A Survey of Obstetric Healthcare Utilization in the Rural Western Indian Himalayas

Objectives To determine the socio-economic factors affecting access to antepartum, intrapartum, and postpartum healthcare in the rural Western Indian Himalayas over the past 20 years. Methods Face-to-face surveys were conducted with 197 women in Chamoli District, Uttarakhand from October 2011 to May 2012. Participants who gave birth within the past 20 years were included in the final analysis (n = 158). Stratified odds ratios and analysis of variance were calculated. Results Among women who delivered in the prior 7 years, there was a nine-fold increase (95 % CI 4–20.8) in institutionalized births compared to women who delivered 8–20 years before the study. Among women who delivered 7 years prior to the study, low income increased the risk of home delivery (OR 3.07, 95 % CI 1.15–8.54). Low caste (OR 2.79, 95 % CI 1.04–7.72) and low level of education (OR 3.93 95 % CI 1.41–11.81) decreased the use of antepartum medications (vitamins and vaccines). Remote location among all participants was a risk factor for not seeking care for obstetric morbidities (OR 0.44 95 % CI 0.2–0.95). Conclusions The incidence of institutionalized delivery has increased over the past decade in rural Uttarakhand. Income, caste, education, and remote location correlated with poor access to antepartum and intrapartum healthcare. These correlations have increased in statistical significance over the past 20 years, except for location. This indicates that the Western Himalayas face similar challenges to obstetric service utilization as the north Indian plains and that several of these inequalities in healthcare access have become more pronounced in recent years.     

Role of altered immune cells in liver diseases: a review

Immune cells play an important role in controlling liver tumorigenesis, viral hepatitis, liver fibrosis and contribute to pathogenesis of liver inflammation and injury. Accumulating evidence suggests the effectiveness of natural killer (NK) cells and Kupffer cells (KCs) against viral hepatitis, hepatocellular damage, liver fibrosis, and carcinogenesis. Activation of natural killer cells provides a novel therapeutic strategy to cure liver related diseases. This review discusses the emerging roles of immune cells in liver disorders and it will provide baseline data to scientists to design better therapies for treatment.     

New aromatic esters from Galinsoga parviflora

Galinosoates A-C (1-3), new aromatic esters, have been isolated from the n-hexane soluble fraction of Galinsoga parviflora. Their structures were assigned from the spectral data including IR, HR-EI-MS, 1D and 2D NMR.     

Menstrual effluent in endometriosis shows no difference in volume, VEGF-A, MMP2 and MMP9 or sFLT

Since retrograde menstruation is considered a key event in the aetiology of endometriosis, this study sought to determine whether the menstrual effluent of women with this condition is different from that of those with a normal pelvis. As the amount of blood lost during menstruation is thought to be higher in this group, measured objective menstrual blood loss (MBL) was measured. In addition, factors enhancing both ectopic implantation of endometrium and its subsequent growth (by establishing a neo-vasculature) were chosen for study. Our hypothesis was that they are increased in the menstrual effluent of women with endometriosis. The study showed that at the time of menstruation, there is no difference in MBL or in the volume of menstrual effluent between women with endometriosis and those with a normal pelvis at laparoscopy. In addition, vascular endothelial growth factor-A (VEGF-A) message and protein, soluble truncated receptor sVEGF-R1 (sFLT), matrix metalloproteinase (MMP) 2 and MMP9 activities were also shown to be similar between the two groups. It is concluded that the enhanced expression of VEGF-A and MMP in the peritoneal fluid and ectopic lesions of endometriotic patients may be a secondary event, resulting from an innate difference in peritoneal and systemic factors rather than in the endometrium, causing an abnormal peritoneal response to menstrual debris and facilitating its ectopic implantation.     

Monoclonal antibody classification based on epitope-binding using differential antigen disruption

Currently, classifying a population of specific antigen-reactive monoclonal antibodies (mAbs) according to their epitope-binding properties has been limited to competition assays. Such assays are time consuming, labor intensive and restricted to the number of mAbs in the experiment. To overcome this problem, a differential antigen disruption-based antibody profiling procedure was developed. This procedure rapidly classifies specific antigen-reactive mAbs into epitope-related groups by measuring the binding signal of the antibodies to a set of structurally disrupted antigens and then clustering the antibodies according to the similarity of their binding profiles. The clustering results generated by differential antigen disruption showed a significant concordance with those generated by competition experiments. Therefore, differential antigen disruption method opens an opportunity to assess the entire population of antigen-reactive mAbs according to their epitope-binding properties. In doing so, a set of representative antibodies can be drawn to describe the epitope complexity for systematically exploring their functions.     

The changing epidemiology pattern and frequency distribution of hepatitis C virus in Pakistan

Information regarding the changing pattern in hepatitis C virus (HCV) genotypes/subtypes and resulting disease outcome is not well known. The specific objective of this study was to find out the frequency distribution of HCV genotypes and changing pattern of various HCV genotypes overtime in well-characterized Pakistani HCV isolates. The genotype distribution of HCV from all the four provinces of Pakistan was tracked for a period of 10 years (2000–2009) on total 20,552 consecutive anti-HCV and HCV RNA positive patients sample using type-specific genotyping assay. Of these, 16,891 (82.2%) samples were successfully genotyped. Of these 11,189 (54.4%) were males and 9363 (45.55%) were females. Of the successfully genotyped samples, 12,537 (74.2%) were with 3a, 1834 (10.9%) with 3b, 50 (0.24%) with 3c, 678 (3.3%) with 1a, 170 (0.83%) with 1b, 49 (0.24%) with 1c, 431 (2.1%) with 2a, 48 (0.23%) with 2b, 3 (0.01%) with 2c, 13 (0.06%) with 5a, 12 (0.06%) with 6a, 101 (0.49%) with 4, and 965 (4.7%) were with mixed-genotype infection. A changing pattern of HCV genotypes prevalence was observed in Pakistan overtime, with an increase in the relative proportion of genotype 3a and mixed genotypes and a decrease of genotypes 3b, 2b, 4, 5a and 2a. This changed HCV genotype pattern might have direct impact on HCV disease outcome and new therapeutic strategies may be needed.     

Role of MyD88-adaptor-like gene polymorphism rs8177374 in modulation of malaria severity in the Pakistani population

Introduction

The present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of Plasmodium vivax and Plasmodium falciparum.

Aflibercept exhibits VEGF binding stoichiometry distinct from bevacizumab and does not support formation of immune-like complexes

Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF₁₆₅, resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fcγ receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fcγ receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF₁₆₅.