This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.
  Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate.
 
  Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients.
 
  Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD.  https://www.selleckchem.com/products/Eloxatin.html  Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation.
 
  FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.
 FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.The emergence and transmission of the mobile colistin resistance gene (mcr-1) threatened the extensive use of polymyxin antimicrobials. Accumulated evidence showed that the banning of colistin additive in livestock feed efficiently reduce mcr-1 prevalence, not only in animals but also in humans and environments. However, our previous study has revealed that a small proportion of Escherichia coli could continually carry chromosomally-encoded mcr-1. The chromosomally-encoded events, indicated the existence of stabilized heritage of mcr-1 and revealed a potential threat in the antimicrobial stewardship interventions, are yet to be investigated. In this study, we systematically investigated the genetic basis of chromosomally-encoded mcr-1 in prevalence and potential mechanisms of lineage, plasmid, insertion sequence, and phage. Our results demonstrated that the emergence of chromosomally-encoded mcr-1 could originate from multiple mechanisms, but mainly derived through the recombination of ISApl1/Tn6330. We reported a specific transmission mechanism, which is a phage-like region without lysogenic components, could associate with the emergence and stabilization of chromosomally-encoded mcr-1. These results highlighted the potential origin and risks of chromosomally-encoded mcr-1, which could be a heritable repository and thrive again when confronted with new selective pressures. To the best of our knowledge, this is the first study to systematically reveal the genomic basis of chromosomally-encoded mcr-1, and report a specific transmission pattern involved in phage-like region. Overall, we demonstrate the origin mechanisms and risks of chromosomally-encoded mcr-1. It highlights the need of public attention on chromosome-encoded mcr-1 to prevent from its reemergence.Structure-based virtual screening (VS) uses computer docking to prioritize candidate small-molecule ligands for subsequent experimental testing. Docking programs evaluate molecular binding in part by predicting the geometry with which a given compound might bind a target receptor (e.g., the docked "pose" relative to a protein target). Candidate ligands predicted to participate in the same intermolecular interactions typical of known ligands (or ligands that bind related proteins) are arguably more likely to be true binders. Some docking programs allow users to apply constraints during the docking process with the goal of prioritizing these critical interactions. But these programs often have restrictive and/or expensive licenses, and many popular open-source docking programs (e.g., AutoDock Vina) lack this important functionality. We present LigGrep, a free, open-source program that addresses this limitation. As input, LigGrep accepts a protein receptor file, a directory containing many docked-compound files, and a list of user-specified filters describing critical receptor/ligand interactions. LigGrep evaluates each docked pose and outputs the names of the compounds with poses that pass all filters. To demonstrate utility, we show that LigGrep can improve the hit rates of test VS targeting H. sapiens poly(ADPribose) polymerase 1 (HsPARP1), H. sapiens peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (HsPin1p), and S. cerevisiae hexokinase-2 (ScHxk2p). We hope that LigGrep will be a useful tool for the computational biology community. A copy is available free of charge at http//durrantlab.com/liggrep/ .
  Critically ill patients receiving invasive ventilation are at risk of sputum retention. Mechanical insufflation-exsufflation (MI-E) is a technique used to mobilise sputum and optimise airway clearance. Recently, interest has increased in the use of mechanical insufflation-exsufflation for invasively ventilated critically ill adults, but evidence for the feasibility, safety and efficacy of this treatment is sparse. The aim of this scoping review is to map current and emerging evidence on the feasibility, safety and efficacy of MI-E for invasively ventilated adult patients with the aim of highlighting knowledge gaps and identifying areas for future research. Specific research questions aim to identify information informing indications and contraindications to the use of MI-E in the invasively ventilated adult, MI-E settings used, outcome measures reported within studies, adverse effects reported and perceived barriers and facilitators to using MI-E reported.
 
  We will search electronic databases MEDLINE, EMBASE, CINAHL using the OVID platform, PROSPERO, The Cochrane Library, ISI Web of Science and the International Clinical Trials Registry Platform.