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 Methods: Published and unpublished studies and the grey literature published on women and suicide related to Nepal between 2000 and 2014 were searched and included in this review.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

Investigation of MRSA transmission between pigs and the environment following intra-nasal inoculation

Meticillin-resistant Staphylococcus aureus (MRSA) ST398 has not been detected in pigs in Ireland. However, other strains of MRSA, including MRSA t002, have been isolated from animals and humans in Ireland. The aim of this study was to determine if nasal colonization of pigs with a non-ST398 strain of MRSA could be reproduced using intra-nasal inoculation and to investigate subsequent transmission of this strain. Six pigs were inoculated intra-nasally with 2 x 109cfu MRSA t002. Six days post-inoculation these pigs were washed and moved to a clean house with 15 unexposed pigs (In-contact group). Another 15 unexposed pigs were added to the vacated house (Environment group)

U-Pb zircon SHRIMP evidences of Cambrian volcanism in the Schistose Domain within the Galicia-Tras-os-Montes Zone (Variscan Orogen, NW Iberian Peninsula)

SHRIMP U–Pb zircon analyses have shown the complexity of dating volcanic rocks due to the presence of inner cores within zircon crystals. Using the cathodoluminescence studies assisting ion microprobe analyses allow us to conclude that: the two low-grade metavolcanic samples from the Schistose Domain of the Galicia-Trás-os-Montes Zone in the northeast limb of the Verín-Bragança synform (NW Spain and NE Portugal) yield ages of 488.7 ± 3.7Ma and 499.8 ± 3.7Ma (lowermost Ordovician-Upper Cambrian). The Schistose Domain had been traditionally considered as a parautochthonous tectonic unit, i.e. as the stratigraphic continuation of the autochthonous underlying rocks, only locally or moderately detached from them as a result of strong dragging forces from large allochthonous units above it. Current interpretation of the Schistose Domain suggests that this domain formed the outboard edge of the Iberian terrane. Important Arenig, felsic magmatism with similar geochemical signature to the volcanic bodies in the Schistose Domain of the Galicia-Trás-os-Montes Zone (GTMSD) series is present also in the adjacent Ollo de Sapo Domain of the Central Iberian Zone. This contemporary nature of magmatic events provides an additional argument to support the “Iberian” affinity of the Schistose Domain of the Galicia-Trás-osMontes Zone. However, the Cambro–Ordovician facies are very different in the Schistose Domain with respect to the autochthonous unit, the Central–Iberian Zone, suggesting that the Schistose Domain must be considered as a major allochthonous unit with a displacement of over several tens of kilometers

Downregulation of Key Early Events in the Mobilization of Antigen-bearing Dendritic Cells by Leukocyte Immunoglobulin-like Receptor B4 in a Mouse Model of Allergic Pulmonary Inflammation

Leukocyte Immunoglobulin-like Receptor B4 (LILRB4) null mice have an exacerbated T helper cell type 2 (Th2) immune response and pulmonary inflammation compared with Lilrb4+/+ animals when sensitized intranasally with ovalbumin (OVA) and low-dose lipopolysaccharide (LPS) followed by challenge with OVA. Moreover, OVA-challenged Lilrb4−/− mice exhibit greater migration of antigen (Ag)-bearing dendritic cells (DCs) to lymph nodes and accumulation of interleukin 4- and interleukin 5-producing lymph node lymphocytes. The main objective of this study was to determine how the absence of LILRB4 leads to a greater number of DCs in the lymph nodes of Ag-challenged mice and increased lung Th2 inflammation. Mice were sensitized intranasally with PBS alone or containing OVA and LPS; additional cohorts were subsequently challenged with OVA. Expression of chemokine (C-C motif) ligand 21 (CCL21) in the lung was assessed immunohistologically. OVA ingestion and expression of LILRB4 and chemokine (C-C motif) receptor 7 (CCR7) were quantified by flow cytometry. Inhalation of OVA and LPS induced upregulation of LILRB4 selectively on lung Ag-bearing DCs. After sensitization and challenge, the lung lymphatic vessels of Lilrb4−/− mice expressed more CCL21, a chemokine that directs the migration of DCs from peripheral tissue to draining lymph nodes, compared with Lilrb4+/+ mice. In addition, lung DCs of challenged Lilrb4−/− mice expressed more CCR7, the CCL21 receptor. The lungs of challenged Lilrb4−/− mice also contained significantly greater numbers of CD4+ cells expressing interleukin-4 or interleukin-5, consistent with the greater number of Ag-bearing DCs and Th2 cells in lymph nodes and the attendant exacerbated Th2 lung pathology. Our data establish a new mechanism by which LILRB4 can downregulate the development of pathologic allergic inflammation: reduced upregulation of key molecules needed for DC migration leading to decreases in Th2 cells in lymph nodes and their target tissue

Myosin-X functions in polarized epithelial cells

Myosin-X, an unconventional myosin that has been studied primarily in fibroblast-like cells, has been shown to have important functions in polarized epithelial cell junction formation, regulation of paracellular permeability, and epithelial morphogenesis.Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein–Myo10 localizes to lateral membrane cell–cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis

The Varus Knee Reveals Differential Expression Patterns of miRNAs in Spared vs. Non-spared Compartments

Introduction MicroRNAs (miRNAs) function by repressing cellular protein levels to provide a sophisticated level of gene regulation that coordinates a broad spectrum of biological processes. MiRNA inhibition of mRNA translation has emerged as an important regulator of chondrogenic and osteogenic development, osteoblast, osteoclast and chondrocyte cell growth and differentiation, and tissue homeostasis in the adult skeleton. MiRNAs control many layers of regulation in adult tissues connected to both normal biological and pathologic cellular activities. The study of miRNAs in skeletal disorders is in its infancy. Osteoarthritis (OA) is a disease that progresses from degeneration of the articular cartilage to remodeling of the underlying subchondral bone over many years. While miRNAs have been identified with the inflammatory pathogenesis of rheumatoid arthritis (RA), only a few studies have been performed on OA tissue (1,2) . Here we performed a systematic analysis of the articular cartilage from varus OA knee replacements, comparing multiple tissue samples from the lateral (spared) and medial (diseased) compartments. Before proceeding to a miRNA profiling, each sample was analyzed for expression of a small set of miRNAs that have been reported in association with RA, OA and cartilage formation. These preliminary findings have identified a spectrum of changes in surface cartilage between control and diseased tissue. Methods Human tissues: 6 individual articular cartilage samples were harvested from a total of 5 osteoarthritic varus human knees. Cartilage samples were exempt from IRB review as they are discarded materials. Samples were removed with a biopsy punch and were approximately 6 x 2mm (diameter x thickness). Cartilage specimens were harvested from the more normal-appearing lateral (‘spared’) compartments and from the more OA-affected, medial compartments of the knees. This sampling technique allows direct comparison of more significantly OA-affected cartilage samples with those of lower OA grade from the same set of individuals. Knee ages ranged from 53-74 years old and averaged 65 years old. RNA and miRNA Isolation: Each osteochondral specimen was placed in RNA Later (Sigma) immediately following surgical removal, in order to preserve the integrity of the total RNA. Specimens were transported to the lab where individual samples were removed carefully with RNase-treated tools and were transferred intofresh RNA Later solution and incubated overnight at 4C to allow penetration and maximal inhibition of RNase activity. Samples were then removed from RNA Later, blotted briefly and frozen in liquid N2, and then pulverized using a Bessman tissue pulverizer (Fisher). The pulverized samples were immediately placed into Trizol (InVitrogen) and homogenized using a polytron device. Total RNA was isolated to include small RNAs of \u3e17 nucleotides, according to the manufacturer’s protocol (InVitrogen). Purified RNA was obtained using precipitated total RNAs filtered through glass columns according to the manufacturer’s protocol (Zymo Research). RNAs were reverse-transcribed into DNA using 900ng of each purified RNA sample using the TaqMan microRNA Reverse Transcription Kit (Applied Biosystems). TaqMan qPCR analysis for small RNAs was performed using the following human primer-probe sets from Applied Biosystems: hsa-miRs-: 9, 22, 27a, 29a and 34a. Human U6 was used to normalize all qPCR data and data was plotted as normalized relative values. Normalized relative values were averaged for each of the complement of medial vs. lateral samples. Results MiRs were found to be either up- or down-regulated in a manner that suggests a mechanism of de-repression of pro-inflammatory cytokine signaling and repression of pro-inflammatory events in medial vs. lateral varus knee OA cartilage samples, respectively. MiRs 9, 27a, and 29a were found to up-regulated in lateral varus knee cartilage samples vs. medial varus knee cartilage samples (Fig.1. A,C,E,F). Conversely, miRs 22 and 34a were found to upregulated in medial vs. lateral cartilage samples (Fig1, B, D). Discussion The functional characterization of global gene expression patterns through miRNAs in OA is lacking. Particularly, the roles of miRs in OA disease development, as biomarkers, and in disease outcomes are at question. A few large-scale microarray approaches have previously identified expression signatures of potential OA-involved miRNAs (2). By comparing cartilage samples that derive from more advanced (medial) vs. less advanced (lateral) OA stages in varus human knees, we seek to combine miRNA expression analysis with clinicopathologic features. MiRs -9, -22 and -34a are known to be involved in regulating pro-inflammatory events in OA. Higher levels of miRs, -9, -27a & -140 in less-affected lateral compartment cartilage are consistent with previous reports of reduced TNFa, MMP-13 & ADAMTS-5 expression events, respectively (Fig.1, F, E & A) (3,4,5). MiRs -22 and -34a have been shown to be associated with promoting tissue catabolism by their presence and are here shown to be increased in more affected medial compartment cartilage (Fig.1, B, D) (4). In addition, miR-34a deficiency has been previously shown to inhibit chondrocyte apoptosis, consistent with the lower expression level found in lateral cartilage (Fig.1, D) (6). MiR-29a was found in a previous microarray analysis to be the highest-fold down-regulated miRNA in OA vs. normal cartilage, consistent with our finding of under-expression in medial cartilage samples (Fig.1, C) (1). The goal of these studies is to begin to understand how miRNAs can both contribute to and protect against OA. Here we show that the comparison of cartilage-derived miRNAs in medial and lateral compartment pairs from the same knee may facilitate validation of candidate OA miRNAs. Significance The aims of this project are to provide an internally-controlled platform of study for the miRNAs of OA using the natural disease differences inherent in spared vs. non-spared cartilage compartments from a varus OA knee. Such efforts may provide an alternative methodology when compared to the significant barrier of obtaining age-matched, non-OA control knee cartilage. References 1.) Iliopoulus D. PLoS One. 2008;3(11):e3740. Epub 2008 Nov 17. 2.) Goldring MB. Curr Opin Rheumatol. 2011 Jul 22. [Epub]. 3.) Yu C. J Int Med Res. 2011;39(1):1-9. 4.) Alcaraz MJ. Biochem Pharmacol. 2010 Jul 1;80(1):13-21. 5.) Miyaki S. Genes Dev. 2010 Jun 1;24(11):1173-85. 6.) Abouheif MM. Rheumatology. 2010 Nov;49(11):2054-60

Separation processes during binary monotectic alloy production

Observation of microgravity solidification processes indicates that outside of sedimentation, at least two other important effects can separate the phases: critical-point wetting and spreading; and thermal migration of second-phase droplets due to interfacial tension gradients. It is difficult to study these surface tension effects while in a unit gravity field. In order to investigate the processes occurring over a temperature range, i.e., between a consolute point and the monotectic temperature, it is necessary to use a low-gravity environment. The MSFC drop tube (and tower), the ballistic trajectory KC-135 airplane, and the Space Shuttle are ideal facilities to aid formation and testing of hypotheses. Much of the early work in this area focuses on transparent materials so that process dynamics may be studied by optical techniques such as photography for viewing macro-processes; holography for studying diffusional growth; spinodal decomposition and coalescence; ellipsometry for surface wetting and spreading effects; and interferometry and spectroscopy for small-scale spatial resolution of concentration profiles

Mental health issues in pregnant women in Nepal

Mental health of pregnant women and new mothers is a growing area of concern in both low- and high-income countries. This editorial highlights some of the key mental issues faced by women in rural Nepal and outlines an intervention based on training community health care workers by experienced UK volunteers