A long-term "memory" of HIF induction in response to chronic mild decreased oxygen after oxygen normalization

Background Endothelial dysfunction (ED) is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF) is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED. Methods Human endothelial and aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood oxygen levels in patients with heart failure, or to C) mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS) were measured both at the protein and mRNA levels. Results It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization. Conclusion These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress

A retrospective comparative study of multiple choice questions versus short answer questions as assessment tool in evaluating the performance of the students in medical pharmacology

Background: The aim was to assess the effectiveness of multiple choice versus short answer questions (SAQs) as assessment tools for evaluating performance of 2nd MBBS students.Methods: The study was observational, retrospective study of written pen and paper type assessment that utilized a sample of 100 2nd year medical students. Study consisted of two parts; part I was multiple-choice questions (MCQs) based on endocrine system where four options were given for a question and the single best answer was to be ticked. MCQ was timed at 20 mins for 30 questions with 1 mark each. There was no negative marking. Part II was SAQ on same system where 16 SAQ were given. SAQ was timed at 60 mins for 30 marks questions. After the test students had to reply on a feedback form.Result: There was a strong correlation between the marks scored in two formats of test and there was no statistical difference between the two set of marks.Conclusion: SAQs are as effective as MCQs in assessing the performance of the students in medical pharmacology

Simulation of IRNSS Navigation Payload Operations for End to End Payload Testing

Fault free operations of space vehicles have always been a challenging task. Every space mission requires stringent qualification process on ground for qualification of the space vehicle for mission operations. This paper deals with the simulation of IRNSS navigation payload operations on ground for end to end payload testing and qualification of the payload for broadcast of IRNSS navigation parameters. IRNSS is an emerging Indian regional navigation satellite system for providing the satellite based navigation service over India and neighboring region. The system is optimally designed for its space and ground segment to provide the best in class navigation service. The space segment comprises of 7 satellites with 4 satellites in geo-synchronous orbit and 3 in geo-stationary orbit. The navigation payload on-board every IRNSS spacecraft comprises of navigation signal generation unit, atomic clocks and ranging subsystems. For every IRNSS spacecraft, a series of tests are carried out during different phases of spacecraft integration and testing. The core elements of IRNSS navigation operations such as IRNSS navigation software, payload test receiver, atomic clocks and telecommand and telemetry subsystem all participate in simulation and end to end testing of navigation payload. This paper describes in detail the simulation of various mission scenarios with respect to navigation payload operations considering different phases of satellite operations, subsystems involved and environment. The simulation has been key to successful operations of IRNSS 1A and IRNSS 1B which are operational in IRNSS space segment. Keywords: IRNSS, Navigation, payload, simulatio

Do health systems delay the treatment of poor children? A qualitative study of child deaths in rural Tanzania.

Child mortality remains one of the major public-health problems in Tanzania. Delays in receiving and accessing adequate care contribute to these high rates. The literature on public health often focuses on the role of mothers in delaying treatment, suggesting that they contact the health system too late and that they prefer to treat their children at home, a perspective often echoed by health workers. Using the three-delay methodology, this study focus on the third phase of the model, exploring the delays experienced in receiving adequate care when mothers with a sick child contact a health-care facility. The overall objective is to analyse specific structural factors embedded in everyday practices at health facilities in a district in Tanzania which cause delays in the treatment of poor children and to discuss possible changes to institutions and social technologies. The study is based on qualitative fieldwork, including in-depth interviews with sixteen mothers who have lost a child, case studies in which patients were followed through the health system, and observations of more than a hundred consultations at all three levels of the health-care system. Data analysis took the form of thematic analysis. Focusing on the third phase of the three-delay model, four main obstacles have been identified: confusions over payment, inadequate referral systems, the inefficient organization of health services and the culture of communication. These impediments strike the poorest segment of the mothers particularly hard. It is argued that these delaying factors function as 'technologies of social exclusion', as they are embedded in the everyday practices of the health facilities in systematic ways. The interviews, case studies and observations show that it is especially families with low social and cultural capital that experience delays after having contacted the health-care system. Reductions of the various types of uncertainty concerning payment, improved referral practices and improved communication between health staff and patients would reduce some of the delays within health facilities, which might feedback positively into the other two phases of delay

PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.

SUMMARY: PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants. AVAILABILITY AND IMPLEMENTATION: PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.This work was supported by the UK Medical Research Council [G0800270; MR/L003120/1], the British Heart Foundation [SP/09/002; RG/13/13/30194; RG/18/13/33946], Pfizer [G73632], the European Research Council [268834], the European Commission Framework Programme 7 [HEALTH-F2-2012-279233], the National Institute for Health Research and Health Data Research UK (*). *The views expressed are those of the authors and not necessarily those of the NHS or the NIHR

Celastrus paniculatus and memantine prevent alcohol dependence and improve decision making in alcohol dependent C57BL6 mice

Background: Alcohol use disorder poses a huge burden with only a handful of approved drugs. AUD is associated with impaired decision-making that leads to compulsive drinking despite negative consequences. A drug that decreases alcohol consumption as well as improves decision-making may thus prove more useful. This study was planned to evaluate the effect of two drugs, Celastrus paniculatus and memantine on alcohol preference and decision impairment in alcohol-dependent mice. Methods: In part 1, the effect of both the study drugs on alcohol consumption was studied using intermittent access model in 70 male C57BL6 mice. In part 2, effect of drugs on decision making was studied using the rodent version of Iowa gambling task. Mice were divided in seven study groups: Group 1-3: Celastrus paniculatus (140, 280, and 560 mg/kg), Group 4: memantine (25 mg/kg), Group 5: vehicle control 1 (Milk), Group 6: vehicle control 2 (normal saline) and Group 7: naltrexone(1mg/kg). Results: Percentage alcohol preference was lower in test groups i.e., Celastrus paniculatus at medium (40.90±15.18%) and high doses (31.79±7.46%) vs. milk (82.74±8.53%; p<0.05); and in memantine group (36.28±10.99%) vs. normal saline (83.27±5.51%; p<0.05). The results were not significantly different to Naltrexone (19.70±6.90%). Percentage preference to disadvantageous arms was also lower in Celastrus paniculatus, at medium (50.52±1.92%) and high doses (48.11±2.43%) compared to milk (54.47±2.73%; p<0.05) and memantine (47.45±1.67%) compared to normal saline (54.00±2.73%; p<0.05), indicating better decision-making ability in the test groups. The findings were comparable to Naltrexone group (45.43±2.52%). Conclusions: These results indicate that Celastrus paniculatus and memantine reduce alcohol consumption and improve decision making in alcohol-dependent mice

Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery

Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8 hours (P = .02), and SAPID 0–8 hours (P < .0001). It also showed faster onset of action (42 minutes) and longer duration of action (6.5 hours). The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety