Human rights violations among sexual and gender minorities in Kathmandu, Nepal: a qualitative investigation

BACKGROUND: Nepal has experienced sporadic reports of human rights violations among sexual and gender minorities. Our objective was to identify a range of human rights that are enshrined in international law and/or are commonly reported by sexual and gender minority participants in Kathmandu, to be nonprotected or violated. METHODS: In September 2009 three focus group discussions were conducted by trained interviewers among a convenience sample of sexual and gender minority participants in Kathmandu Nepal. The modified Delphi technique was utilized to elicit and rank participant-generated definitions of human rights and their subsequent violations. Data was analyzed independently and cross checked by another investigator. RESULTS: Participants (n = 29) reported experiencing a range of human rights violations at home, work, educational, health care settings and in public places. Lack of adequate legal protection, physical and mental abuse and torture were commonly reported. Access to adequate legal protection and improvements in the family and healthcare environment were ranked as the most important priority areas. CONCLUSIONS: Sexual and gender minorities in Nepal experienced a range of human rights violations. Future efforts should enroll a larger and more systematic sample of participants to determine frequency, timing, and/or intensity of exposure to rights violations, and estimate the population-based impact of these rights violations on specific health outcome

Engineering Antibodies to Enhance Activity and Increase Half-life

Background: HIV/AIDS remains one of the most serious current threats to global public health. Although anti-HIV drugs have been effective among the wealthiest populations, a vaccine and/or new methods to prevent infections are needed lo control HIV globally. Strategies to combat HIV-1 require structural knowledge of how antibodies recognize HIV envelope proteins and how the immune system eliminates viruses. Until recently, only a small number of broadly neutralizing antibodies against HIV-1 had been characterized, and the immunological basis for their breadth and potency remains poorly understood. However. it was recently demonstrated that antibodies could be engineered to greatly enhance their breadth and potency (Diskin et al., Science 2011). Unfortunately, this and other engineering efforts have resulted in a decrease in antibody half-life in mouse and non-human primate models. This decrease in half-life correlates with an increase in reactivity to a variety of antigens, termed polyreactivity. Methods: In order to make better targets for passive delivery therapies, we are working to increase the half-life of antibodies while maintaining their breadth and potency using a variety of computational and structured-based techniques. One technique involves reducing the spatial aggregation propensity, in which an algorithm finds dynamically exposed hydrophobic patches on the surlace of proteins (Chemansetty et al., PNAS 2009). To this end, we have constructed several mutations in regions that have been predicted to have high aggregation propensities, and have tested them for polyreactivity and potency in neutralization assays. Results: Initial results show that these novel reagents have reduced polyreactivily, yet they still maintain their potency in in vitro neutralization assays. Conclusions: We are currently pursuing in vivo experiments in mice to further understand the relationship between antibody potency, polyreactivity, and half-life

Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya.

Multidrug resistant (MDR) Klebsiella pneumoniae is a common cause of nosocomial infections worldwide. Recent years have seen an explosion of resistance to extended-spectrum ?-lactamases (ESBLs) and emergence of carbapenem resistance. Here, we examine 198 invasive K. pneumoniae isolates collected from over a decade in Kilifi County Hospital (KCH) in Kenya. We observe a significant increase in MDR K. pneumoniae isolates, particularly to third generation cephalosporins conferred by ESBLs. Using whole-genome sequences, we describe the population structure and the distribution of antimicrobial resistance genes within it. More than half of the isolates examined in this study were ESBL-positive, encoding CTX-M-15, SHV-2, SHV-12 and SHV-27, and 79% were MDR conferring resistance to at least three antimicrobial classes. Although no isolates in our dataset were found to be resistant to carbapenems we did find a plasmid with the genetic architecture of a known New Delhi metallo-?-lactamase-1 (NDM)-carrying plasmid in 25 isolates. In the absence of carbapenem use in KCH and because of the instability of the NDM-1 gene in the plasmid, the NDM-1 gene has been lost in these isolates. Our data suggests that isolates that encode NDM-1 could be present in the population; should carbapenems be introduced as treatment in public hospitals in Kenya, resistance is likely to ensue rapidly

A Method for Amplicon Deep Sequencing of Drug Resistance Genes in Plasmodium falciparum Clinical Isolates from India.

A major challenge to global malaria control and elimination is early detection and containment of emerging drug resistance. Next-generation sequencing (NGS) methods provide the resolution, scalability, and sensitivity required for high-throughput surveillance of molecular markers of drug resistance. We have developed an amplicon sequencing method on the Ion Torrent PGM platform for targeted resequencing of a panel of six Plasmodium falciparum genes implicated in resistance to first-line antimalarial therapy, including artemisinin combination therapy, chloroquine, and sulfadoxine-pyrimethamine. The protocol was optimized using 12 geographically diverse P. falciparum reference strains and successfully applied to multiplexed sequencing of 16 clinical isolates from India. The sequencing results from the reference strains showed 100% concordance with previously reported drug resistance-associated mutations. Single-nucleotide polymorphisms (SNPs) in clinical isolates revealed a number of known resistance-associated mutations and other nonsynonymous mutations that have not been implicated in drug resistance. SNP positions containing multiple allelic variants were used to identify three clinical samples containing mixed genotypes indicative of multiclonal infections. The amplicon sequencing protocol has been designed for the benchtop Ion Torrent PGM platform and can be operated with minimal bioinformatics infrastructure, making it ideal for use in countries that are endemic for the disease to facilitate routine large-scale surveillance of the emergence of drug resistance and to ensure continued success of the malaria treatment policy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Uterine preservation with Cho suture in localized multifocal atonicity of uterus with failed medical management and uterine tamponade

Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality, and one of the common obstetrical emergencies. Quite commonly, it occurs in patients where PPH is not expected. Management has to be swift and precise according to the steps and the response initiated by the uterine musculature during the management. In our patient, we had a localized multifocal atony of the uterus, at points where the uterine sinuses were bleeding due to atony, and medical management and uterine tamponade failed, with a raised D-dimer level. As the stepwise management failed with uterine devascularisation failing to control PPH, a decision for uterine compression suture (UCS), Cho suture was taken

Histopathological spectrum of non-infectious erythematous, papulo-squamous lesions: at a teritary care institute

Background: Dermatologic disorders are common in many countries, but the spectrum varies greatly. Papulosquamous lesions of the skin are encountered with considerable frequency. There is overlap of both clinical pattern and distribution of papulosquamous skin disorders, which often makes clinical diagnosis difficult, Histopathology is highly specific and sensitive for many lesions and its remains the gold standard for most dermatological diagnosis.Methods: A prospective histopathological study of 50 cases, which was carried out in the department of dermatology and Pathology in L. N. medical college and J. K. hospital research center, over a period of 1 year. A brief history and dermatological examination was carried out, skin biopsies taken were fixed in 10% formalin and subjected for tissue processing. Followed by microscopic examination.Results: In the present study of 50 cases of papulosquamous disorders psoriasis 60% (30 Cases) was the commonest followed by lichen planus 20% (10 cases), 3% (6 cases) each of pityriasis rubra, pilaris, parapsoriasis, Pityriasis rosea, and 4% (02 cases) of seborrheic dermatitis. Commonest age-group 31-40 years was more affected, sex distribution pattern revealed a male preponderence. 30 cases showed compatible clinical as well as histopathological diagnosis.Conclusions: Key histopathological features and clinico-pathological study gives a conclusive diagnosis. The importance of specific histo-morphological diagnosis lies in the distinguishing various lesions and their prognosis

Docosahexaenoic acid supplementation: a need or a commercial hype?

Docosahexaenoic acid (DHA) is an important component of the brain and is essential critical for optimal brain health and function. With revealing of its beneficial effects on cognitive function, neurological, cardiovascular system and anti-inflammatory benefits, DHA has recently gained huge attention. As a result, the market is stocked with products supplemented with DHA claiming various health benefits. This review attempts to elucidate the current findings of DHA supplementation as a pharmacological agent with both preventive and therapeutic value

Pregnancy and Lactation in a 67-Year-Old Elderly Gravida following Donor Oocyte

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum course was uncomplicated, and she was able to successfully breastfeed for six months and resume prepregnancy activity. For comparison, we analyzed deliveries among gravidae \u3e 45 years of age from our institutional obstetrical database (2011-2018). This case represents the eldest gravidae identified in the literature and illustrates the potential for a relatively uncomplicated perinatal course with successful lactation. This case may enable other providers to counsel elderly patients on anticipated outcomes inclusive of ability to breastfeed

Evaluation of antidepressant activity of ondansetron alone and in combination with fluoxetine-an experimental study

Background: Direct antagonism at 5HT3 receptor site may be associated with antidepressant activity as conventional antidepressants also possess affinity for central 5HT3 binding site. So in this study, an effort is made to investigate the antidepressant effect of ondansetron (OND), a selective 5HT3 antagonist, alone and in combination with fluoxetine (FLX).Methods: Acute and chronic models of Forced swimming test (FST), tail suspension test (TST), open field test (OFT) and mice brain serotonin estimation  by UV spectrophotometry were applied for the evaluation of antidepressant activity.Results: In FST and TST (acute and chronic models), ondansetron showed statistically significant antidepressant activity (p<0.05) as compared to control. The combination groups (OND 0.25 mg/kg + FLX 5mg/kg & OND 0.5 mg/kg + FLX 5 mg/kg) showed statistically significant antidepressant activity (p<0.05) as compared to fluoxetine (5 mg/kg) and ondansetron (0.25 mg/kg and 0.5 mg/kg) in FST and TST (acute and chronic models). Open field test in chronic study showed ondansetron (0.25 mg/kg and 0.5 mg/kg) increases number of central squares crossed as compared to control which is statistically significant (p<0.05). The combination group (OND 0.25 mg/kg + FLX 5 mg/kg) showed significantly increased (p<0.05) number of central squares crossed as compared to fluoxetine (5 mg/kg). The combination group (OND 0.5 mg/kg + FLX 5 mg/kg) showed significantly increased (p<0.05) brain serotonin compared to control, ondansetron (0.25 mg/kg and 0.5 mg/kg) and fluoxetine (5 mg/kg).Conclusions: Our study concludes that ondansetron alone and in combination with fluoxetine possesses significant antidepressant activity in animal models of depression