Produced by Population Foundation of India, MKBKSH-3purposely employed principles of narrative persuasion to tackle open defecation, promote contraceptive use, and advocate for gender equality in a deeply entrenched patriarchal system. As part of a larger programme evaluation, we conducted data collection using two complementary methods: (1) field experiments in Uttar Pradesh’s Kanpur Dehat district with repeated measures among viewers and non-viewers; and (2) viewer surveys through the popular interactive voice response system with callers from across 28 states and union territories. Wherever possible, we kept questions consistent to help triangulate research findings. Our results indicate a significant increase in toilet ownership and decrease in open defecation among MKBKSH-3viewers. Further, MKBKSH-3’scharacters and storylines helped raise awareness of injectable contraceptives, and viewers—both male and female—displayed an increased likelihood of moving toward adopting contraceptives that were promoted. These empirical findings add to the growing literature on the value of entertainment-education serial dramas as enabling media for social and behaviour change

Global Survey of Outcomes of Neurocritical Care Patients: Analysis of the PRINCE Study Part 2

BACKGROUND: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study. METHODS: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality. RESULTS: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47). CONCLUSION: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.status: publishe