492 research outputs found

    Challenges and Problems in Transferring an In-House System based Digital Catalogue into Open Source System (KOHA) A case study of Bait ul Hikmah Library, Pakistan

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    Nowadays many Libraries in the process of transforming the manual catalogs into a database in the form of Digital Catalogue. KOHA, because it is an Open source and contains a complete integrated system is the preferable choice of librarians of the developing countries. But there are many challenges and problems occurred and made the task difficult. Presently the Bait AL Hikmah Library of Hamdard University is also in process of converting its in-house based digital catalog and library system and services into KOHA. The paper is a case study of the existing system, there drawbacks and limitations, reasons for choosing KOHA, and finall

    Global variation of COVID-19 mortality rates in the initial phase

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    Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastation in over 200 countries. Italy, Spain, and the United States (US) were most severely affected by the first wave of the pandemic. The reasons why some countries were more strongly affected than others remain unknown. We identified the most-affected and less-affected countries and states and explored environmental, host, and infrastructure risk factors that may explain differences in the SARS-CoV-2 mortality burden. Methods: We identified the top 10 countries/US states with the highest deaths per population until May 2020. For each of these 10 case countries/states, we identified 6 control countries/ states with a similar population size and at least 3 times fewer deaths per population. We extracted data for 30 risk factors from publicly available, trusted sources. We compared case and control countries/states using the non-parametric Wilcoxon rank-sum test, and conducted a secondary cluster analysis to explore the relationship between the number of cases per population and the number of deaths per population using a scalable EM (expectation–maximization) clustering algorithm. Results: Statistically significant differences were found in 16 of 30 investigated risk factors, the most important of which were temperature, neonatal and under-5 mortality rates, the percentage of under-5 deaths due to acute respiratory infections (ARIs) and diarrhea, and tuberculosis incidence (p < 0.05) Conclusion: Countries with a higher burden of baseline pediatric mortality rates, higher pediatric mortality from preventable diseases like diarrhea and ARI, and higher tuberculosis incidence had lower rates of coronavirus disease 2019-associated mortality, supporting the hygiene hypothesis

    Evaluation of neuroendocrine markers in renal cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE), chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs) with special emphasis on patient outcome.</p> <p>Methods</p> <p>We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE) markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome.</p> <p>Results</p> <p>Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (<it>p </it>= 0.01). The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE.</p> <p>Conclusions</p> <p>Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.</p

    Site of Allergic Airway Narrowing and the Influence of Exogenous Surfactant in the Brown Norway Rat

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    Background: The parameters RN (Newtonian resistance), G (tissue damping), and H (tissue elastance) of the constant phase model of respiratory mechanics provide information concerning the site of altered mechanical properties of the lung. The aims of this study were to compare the site of allergic airway narrowing implied from respiratory mechanics to a direct assessment by morphometry and to evaluate the effects of exogenous surfactant administration on the site and magnitude of airway narrowing. Methods: We induced airway narrowing by ovalbumin sensitization and challenge and we tested the effects of a natural surfactant lacking surfactant proteins A and D (InfasurfH) on airway responses. Sensitized, mechanically ventilated Brown Norway rats underwent an aerosol challenge with 5 % ovalbumin or vehicle. Other animals received nebulized surfactant prior to challenge. Three or 20 minutes after ovalbumin challenge, airway luminal areas were assessed on snap-frozen lungs by morphometry. Results: At 3 minutes, RN and G detected large airway narrowing whereas at 20 minutes G and H detected small airway narrowing. Surfactant inhibited RN at the peak of the early allergic response and ovalbumin-induced increase in bronchoalveolar lavage fluid cysteinyl leukotrienes and amphiregulin but not IgE-induced mast cell activation in vitro. Conclusion: Allergen challenge triggers the rapid onset of large airway narrowing, detected by RN and G, and subsequen

    Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

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    Objectives—To identify SNPs associated with switching from an ACE-inhibitor to an angiotensin receptor blocker (ARB). Methods—Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the GoDARTS study in Scotland. Cases were intolerant subjects who switched from an ACE-inhibitor to an ARB, controls were subjects who used ACE-inhibitors continuously for at least 2 years and did not switch. GWAS using an additive model was run in these sets and results were meta-analysed using GWAMA. Results—972 cases out of 5 161 ACE-inhibitor starters were identified. 8 SNPs within 4 genes reached the GWAS significance level (P<5×10-8) in the meta-analysis (RBFOX3, GABRG2, SH2B1 and MBOAT1). The strongest associated SNP was located in an intron of RBFOX3, which contains a RNA binding protein (rs2061538: MAF=0.16, OR=1.52[95%CI: 1.32-1.76], p=6.2x10-9). Conclusions—These results indicate that genetic variation in abovementioned genes may increase the risk of ACE-inhibitors induced adverse reactions

    The relationship between patient physiology, the systemic inflammatory response and survival in patients undergoing curative resection of colorectal cancer

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    &lt;p&gt;Background: It is increasingly recognised that host-related factors may be important in determining cancer outcome. The aim was to examine the relationship between patient physiology, the systemic inflammatory response and survival after colorectal cancer resection.&lt;/p&gt; &lt;p&gt;Methods: Patients undergoing potentially curative resection of colorectal cancer were identified from a prospectively maintained database. Patient physiology was assessed using the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) criteria. The systemic inflammatory response was assessed using the modified Glasgow Prognostic Score (mGPS). Multivariate 5-year survival analysis was carried out with calculation of hazard ratios (HR).&lt;/p&gt; &lt;p&gt;Results: A total of 320 patients were included. During follow-up (median 74 months), there were 136 deaths: 83 colorectal cancer related and 53 non-cancer related. Independent predictors of cancer-specific survival were age (HR: 1.46, P&#60;0.01), Dukes stage (HR: 2.39, P&#60;0.001), mGPS (HR: 1.78, P&#60;0.001) and POSSUM physiology score (HR: 1.38, P=0.02). Predictors of overall survival were age (HR: 1.64, P&#60;0.001), smoking (HR: 1.52, P=0.02), Dukes stage (HR: 1.64, P&#60;0.001), mGPS (HR: 1.60, P&#60;0.001) and POSSUM physiology score (HR: 1.27, P=0.03). A relationship between mGPS and POSSUM physiology score was also established (P&#60;0.006).&lt;/p&gt; &lt;p&gt;Conclusion: The POSSUM physiology score and the systemic inflammatory response are strongly associated and both are independent predictors of cancer specific and overall survival in patients undergoing potentially curative resection of colorectal cancer.&lt;/p&gt

    The Transcriptome Analysis of Strongyloides stercoralis L3i Larvae Reveals Targets for Intervention in a Neglected Disease

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    BackgroundStrongyloidiasis is one of the most neglected diseases distributed worldwide with endemic areas in developed countries, where chronic infections are life threatening. Despite its impact, very little is known about the molecular biology of the parasite involved and its interplay with its hosts. Next generation sequencing technologies now provide unique opportunities to rapidly address these questions.Principal FindingsHere we present the first transcriptome of the third larval stage of S. stercoralis using 454 sequencing coupled with semi-automated bioinformatic analyses. 253,266 raw sequence reads were assembled into 11,250 contiguous sequences, most of which were novel. 8037 putative proteins were characterized based on homology, gene ontology and/or biochemical pathways. Comparison of the transcriptome of S. strongyloides with those of other nematodes, including S. ratti, revealed similarities in transcription of molecules inferred to have key roles in parasite-host interactions. Enzymatic proteins, like kinases and proteases, were abundant. 1213 putative excretory/secretory proteins were compiled using a new pipeline which included non-classical secretory proteins. Potential drug targets were also identified.ConclusionsOverall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic and metabolomic explorations of S. stercoralis, as well as a basis for applied outcomes, such as the development of novel methods of intervention against this neglected parasite

    Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells

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    Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ∼ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1 -/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process. © 2013 Li et al

    HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study

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    <p>Abstract</p> <p>Background</p> <p>In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment.</p> <p>Methods</p> <p>We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death.</p> <p>Results</p> <p>Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07–0.36), fluconazole use (HR 0.34; CI 0.18–0.64), and co-trimoxazole use (HR 0.41; CI 0.20–0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death.</p> <p>Conclusion</p> <p>Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.</p
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