PIWI proteins are essential for early Drosophila embryogenesis

AbstractPIWI proteins, a subfamily of the ARGONAUTE/PIWI protein family, have been implicated in transcriptional and posttranscriptional gene regulation and transposon silencing mediated by small non-coding RNAs, especially piRNAs. Although these proteins are known to be required for germline development, their somatic function remains elusive. Here, we examine the maternal function of all three PIWI proteins in Drosophila; Piwi, Aubergine (Aub) and Argonaute3 (Ago3) during early embryogenesis. In syncytial embryos, Piwi displays an embryonic stage-dependent localization pattern. Piwi is localized in the cytoplasm during mitotic cycles 1–10. Between cycles 11 and 14, Piwi remains in the cytoplasm during mitosis but moves into the somatic nucleus during interphase. Beyond cycle 14, it stays in the nucleus. Aub and Ago3 are diffusely cytoplasmic from cycle 1 to 14. Embryos maternally depleted of any one of the three PIWI proteins display severe mitotic defects, including abnormal chromosome and nuclear morphology, cell cycle arrest, asynchronous nuclear division and aberrant nuclear migration. Furthermore, all three PIWI proteins are required for the assembly of mitotic machinery and progression through mitosis. Embryos depleted of maternal PIWI proteins also exhibit chromatin organization abnormalities. These observations indicate that maternal Piwi, Aub and Ago3 play a critical role in the maintenance of chromatin structure and cell cycle progression during early embryogenesis, with compromised chromatin integrity as a possible cause of the observed mitotic defects. Our study demonstrates the essential function of PIWI proteins in the first phase of somatic development

Effects of an mHealth intervention for community health workers on maternal and child nutrition and health service delivery in India: protocol for a quasi-experimental mixed-methods evaluation.

INTRODUCTION:Millions of children in India still suffer from poor health and under-nutrition, despite substantial improvement over decades of public health programmes. The Anganwadi centres under the Integrated Child Development Scheme (ICDS) provide a range of health and nutrition services to pregnant women, children <6 years and their mothers. However, major gaps exist in ICDS service delivery. The government is currently strengthening ICDS through an mHealth intervention called Common Application Software (ICDS-CAS) installed on smart phones, with accompanying multilevel data dashboards. This system is intended to be a job aid for frontline workers, supervisors and managers, aims to ensure better service delivery and supervision, and enable real-time monitoring and data-based decision-making. However, there is little to no evidence on the effectiveness of such large-scale mHealth interventions integrated with public health programmes in resource-constrained settings on the service delivery and subsequent health and nutrition outcomes. METHODS AND ANALYSIS:This study uses a village-matched controlled design with repeated cross-sectional surveys to evaluate whether ICDS-CAS can enable more timely and appropriate services to pregnant women, children <12 months and their mothers, compared with the standard ICDS programme. The study will recruit approximately 1500 Anganwadi workers and 6000+ mother-child dyads from 400+ matched-pair villages in Bihar and Madhya Pradesh. The primary outcomes are the proportion of beneficiaries receiving (a) adequate number of home visits and (b) appropriate level of counselling by the Anganwadi workers. Secondary outcomes are related to improvements in other ICDS services, and knowledge and practices of the Anganwadi workers and beneficiaries. ETHICS AND DISSEMINATION:Ethical oversight is provided by the Committee for the Protection of Human Subjects at the University of California at Berkeley, and the Suraksha Independent Ethics Committee in India. The results will be published in peer-reviewed journals and analysis data will be made public. TRIAL REGISTRATION NUMBER:ISRCTN83902145

Own and Parents’ Schooling as Predictors of Cognition: Findings from the Longitudinal Chilean Social Protection Survey

A large literature on the predictive powers of own schooling, and increasingly one’s parents’ schooling on cognitive and physical health of aging individuals focuses on high-income countries. There is a paucity of studies for other contexts, including Latin America and the Caribbean (LAC). We use data from the longitudinal Chilean Social Protection Survey to investigate associations between one’s own schooling, one’s parents’ schooling, childhood family economic status and cognition of aging adults in a country that differs substantially from the U.S. and from other LAC countries. We further test whether these associations differ by gender. Our estimates suggest that own schooling significantly predicts cognition and that parental (particularly maternal) schooling and childhood family socioeconomic status are significant predictors of cognition. We also find significant heterogeneities in associations between the respondents’ own schooling and cognition for women and men

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools.Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naive men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI.Design, setting, and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected.Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4.Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and over-estimation of csPCa in the PROMOD cohort.Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making.Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online. Crown Copyright (C) 2022 Published by Elsevier B.V. on behalf of European Association of Urology.</p

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Epigenetic changes and assisted reproductive technologies

Children conceived by Assisted Reproductive Technologies (ART) are at moderately increased risk for a number of undesirable outcomes, including low birth weight. Whether the additional risk is associated with specific procedures used in ART or biological factors that are intrinsic to infertility has been the subject of much debate, as has the mechanism by which ART or infertility might influence this risk. The potential effect of ART clinical and laboratory procedures on the gamete and embryo epigenomes heads the list of mechanistic candidates that might explain the association between ART and undesirable clinical outcomes. The reason for this focus is that the developmental time points at which ART clinical and laboratory procedures are implemented are precisely the time points at which large-scale reorganization of the epigenome takes place during normal development. In this manuscript, we review the many human studies comparing the epigenomes of ART children with children conceived in vivo, as well as assess the potential of individual ART clinical and laboratory procedures to alter the epigenome

Ophthalmological and radiological findings in patients of hypertensive crisis reporting to an intensive care setting

Background: The term “hypertensive crisis (HC)” is used to describe both hypertensive emergencies and hypertensive urgencies. Hypertensive emergencies are characterized by the presence of target organ damage, whereas hypertensive urgencies do not involve such organ damage. Methods: The main objective of this research was to evaluate all prevalence and clinical profiles of HC in an intensive care unit (ICU). A consecutive type of nonprobability sampling was followed during the study period for the selection of the study sample. A total of 50 patients fulfilling the criteria of eligibility were used for this research with proper informed consent. Results: Of the 50 patients reporting to the ICU with hypertensive emergencies and urgency, the most common systemic involvement was neurological, followed by cardiac. On Electrocardiographic (ECG), ST-T wave changes were seen in 46% of cases, whereas left ventricular hypertrophy was reported in 22% of cases. Conclusions: Hypertensive retinopathy was the most common ophthalmological finding, SR-T wave changes were the most common ECG finding, and intracerebral hemorrhage was the most common computed tomography finding in patients of HC

Improving nutrition in Telangana: Insights from the current status of outcomes, determinants and interventions in 2016

The purpose of this Policy Note is to examine the current status of undernutrition in Telangana and to document geographic variability in the major determinants of nutrition and the coverage of key nutrition and health interventions. In doing this analysis, we aim to highlight the key areas of action to improve nutrition in Telangana.Non-PRIFPRI1; POSHAN; F Strengthening institutions and governance; CRP4PHND; SAO; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH

Improving nutrition in Uttar Pradesh: Insights from examining trends in outcomes, determinants and interventions between 2006 and 2016

The purpose of this Policy Note is to examine the trends in undernutrition in Uttar Pradesh and to document trends and geographic variability in the major determinants of nutrition and the coverage of key nutrition and health interventions. In doing this analysis, we aim to highlight key areas for actions to improve nutrition in Uttar Pradesh.Non-PRIFPRI1; POSHAN; F Strengthening institutions and governance; CRP4SAO; PHND; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH

Improving nutrition in Andhra Pradesh: Insights from the current status of outcomes, determinants and interventions in 2016

The purpose of this Policy Note is to examine the current status of undernutrition in Andhra Pradesh and to document geographic variability in the major determinants of nutrition and the coverage of key nutrition and health interventions. In doing this analysis, we aim to highlight key areas of action to improve nutrition in Andhra Pradesh.Non-PRIFPRI1; POSHAN; F Strengthening institutions and governance; CRP4SAO; PHND; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH