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  • Tobin Seerup posted an update 3 weeks ago

    TRIAL REGISTRATION German Clinical Trials Register (DRKS) DRKS00013456. January 3rd 2018. World Health Organization Trial Registration Data Set Universal Trial number (UTN) U1111-1205-6181. November 23rd 2017.BACKGROUND Bleeding as an adverse event following immunization (AEFI) that is rarely reported in children, although it can be a parental concern. Bleeding episodes ranging in severity from mild to severe and defined as any external and/or internal bleeding can be caused by acquired or hereditary disorders. This study analyzes whether bleeding episodes in children that were recorded as AEFIs are causally associated with immunization and elaborates their etiology. METHODS A cross-sectional study of 388 AEFI cases in children from West Java Provincial Committee in Indonesia confirmed by case findings from 2000 until 2017. RESULTS Of the total number of cases studied, 55 (14%) involved children aged 5 days to 12 years who presented with bleeding and were referred to a provincial hospital. Analysis revealed that 32 cases were most likely caused by acquired prothrombin complex deficiency (APCD) and 30 of these APCD cases were strongly suspected to be manifestations of vitamin K deficiency bleeding (VKDB). All VKDB subjects were aged 5 days to 3 months without a history of administration of prophylactic vitamin K. When a World Health Organization classification was used, most bleeding cases in this study became coincidental events with a temporal association with immunization. A causality assessment suggested that these cases were causally unrelated. CONCLUSION Most cases of bleeding reported as an AEFI were found to be VKDB, which is considered a coincidental event following immunization with a temporal association, and an unrelated category based on the results of a causality assessment. Vitamin K should be administered to all newborns as a prophylactic and AEFI surveillance should be improved based on the low numbers of AEFI reported in Indonesia.INTRODUCTION The occurrence of cardiovascular diseases and metabolic disorders steadily increases with the body mass index (BMI). Since the latter is not the best and earliest indicator of obesity and cardiovascular risk, the aim of the study was to evaluate some potential biological markers that would allow us to detect children and adolescents at higher risk at an early stage. METHODS A sample of 330 children and adolescents were included in the study and divided into four groups obese patients with hypertension, normal-weight patients with hypertension, patients with mildly elevated lipids and a control group of healthy children and adolescents. Some clinical parameters (age, body weight, body height, BMI, waist circumference, hip circumference, blood pressure), biochemical parameters (glucose, total cholesterol, triglycerides, HDL, LDL, apolipoprotein A1, homocysteine) and biological markers of obesity (ghrelin, adiponectin, leptin) were evaluated. RESULTS Ghrelin and adiponectin were found to have a strological markers of obesity are useful early markers for identifying groups of patients that are at cardiovascular risk.BACKGROUND Tuberculosis (TB), particularly multi- and or extensive drug resistant TB, is still a global medical emergency. Whole genome sequencing (WGS) is a current alternative to the WHO-approved probe-based methods for TB diagnosis and detection of drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). This study compared WGS and clinical data in participants with TB. RESULTS This cohort study performed WGS on 87 from MTBC DNA isolates, 57 (66%) and 30 (34%) patients with drug resistant and susceptible TB, respectively. Drug resistance was determined by Xpert® MTB/RIF assay and phenotypic culture-based drug-susceptibility-testing (DST). WGS and bioinformatics data that predict phenotypic resistance to anti-TB drugs were compared with participant’s clinical outcomes. They were 47 female participants (54%) and the median age was 35 years (IQR) 29-44). Twenty (23%) and 26 (30%) of participants had TB/HIV co-infection BMI  less then  18 kg/m2 respectively. MDR-TB participants had MTBC with multiple mutant genes, compared to those with mono or polyresistant TB, and the majority belonged to lineage 3 Central Asian Strain (CAS). Also, MDR-TB was associated with delayed culture-conversion (median IQR (83 60-180 vs. 5130-66) days). WGS had high concordance with both culture-based DST and Xpert® MTB/RIF assay in detecting drug resistance (kappa = 1.00). CONCLUSION This study offers comparison of mutations detected by Xpert and WGS with phenotypic DST of M. tuberculosis isolates in Tanzania. The high concordance between the different methods and further insights provided by WGS such as PZA-DST, which is not routinely performed in most resource-limited-settings, provides an avenue for inclusion of WGS into diagnostic matrix of TB including drug-resistant TB.BACKGROUND ChIP (Chromatin immunoprecipitation)-exo has emerged as an important and versatile improvement over conventional ChIP-seq as it reduces the level of noise, maps the transcription factor (TF) binding location in a very precise manner, upto single base-pair resolution, and enables binding mode prediction. Availability of numerous peak-callers for analyzing ChIP-exo reads has motivated the need to assess their performance and report which tool executes reasonably well for the task. RESULTS This study has focussed on comparing peak-callers that report direct binding events with those that report indirect binding events. The effect of strandedness of reads and duplication of data on the performance of peak-callers has been investigated. The number of peaks reported by each peak-caller is compared followed by a comparison of the annotated motifs present in the reported peaks. The significance of peaks is assessed based on the presence of a motif in top peaks. Indirect binding tools have been compared on the basis of their ability to identify annotated motifs and predict mode of protein-DNA interaction. CONCLUSION By studying the output of the peak-callers investigated in this study, it is concluded that the tools that use self-learning algorithms, i.e. Selleck Polyethylenimine the tools that estimate all the essential parameters from the aligned reads, perform better than the algorithms which require formation of peak-pairs. The latest tools that account for indirect binding of TFs appear to be an upgrade over the available tools, as they are able to reveal valuable information about the mode of binding in addition to direct binding. Furthermore, the quality of ChIP-exo reads have important consequences on the output of data analysis.