Nonspecific colitis a forgotten entity in Central Sudan

Background: Nonspecific colitis is an inflammatory Bowel Disease (IBD) that runs a clinically benign course. Histopathologically it is characterized by superficial mucosal erosions with lymphocytic infiltration in the lamina propria with no granuloma. Aim of this study: is to describe the clinical presentation of Non-Specific Colitis (NSC), and to evaluate its response to 5-aminosalicylic acid (5-ASA) in Sudanese patients.Setting and Design: This study is a prospective cohort. A total of 26 patients presenting with bloody, mucoid diarrhoea, lower abdominal pain or colonic mass were included in the study.Methods and Materials: A total of 26 patients presenting with bloody mucoid diarrhoea, lower abdominal pain with or without colonic mass were included in the study. All patients underwent colonoscopy. Statistical analysis: A descriptive statistical analysis was done using SPSS.Results: 19 (%) of patients were males and 7 were females with male to female ratio of 3:1. The majority of patients 16 (61.6%) had bloody diarrhea while 18 (69.2%) opened their bowel 4-6 times a day. The majority 10 (38.8%) had rectum and sigmoid involvement. All patients showed a good response to 5-ASA.Conclusions: This study showed that NSC has clinical features that are very much similar to mild UC with a rather good clinical response to oral 5-ASA.Keywords: Nonspecific colitis, indeterminate colitis, 5-aminosaclyic acid

Detection of Optimum pH of Momordica balsamina Seeds Lectin

Background: Lectins are carbohydrate binding proteins of non-immune origin that reversibly and non-enzymatically bind carbohydrates with high specificity for the chemical structure of the glycan array without changing their structure.Objectives: The present study aimed to detect the optimum pH of Momordica balsamina seeds lectin (MbSL).Materials and Methods:A season fresh of Momordica balsamina fruit seeds were brought from urban areas of Sudan (Gadarif and north Kurdofan states), then the lectin was isolated from saline extract by affinity chromatography on alpha agarose lactose matrix then the purified lectin activity was evaluated in different buffers to detect the optimum pH.Results: The activity of the lectin remained stable in the pH range 2-12.Conclusion: A lactose-binding lectin from seeds of Momordica balsamina medicinal plant shares a high degree of similarity with other Cucurbitaceae family lectins in term of their physicochemical features including sugar specificity, effect of pH on lectin stability.Keywords: Momordica balsamina; lectin; seeds; plant lectin; pH; protein

Characterizing Family Physicians Who Refer to Telepsychiatry in Ontario

INTRODUCTION: Telepsychiatry can improve access to psychiatric services for those who otherwise cannot easily access care. Family physicians are gatekeepers to specialized care in Ontario, so it is essential to understand predictors relating to referrals to telepsychiatry to better plan services and increase telepsychiatry adoption. METHODS: This study used an annual retrospective cross-sectional study design to compare physicians who referred their patients to telepsychiatry each year from fiscal year (FY) 2008 to FY 2016. A 1-year (FY 2016) comparison of family physicians who referred to telepsychiatry (FPTs) compared to family physicians who did not refer to telepsychiatry (FPNTs) matched (1:2) by region was also conducted. Finally, we used statistical modeling to understand the predictors of referring to telepsychiatry among physicians. RESULTS: Between FY 2008 and FY 2016, the number of patients receiving telepsychiatry increased from 925 visits to 13,825 visits. Thirty-two percent of Ontario primary care physicians referred to telepsychiatry in 2016. Several characteristics were notably different between FPTs and FPNTs: FPTs were more likely to be from a residence with less than 10,000 people, to have more nurse practitioners in the practice, and to be from a family health team than FPNTs. Rostered patients of FPTs were more likely to reside in rural areas, have more clinical complexity, and to utilize more mental health services compared to FPNTs. CONCLUSIONS: There has been an increase in the use of telepsychiatry by patients and family physicians over the study period, although there remains opportunity for significant growth. Family physicians who live in rural areas, are part of an FHT, have more NPs, with more rural and complex patients were more likely to refer to telepsychiatry. As recent pro-telemedicine policies support the growth of telepsychiatry, this study will serve as an important baseline

Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes

Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses

Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data

<p>Abstract</p> <p>Background</p> <p>Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, <it>post hoc </it>tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has <it>a priori </it>information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches are biased by the researcher's assumptions, and some treatment-based patterns may fail to be detected using these approaches. Finally, different patterns may have different probabilities of occurring by chance, importantly influencing researchers' conclusions about a pattern and its constituent genes.</p> <p>Results</p> <p>We developed a four step, <it>post hoc </it>pattern matching (PPM) algorithm to automate single channel gene expression pattern identification/significance. First, 1-Way Analysis of Variance (ANOVA), coupled with <it>post hoc </it>'all pairwise' comparisons are calculated for all genes. Second, for each ANOVA-significant gene, all pairwise contrast results are encoded to create unique pattern ID numbers. The # genes found in each pattern in the data is identified as that pattern's 'actual' frequency. Third, using Monte Carlo simulations, those patterns' frequencies are estimated in random data ('random' gene pattern frequency). Fourth, a Z-score for overrepresentation of the pattern is calculated ('actual' against 'random' gene pattern frequencies). We wrote a Visual Basic program (StatiGen) that automates PPM procedure, constructs an Excel workbook with standardized graphs of overrepresented patterns, and lists of the genes comprising each pattern. The visual basic code, installation files for StatiGen, and sample data are available as supplementary material.</p> <p>Conclusion</p> <p>The PPM procedure is designed to augment current microarray analysis procedures by allowing researchers to incorporate all of the information from post hoc tests to establish unique, overarching gene expression patterns in which there is no overlap in gene membership. In our hands, PPM works well for studies using from three to six treatment groups in which the researcher is interested in treatment-related patterns of gene expression. Hardware/software limitations and extreme number of theoretical expression patterns limit utility for larger numbers of treatment groups. Applied to a published microarray experiment, the StatiGen program successfully flagged patterns that had been manually assigned in prior work, and further identified other gene expression patterns that may be of interest. Thus, over a moderate range of treatment groups, PPM appears to work well. It allows researchers to assign statistical probabilities to patterns of gene expression that fit <it>a priori </it>expectations/hypotheses, it preserves the data's ability to show the researcher interesting, yet unanticipated gene expression patterns, and assigns the majority of ANOVA-significant genes to non-overlapping patterns.</p

Lack of influence of the COX inhibitors metamizol and diclofenac on platelet GPIIb/IIIa and P-selectin expression in vitro

BACKGROUND: The effect of non-steroidal anti-inflammatory drugs (NSAIDs) for reduced platelet aggregation and thromboxane A(2 )synthesis has been well documented. However, the influence on platelet function is not fully explained. Aim of this study was to examine the influence of the COX-1 inhibiting NSAIDs, diclofenac and metamizol on platelet activation and leukocyte-platelet complexes, in vitro. Surface expression of GPIIb/IIIa and P-selectin on platelets, and the percentage of platelet-leukocyte complexes were investigated. METHODS: Whole blood was incubated with three different concentrations of diclofenac and metamizol for 5 and 30 minutes, followed by activation with TRAP-6 and ADP. Rates of GPIIb/IIIa and P-selectin expression, and the percentage of platelet-leukocyte complexes were analyzed by a flow-cytometric assay. RESULTS: There were no significant differences in the expression of GPIIb/IIIa and P-selectin, and in the formation of platelet-leukocyte complexes after activation with ADP and TRAP-6, regarding both the time of incubation and the concentrations of diclofenac and metamizol. CONCLUSIONS: Accordingly, the inhibitory effect of diclofenac and metamizol on platelet aggregation is not related to a reduced surface expression of P-selectin and GPIIb/IIIa on platelets

Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; A case series 2004 – 2006

<p>Abstract</p> <p>Background</p> <p>Human hepatitis E virus (HEV) infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV) infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV.</p> <p>Methods</p> <p>A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM) after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact.</p> <p>Results</p> <p>We interviewed 19 cases; 17 were male, median age 50 years (25–84 y), 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16) and icterus (n = 15). Sixteen ate pork ≥ once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV), two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home.</p> <p>Conclusion</p> <p>The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.</p

Predicting and Validating Protein Interactions Using Network Structure

Protein interactions play a vital part in the function of a cell. As experimental techniques for detection and validation of protein interactions are time consuming, there is a need for computational methods for this task. Protein interactions appear to form a network with a relatively high degree of local clustering. In this paper we exploit this clustering by suggesting a score based on triplets of observed protein interactions. The score utilises both protein characteristics and network properties. Our score based on triplets is shown to complement existing techniques for predicting protein interactions, outperforming them on data sets which display a high degree of clustering. The predicted interactions score highly against test measures for accuracy. Compared to a similar score derived from pairwise interactions only, the triplet score displays higher sensitivity and specificity. By looking at specific examples, we show how an experimental set of interactions can be enriched and validated. As part of this work we also examine the effect of different prior databases upon the accuracy of prediction and find that the interactions from the same kingdom give better results than from across kingdoms, suggesting that there may be fundamental differences between the networks. These results all emphasize that network structure is important and helps in the accurate prediction of protein interactions. The protein interaction data set and the program used in our analysis, and a list of predictions and validations, are available at http://www.stats.ox.ac.uk/bioinfo/resources/PredictingInteractions

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting