• Lewis Bernard posted an update 5 hours, 32 minutes ago

    Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array-CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNAs), reducing the number of FISH experiments per case and yielding genome-wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra-low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNAs in BM PCs in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell-sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNAs were detected by aCGH and LDS in all but one case. Importantly, all CNAs identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNAs in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array-CGH and LDS was observed. This validates LDS as a novel and cost-efficient tool for the detection of CNAs in MM. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Close contact was first identified as the primary route of transmission for most respiratory infections in the early 20th century. In this review, we synthesize the existing understanding of the mechanisms of close contact transmission. We focus on two issues the mechanism of transmission in close contact, namely the transmission of the expired particles between two people, and the physical parameters of close contact that affect the exposure of particles from one individual to another, or how the nature of close contact plays a role in transmission. We propose the existence of three sub-routes of transmission short-range airborne, large droplets, and immediate body-surface contact. We also distinguish a “body contact,” which is defined with an interpersonal distance of zero, from a close contact. We demonstrate herein that the short-range airborne sub-route may be most common. The timescales over which data should be collected to assess the transmission risk during close contact events are much shorter than those required for the distant airborne or fomite routes. The current paucity of high-resolution data over short distances and timescales makes it very difficult to assess the risk of infection in these circumstances. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.When two or more bacterial species inhabit a shared niche, often, they must compete for limited nutrients. Iron is an essential nutrient that is especially scarce in the marine environment. Bacteria can use the production, release, and re-uptake of siderophores, small molecule iron chelators, to scavenge iron. Siderophores provide fitness advantages to species that employ them by enhancing iron acquisition, and moreover, by denying iron to competitors incapable of using the siderophore-iron complex. Here, we show that cell-free culture fluids from the marine bacterium Vibrio fischeri ES114 prevent growth of other vibrio species. Mutagenesis reveals the aerobactin siderophore as the inhibitor. Our analysis reveals a gene, that we name aerE, encodes the aerobactin exporter, and LuxT is a transcriptional activator of aerobactin production. In co-culture, under iron-limiting conditions, aerobactin production allows V. fischeri ES114 to competitively exclude Vibrio harveyi, which does not possess aerobactin production and uptake genes. By contrast, V. fischeri ES114 mutants incapable of aerobactin production lose in competition with V. harveyi. Introduction of iutA, encoding the aerobactin receptor, together with fhuCDB, encoding the aerobactin importer are sufficient to convert V. harveyi into an “aerobactin cheater”. This article is protected by copyright. All rights reserved.OBJECTIVE Systemic aminoglycosides remain a cornerstone of treatment for Cystic Fibrosis (CF) pulmonary exacerbations (PEx); however, the impact of aminoglycoside pharmacokinetics (PK) on outcomes is not well defined in adult CF patients. Our objective was to assess the impact of increasing PK exposures on the clinical outcomes of PEx treatment in adult CF patients receiving high-dose and standard-dose extended-interval aminoglycosides. METHODS We conducted a retrospective study of adult CF patients treated with an intravenous aminoglycoside for a PEx. Serum amikacin, gentamicin, and tobramycin levels and FEV1 data were used to evaluate exposure-response relationships. PK parameters were estimated using a Bayesian approach to obtain AUC0-24hr , Cmax0-24hr , Cmin0-24hr estimates. The primary efficacy endpoint was a 90% recovery of baseline FEV1 by 30 days post-treatment. Toxicity included signs or symptoms of ototoxicity, vestibular, or renal toxicity. Multivariate linear mixed-effects models of FEV1 were usedtrategies for this population. This article is protected by copyright. All rights reserved.BACKGROUND Torsade de pointes is a form of polymorphic ventricular tachycardia associated with heart rate-corrected QT (QTc ) interval prolongation. selleck compound With approximately 24-61% of critically ill patients experiencing QTc interval prolongation, a predictive tool to identify high-risk patients could assist in monitoring and management in the intensive care unit (ICU). The Tisdale et al. Risk Score (TRS) is a predictive tool that was developed and validated in a Cardiac Critical Care Unit. OBJECTIVES The objective of this study was to evaluate the predictive validity (sensitivity and specificity) and likelihood ratios of the TRS in a medical ICU. METHODS This was a longitudinal, retrospective, cohort study of consecutive patients who met the inclusion criteria from October 2017 to June 2018 with a sample size of 264 patients. The sample size was derived based on the number of TRS covariates and an exploratory variable. Baseline characteristics and risk factors were documented from electronic health records. The first occurrence of QTc interval prolongation, defined as a QTc interval >500ms or an increase ≥60ms above baseline, was the primary endpoint.