Axelsenkappel9170

A fosfomycin-resistant and carbapenemase (OXA-48)-producing Klebsiella pneumoniae isolate was recovered and whole-genome sequencing revealed an ISEcp1-bla CTX-M-14b tandemly inserted upstream of the chromosomally-encoded lysR-fosA locus. Quantitative evaluation of the expression of the lysR and fosA genes showed that this insertion brought a strong hybrid promoter leading to the overexpression of the fosA gene resulting in fosfomycin resistance. This work showed the concomitant acquisition of resistance to broad-spectrum cephalosporins and fosfomycin due to a single genetic event. Copyright © 2020 American Society for Microbiology.A four-year surveillance of carbapenem-resistant Acinetobacter spp. in Argentina identified 40 strains carrying bla NDM-1 Genome sequencing revealed that most were A. baumannii, while seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. bla NDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-baumannii strains. A resistance gene island carrying bla PER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains. Copyright © 2020 American Society for Microbiology.Tuberculosis (TB) drug development is dependent on informative trials to secure development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamid (PZA) are important components of recommended standard multi-drug treatments of TB. Paradoxically, in a Phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant drug effect was demonstrated for the two drugs using traditional statistical analysis. Using a model-based analysis we characterized statistically significant exposure-response relationships for both drugs that could explain the original findings of increase in colony forming units (CFU) with CLO treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make right decisions for advancement to further development. We propose that this quantitative semi-mechanistic approach provides a rational framework for analysing Phase IIa EBA studies, and can accelerate anti-TB drug development. Copyright © 2020 Faraj et al.Advances in single-cell RNA-seq (scRNA-seq) and computational analysis have enabled the systematic interrogation of the cellular composition of tissues. Combined with tools from developmental biology, cell biology, and genetics, these approaches are revealing fundamental aspects of tissue geometry and physiology, including the distribution, origins, and inferred functions of specialized cell types, and the dynamics of cellular turnover and differentiation. By comparing different tissues, such studies can delineate shared and specialized features of cell types and their lineage. read more Here, we compare two developmentally related murine epithelia, the airway and the small intestinal epithelia, which are both derived from the embryonic endodermal gut tube. We examine how airway and intestine generate and functionalize common archetypal cell types to fulfill similar shared physiologic functionalities. We point to cases in which similar cell types are repurposed to accommodate each tissue's unique physiologic role, and highlight tissue-specific cells whose specializations contribute to the distinct functional roles of each organ. We discuss how archetypal and unique cell types are incorporated within a cellular lineage, and how the regulation of the proportions of these cell types enables tissue-level organization to meet functional demands and maintain homeostasis. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.Treatment of type 1 diabetes with insulin injection is expensive, complicated, and insufficient. While cadaveric islet transplantations coupled with immunosuppressants can cure diabetes, the scarcity of acceptable islets is problematic. Developmental research on pancreas formation has informed in vitro differentiation of human pluripotent stem cells into functional islets. Although generating β cells from stem cells offers a potential cure for type 1 diabetes, several challenges remain, including protecting the cells from the immune system. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.Guidelines on the treatment of tuberculosis (TB) have essentially remained the same for the past 35 years, but are now starting to change. Ongoing clinical trials will hopefully transform the landscape for treatment of drug sensitive TB, drug resistant TB, and latent TB infection. Multiple trials are evaluating novel agents, repurposed agents, adjunctive host directed therapies, and novel treatment strategies that will increase the probability of success of future clinical trials. Guidelines for HIV-TB co-infection treatment continue to be updated and drug resistance testing has been revolutionized in recent years with the shift from phenotypic to genotypic testing and the concomitant increased speed of results. These coming changes are long overdue and are sorely needed to address the vast disparities in global TB incidence rates. TB is currently the leading cause of death globally from a single infectious agent, but the work of many researchers and the contributions of many patients in clinical trials will reduce the substantial global morbidity and mortality of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http//group.bmj.com/group/rights-licensing/permissions.OBJECTIVE To determine the incidence, demography and prognosis of vitamin D deficiency dilated cardiomyopathy (DCM) in Scotland over the last decade. STUDY DESIGN A retrospective review of cases of vitamin D deficiency DCM presenting to a national paediatric cardiac centre between 1 January 2008 and 1 January 2018. The departmental database and electronic and paper case notes were used to identify patients and extract data. RESULTS Six patients were identified (three male), three of whom were Caucasian. Median age at presentation was 206 days (range 2-268.) All six patients had high serum parathyroid hormone levels (median 45 pmol/L, range 27-120 pmol/L), a sensitive marker of total body calcium deprivation secondary to vitamin D deficiency. All patients demonstrated clinical and echocardiographic improvement following high dose vitamin D treatment. No patients required cardiac transplant, and only one patient required extracorporeal life support as a bridge to recovery. One patient failed to comply with medical management and died 5 months after initial diagnosis.