Why are so many Nepali women killing themselves? A review of key issues

Background: For decades the maternal mortality in Nepal was the lead cause of death among women, with great improvements in the maternal mortality ratio in the twentieth century the second most common cause has become more prominent. Suicide is now one of the leading causes of death for women of a reproductive age in Nepal. This scoping review brings together the key available literature to identify the causes of suicide among women in Nepal. Methods: Published and unpublished studies and the grey literature published on women and suicide related to Nepal between 2000 and 2014 were searched and included in this review. Results: This review suggested a number of explanations for the high rate of suicide among women including: partner violence, alcoholism and polygamy, the culture of silence, early age marriage and prolonged child bearing and dependency on men for financial security. Conclusion: This paper highlights some challenges and suggests ways forward in the improvement of mental health in Nepal

Crowd disagreement about medical images is informative

Classifiers for medical image analysis are often trained with a single consensus label, based on combining labels given by experts or crowds. However, disagreement between annotators may be informative, and thus removing it may not be the best strategy. As a proof of concept, we predict whether a skin lesion from the ISIC 2017 dataset is a melanoma or not, based on crowd annotations of visual characteristics of that lesion. We compare using the mean annotations, illustrating consensus, to standard deviations and other distribution moments, illustrating disagreement. We show that the mean annotations perform best, but that the disagreement measures are still informative. We also make the crowd annotations used in this paper available at \url{https://figshare.com/s/5cbbce14647b66286544}.Comment: Accepted for publication at MICCAI LABELS 201

Factors affecting the uptake of institutional delivery, antenatal and postnatal care in Nawalparasi district, Nepal

© 2019, Kathmandu University. All rights reserved. Background Maternal deaths and complications are highly preventable with good antenatal, postnatal and skilled care during childbirth. Inadequate information on the factors affecting these services could be barrier to a reduction of maternal deaths in low-income countries. Objective To assess the uptake of antenatal, postnatal and skilled care during childbirth. Method A cross-sectional study was conducted in eight villages of Nawalparasi district in southern Nepal. A total of 447 women who had given birth within the preceding 24 months were recruited using multistage random sampling. Data were collected using a pre-tested semi-structured questionnaire. Chi-square tests were used to assess association between variables. Result Over 70% of women had gone for at least four antenatal care check-ups while only 14.3% had at least three postnatal check-ups in their last pregnancies. The proportion of institution delivery was 54%. Women’s literacy was associated with the uptake of antenatal services (p=<0.001), postnatal care (p=0.04) and institutional delivery (p=<0.001). Knowledge of antenatal (p=<0.001) and postnatal care was also associated with uptake of respective services (p=<0.001). Conclusion The uptake and knowledge of antenatal care was much better than of postnatal care. Home delivery rates were still very high. A scaling-up of education and awareness-raising interventions in this community could help improve the uptake of maternal health services

microRNA199a based post-transcriptional detargeting of gene vectors for Hepatocellular Carcinoma

A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or other major organs. miRNA-based negative detargeting has gained considerable attention in recent times due to its effectiveness and the ease with which it can be adapted into current gene delivery vectors. In this study, we provide a proof-of-concept using miRNA199a as a negative targeting agent. We introduced vectors harboring reporters with miRNA199a binding sites in cells expressing high endogenous levels of miRNA199a and compared the reporter expression in HCC cells with low endogenous miRNA199a. We observed that the expression of reporters with miRNA199a binding sites is significantly inhibited in miRNA199a-positive cells, whereas minimal effect was observed in miRNA199a-negative HCC cells. In addition, we created a post-transcriptionally regulated suicide gene therapeutic system based on cytosine deaminase (CD)/5-fluorocytosine (5-FC) exploiting miRNA199a binding sites and observed significantly lower cell death for miRNA199a-positive cells. Furthermore, we observed a decrease in the levels of miRNA199 in 3D tumorspheres of miRNA199a-positive Hepa1-6 cells and a reduction in the inhibition of reporter expression after transfection in these 3D models when compared with 2D Hepa1-6 cells. In summary, we provide evidence of miRNA199a-based post-transcriptional detargeting with relevance to HCC gene therapy

miRNA122a regulation of gene therapy vectors targeting hepatocellular cancer stem cells

In this study, we report a miRNA122a based targeted gene therapy for hepatocellular cancer stem cells (CSCs). First, we assessed the levels of miRNA122a in normal human hepatocytes, a panel of hepatocellular carcinoma (HCC) cell lines and hepatocellular CSCs observing its significant downregulation in HCC and CSCs. The miRNA122a binding site was then incorporated at the 3'-UTR of reporter genes gaussia luciferase (GLuc) and eGFP which resulted in significant hepatocyte detargeting. Using this strategy for the delivery of gene directed enzyme prodrug therapy (GDEPT) utilizing the cytosine deaminase/5-fluorocytosine (CD/5-FC) system, we showed significant killing in cells with low or no miRNA122a while those cells, such as hepatocytes with high miRNA122a were largely spared. Next, we showed that CSC enriched tumorspheres exhibit a significant downregulation of miRNA122a expression providing a rational to exploit its binding site for targeted gene delivery. Using plasmids harboring reporters GLuc and eGFP with or without miR122a binding sites, we showed high reporter expression in the CSCs and little reported expression in the non-enriched cultures. Finally, we demonstrate the efficacy of miRNA122a based post-transcriptionally targeted GDEPT for hepatocellular CSCs

A comprehensive and version-controlled database of glacial lake outburst floods in High Mountain Asia

Glacial lake outburst floods (GLOFs) have been intensely investigated in High Mountain Asia (HMA) in recent years and are the most well-known hazard associated with the cryosphere. As glaciers recede and surrounding slopes become increasingly unstable, such events are expected to increase, although current evidence for an increase in events is ambiguous. Many studies have investigated individual events, and while several regional inventories exist, they either do not cover all types of GLOF or are geographically constrained. Further, downstream impacts are rarely discussed. Previous inventories have relied on academic sources and have not been combined with existing inventories of glaciers and lakes. In this study, we present the first comprehensive inventory of GLOFs in HMA, including details on the time of their occurrence, processes of lake formation and drainage involved, and downstream impacts. We document 697 individual GLOFs that occurred between 1833 and 2022. Of these, 23 % were recurring events from just three ephemeral ice-dammed lakes. In combination, the documented events resulted in 6906 fatalities of which 906 can be attributed to 24 individual GLOF events, which is 3 times higher than a previous assessment for the region. The integration of previous inventories of glaciers and lakes within this database will inform future assessments of potential drivers of GLOFs, allowing more robust projections to be developed. The database and future, updated versions are traceable and version-controlled and can be directly incorporated into further analysis. The database is available at https://doi.org/10.5281/zenodo.7271187 (Steiner and Shrestha, 2023), while the code including a development version is available on GitHub.</p

Double burden of malnutrition in Nepal: A trend analysis of protein-energy malnutrition and High Body Mass Index using the data from Global Burden of Disease 2010–2019

Background The co-existence of undernutrition and overnutrition is a global public health threat. We aim to report the burden of both nutritional deficiency (Protein-Energy Malnutrition) and overweight (high Body Mass Index) in Nepal over a decade (2010–2019) and observe the changes through trend charts. Methods We did a secondary data analysis using the Institute for Health Metrics and Evaluation (IHME)’s Global Burden of Disease (GBD) database to download age-standardized data on Protein Energy Malnutrition (PEM) and high Body Mass Index (BMI). We presented the trend of death, Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years Lost due to Disability (YLD) of PEM and high BMI in Nepal from 2010 to 2019 and also compared data for 2019 among South Asian countries. Results Between 2010 and 2019, in Nepal, the Disability Adjusted Life Years (DALYs) due to PEM were declining while high BMI was in increasing trend. Sex-specific trends revealed that females had higher DALYs for PEM than males. In contrast, males had higher DALYs for high BMI than females. In 2019, Nepal had the highest death rate for PEM (5.22 per 100,000 populations) than any other South Asian country. The burden of PEM in terms of DALY was higher in under-five children (912 per 100,000 populations) and elderly above 80 years old (808.9 per 100,000 populations), while the population aged 65–69 years had the highest burden of high BMI (5893 per 100,000 populations). In the last decade, the DALYs for risk factors contributing to PEM such as child growth failure (stunting and wasting), unsafe water, sanitation and handwashing, and sub-optimal breastfeeding have declined in Nepal. On the contrary, the DALYs for risk factors contributing to high BMI, such as a diet high in sugar-sweetened beverages, a diet high in trans fatty acid, and low physical activity, have increased. This could be a possible explanation for the increasing trend of high BMI and decreasing trend of PEM. Conclusion Rapidly growing prevalence of high BMI and the persistent existence of undernutrition indicate the double burden of malnutrition in Nepal. Public health initiatives should be planned to address this problem

Widespread hybridization in the introduced hog deer population of Victoria, Australia, and its implications for conservation

In Australia, many species have been introduced that have since undergone drastic declines in their native range. One species of note is the hog deer (Axis porcinus) which was introduced in the 1860s to Victoria, Australia, and has since become endangered in its native range throughout South-East Asia. There is increased interest in using non-native populations as a source for genetic rescue; however, considerations need to be made of the genetic suitability of the non-native population. Three mitochondrial markers and two nuclear markers were sequenced to assess the genetic variation of the Victorian population of hog deer, which identified that the Victorian population has hybrid origins with the closely related chital (Axis axis), a species that is no longer present in the wild in Victoria. In addition, the mitochondrial D-loop region within the Victorian hog deer is monomorphic, demonstrating that mitochondrial genetic diversity is very low within this population. This study is the first to report of long-term persistence of hog deer and chital hybrids in a wild setting, and the continual survival of this population suggests that hybrids of these two species are fertile. Despite the newly discovered hybrid status in Victorian hog deer, this population may still be beneficial for future translocations within the native range. However, more in-depth analysis of genetic diversity within the Victorian hog deer population and investigation of hybridization rates within the native range are necessary before translocations are attempted