Millsdueholm3319

Receptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.

RIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or

-deficient (



) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.

RIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly,

deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were rereat NASH and arrest disease progression.

Peripherally inserted central catheters (PICCs) provide reliable intravenous access for delivery of parenteral therapy. Yet, little is known about PICC care practices or how they vary across hospitals. We compared PICC-related processes across hospitals with different insertion delivery models.

We used a descriptive qualitative methodology and a naturalist philosophy, with site visits to conduct semistructured interviews completed between August 2018 and January 2019. Study sites included five Veterans Affairs Medical Centres, two with vascular access teams (VATs), two with PICC insertion primarily by interventional radiology (IR) and one without on-site PICC insertion capability. Interview participants were healthcare personnel (n=56), including physicians, bedside and vascular access nurses, and IR clinicians. Data collection focused on four PICC domains use and decision-making process, insertion, in-hospital management and patient discharge education. We used rapid analysis and a summary matrix to compthis variation are highlighted.Reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection have raised important questions about the strength and durability of the immune response to primary infection, which are key factors in predicting the course of the pandemic. Identifying reinfection requires detecting the virus at two different time points and using viral genomic data to distinguish reinfection from persistent viral carriage. This process is hindered by challenges of logistics and capacity, such as banking samples from primary infection and performing viral genome sequencing. These challenges may help to explain why very few cases have been described to date. In addition, reinfection may be a rare phenomenon, but detailed prospective studies are needed to rigorously assess its frequency. To provide context for future investigations of SARS-CoV-2 reinfection, we review 16 cases that have been published to date or are available in preprint. Reinfection occurred across demographic spectra and in patients whose initial infections were both asymptomatic/mild and moderate/severe. For cases in which severity could be compared between episodes, half of reinfections were less severe, raising the possibility of partial immune protection. Although many patients had a positive total immunoglobulin or IgG result at the time of reinfection, very little examination of their immune response was performed. AUPM-170 in vivo Further work is needed to elucidate the frequency, determinants, and consequences of SARS-CoV-2 reinfection. Establishing the necessary frameworks for surveillance and investigation will rely heavily on clinical laboratories and clinical investigators, and we propose several considerations to guide the medical community in identifying and characterizing SARS-CoV-2 reinfections.Clinical chemistry laboratories implemented fully automated devices decades before microbiologists started their subtle approaches to follow. Meanwhile several papers have been published about reduced time to reports, faster workflows, and increased sensitivity as results of lab automation. While the journey of automating microbiology workflows step by step was fascinating and beneficial, monetary aspects were uncommon in most publications. In this issue of the Journal of Clinical Microbiology, K. Culbreath, H. Piwonka, J. Korver, and M. Noorbakhsh (J Clin Microbiol 59e01969-20, https//doi.org/10.1128/JCM.01969-20) calculate the benefits of total lab automation in terms of cost savings and lab efficiency in a "tale of four laboratories." The authors here provide facts and solid calculations about the benefits achieved in four different-sized labs after implementation of full laboratory automation.A series of clinical NDM-5-producing Escherichia coli isolates obtained from two surveillance networks for carbapenem-producing Enterobacterales from 2018 to 2019, namely, Switzerland (NARA) and Germany (SurvCARE), were analyzed. The 33 NDM-5-producing E. coli isolates were highly resistant to β-lactams, including novel β-lactam/β-lactamase inhibitor combinations (ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam), and remained susceptible to fosfomycin, colistin, and tigecycline. These isolates were assigned to different sequence types (STs) and indicated a predominance of isolates exhibiting ST167 in Switzerland and Germany (n = 10) (phylogenetic group C), followed by ST405 (n = 4) (phylogenetic group E), ST1284 (n = 4) (phylogenetic group C), and ST361 (n = 4) (phylogenetic group C). The blaNDM-5 gene was predominantly present on an IncF-type plasmid (n = 29) and, to a lesser extent, on the narrow-host-range IncX3 plasmid (n = 4). Sequence analyses of eight NDM-5 plasmids indicated that NDM-5-encoding F-type plasmids varied in size between 86 and 132 kb. The two IncX3 plasmids pCH8NDM5 and pD12NDM5 were 46 and 45 kb in size, respectively. The highly conserved blaNDM-5 genetic surrounding structures (ΔISAba125-blaNDM-5-bleMBL-trpT-dsbD-IS26) of both the F-type and IncX3 plasmids suggested a common genetic origin. The emergence of the NDM-5 carbapenemase was evidenced in particular for the E. coli ST167 clone, which is a successful epidemic clone known to be associated with both multiresistance and virulence traits and is therefore of high public health concern. The occurrence of clonally related NDM-5-producing E. coli isolates in Switzerland and Germany further indicates the international spread of this multidrug-resistant superbug at least throughout Europe.