Ancestry Specific variation in neuropsychological disorders among the South Asian population

The enormous genetic diversity in South Asia resulting from a long and complex admixture history resulted in the emergence of variation in various traits and variations in disease susceptibility. Neuropsychological disorders are one such example that shows variation at the population level. In this study, we aimed at understanding the variation in neuropsychological disorders at the population level among South Asian populations by curating, comparing and contrasting single nucleotide polymorphisms (SNPs), known to be associated with the same. Whole-genome data comprising of 1662 South Asians, belonging to 241 distinct populations were obtained from the database of Dr. David Reich, Harvard Medical School, USA. Principal Component Analysis (PCA) revealed that the Ancestral Tibeto Burman (ATB) genomes form a distinct and distinguishable cluster for the SNPs known to be associated with neuropsychological disorders. Identical By Descent (IBD) analysis showed that out of the top seven populations in terms of IBD sharing, six are from Southern India indicating that these populations may have undergone a recent selective sweep for these SNPs. Further, out of the top ten genomes, according to the number of genomes fixed for the minor alleles, seven were from Southern India. Furthermore, several indigenous populations from South India depicted high F values (>0.25) for SNPs associated with neuropsychological disorders, indicating higher susceptibility for neuropsychological disorders among these South Indian populations. Interestingly, we found that most of the SNPs, fixed for the alternative alleles, were also found to be fixed among the ancient genomes from Indus Valley Civilization (IVC), indicating that these SNPs likely got transmitted to various modern-day South Indian populations from IVC

On the warm pool dynamics in the southeastern Arabian Sea during April - May 2005 based on the satellite remote sensing and ARGO float data

Observational data from the Arabian Sea Monsoon Experiment (ARMEX-Phase IIA) in the southeastern Arabian Sea (SEAS) showed intense warming with the SST up to 31.5°C during April-May 2005. Analysis of 5-day repeat cycles of temperature and salinity profiles from an ARGO float (ID No. 2900345) in a 3°x1° box closer to ARMEX-II buoy (8.3°N, 72.68°E) in the SEAS during January-September 2005 revealed evolution of warm pool (SST>28°C) in spring 2005. The Argo data derived D20 (depth of 20°C isotherm) showed the influence of remote forcing during January-May, and local wind forcing during southwest monsoon. Low salinity waters (<34.0) occupied the top 30 m during January-February followed by temperature inversions (up to 0.5°C) in the 30-60 m depth range. From the peak spring warming, the SST dropped gradually by 3.5°C by end-July with the advent of southwest monsoon followed by a decrease in net heat gain upto 100 W/m^2. The merged weekly products of sea surface height anomalies and the NLOM simulated surface currents showed complex surface circulation consisting of seasonal Lakshadweep High/Low in winter/summer. The examined oceanic and atmospheric variables showed an intraseasonal variability with 41 to 63 day period, coinciding with the Madden-Julian Oscillatio

Normal or Arthritic: Is 25-hydroxy Vitamin D status significant?

Background: Vitamin D is required for proper skeletal development and function. However, the status of vitamin D in healthy subjects and those suffering from arthritis in Nepal is largely unknown. Objective: This study measured vitamin D level in healthy and arthritic individuals of Western Nepal. Methods: Vitamin D level in healthy and arthritic subjects were measured by using LIASION 25-hydroxy Vitamin D assay, a direct competitive chemiluminescence immunoassay (CLIA). Results: Our result suggested that most of the subjects, irrespective of age and disease condition, have subnormal/normal level of vitamin D (≥16ng/mL). Also, the data suggested that serum vitamin D level is significantly higher in males than in females. Moreover, the vitamin D level is higher in healthy individuals when compared with those suffering from arthritis. However, vitamin D level in normal subjects and arthritic patients could not be correlated. Conclusion: Vitamin D level is higher in normal subjects compared to arthritic individuals. However, the level could not be correlated suggesting need of a pilot study to determine vitamin D level and its association with arthritis in Nepalese. Journal of Gandaki Medical College Vol. 10, No. 1, 2017, Page: 21-2

Missing Clinical Information in NHS hospital outpatient clinics: prevalence, causes and effects on patient care

In Britain over 39,000 reports were received by the National Patient Safety Agency relating to failures in documentation in 2007 and the UK Health Services Journal estimated in 2008 that over a million hospital outpatient visits each year might take place without the full record available. Despite these high numbers, the impact of missing clinical information has not been investigated for hospital outpatients in the UK.Studies in primary care in the USA have found 13.6% of patient consultations have missing clinical information, with this adversely affecting care in about half of cases, and in Australia 1.8% of medical errors were found to be due to the unavailability of clinical information.Our objectives were to assess the frequency, nature and potential impact on patient care of missing clinical information in NHS hospital outpatients and to assess the principal causes. This is the first study to present such figures for the UK and the first to look at how clinicians respond, including the associated impact on patient care

Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

Molecular assays for antimalarial drug resistance surveillance: A target product profile.

Antimalarial drug resistance is a major constraint for malaria control and elimination efforts. Artemisinin-based combination therapy is now the mainstay for malaria treatment. However, delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong Sub region and may emerge or spread to other malaria endemic regions. This spread is of great concern for malaria control programmes, as no alternatives to artemisinin-based combination therapies are expected to be available in the near future. There is a need to strengthen surveillance systems for early detection and response to the antimalarial drug resistance threat. Current surveillance is mainly done through therapeutic efficacy studies; however these studies are complex and both time- and resource-intensive. For multiple common antimalarials, parasite drug resistance has been correlated with specific genetic mutations, and the molecular markers associated with antimalarial drug resistance offer a simple and powerful tool to monitor the emergence and spread of resistant parasites. Different techniques to analyse molecular markers associated with antimalarial drug resistance are available, each with advantages and disadvantages. However, procedures are not adequately harmonized to facilitate comparisons between sites. Here we describe the target product profiles for tests to analyse molecular markers associated with antimalarial drug resistance, discuss how use of current techniques can be standardised, and identify the requirements for an ideal product that would allow malaria endemic countries to provide useful spatial and temporal information on the spread of resistance

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase

<p>Abstract</p> <p>Background</p> <p>A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens.</p> <p>Findings</p> <p>Oxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes.</p> <p>Conclusions</p> <p>By compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.</p

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

The article reviews agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury