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•First detection in Ireland of an E. coliphylogroup A encoding blaNDM-5and mcr-1.1.•Genomic analysis identified 63 ARGs and 47 virulence factors.•Phenotypic resistance to carbapenem, 5th generation cephalosporins and colistin.•Fosfomycin resistance possibly due to chromosomal AcrAB-TolC/MdtABC efflux pumps.•Enhanced clinical and genomic surveillance necessary to monitor MDR E. coli.

The co-chaperone FKBP51, encoded by FKBP5gene, is recognized as a psychiatric risk factor for anxiety and depressive disorders due to its crucial role in the stress response. Another key modulator in stress response regulation is the corticotropin releasing hormone (CRH), which is co-expressed with FKBP51 in many stress-relevant brain-regions and cell-types. Together, they intricately influence the balance of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary stress response systems. Previous research underscores the potential moderating effects these genes have on the regulation of the stressful life events towards the vulnerability of major depressive disorder (MDD). However, the specific function of FKBP51 in CRH-expressing neurons remains largely unexplored. Here, through deep behavioral phenotyping, we reveal heightened stress effects in mice lacking FKBP51 in CRH co-expressing neurons (CRHFKBP5−/−), particularly evident in social contexts. Our findings highlight the importance of considering cell-type specificity and context in comprehending stress responses and advocate for the utilization of machine-learning-driven phenotyping of mouse models. By elucidating these intricacies, we lay down the groundwork for personalized interventions aimed at enhancing stress resilience and individual well-being.

Escherichia colisequence type (ST) 127 is a pandemic lineage that belongs to the extraintestial pathogenic (ExPEC) family, mainly associated with urinary tract infections and bloodstream infections. Here, we report the complete genome of an E. coliST 127 isolate which was identified in the saliva of a patient with treatment-resistant schizophrenia (TRS) exhibiting no signs of infection. The objective of this work is to determine the mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and virulence factors (VFs) that contribute to the pathogenicity of such ST127 isolates.

The Motocross Action Magazine features letters from readers expressing their opinions and suggestions regarding motocross events and tracks. Some readers appreciate the coverage of local races, while others suggest renaming certain sections of the magazine. Additionally, there is a request for more coverage of motocross events in the Czech Republic and praise for the challenging layout of the Glen Helen track. The magazine also includes a letter from a young reader who is knowledgeable about motocross terminology. [Extracted from the article]

This study investigates the effect of the nanofibrous polymeric structure of an adsorptive material, modified with an immobilized inorganic sorbent based on ferrous sulphate, on the capacity of the material to remove arsenic from contaminated water. Nanofibrous materials were prepared by electrospinning from polyurethane types selected using a primary adsorption test. The functional groups and chemical composition (FTIR, EDX), morphology (SEM, porometry) and hydrophilicity (contact angles) of the prepared nanostructured materials were determined in order to assess the effect of composition and structure on the removal of arsenic. The process of arsenic removal was monitored by atomic absorption spectroscopy (AAS). It was found that certain samples of polyurethanes, particularly self-synthesized aromatic polyurethane of an ester type, PU918, could remove arsenic by complexation on nitrogen in their polymer chains. The greatest efficiency for arsenic removal was ca.60% (initial cAs= 150 μg L−1). It was also found that adding even a small amount (1 wt%) of an inorganic adsorbent based on ferrous sulphate into the fibre mass of the nanofibrous structure would increase the efficiency up to 90% as a result of a chemical reaction between the additive and arsenic ions. The extent and rate of adsorption were described by kinetic and isotherm models. The adsorption process is well characterized by a pseudo-second-order kinetic model and both Freundlich and Langmuir isotherm models. High adsorption capacity and rate are the basis for the use of nanofibrous material in filters for arsenic separation.

Background: Decreased cerebral perfusion and oxygenation are common in hemodialysis patients. Magnitude of the arteriovenous fistula involvement in this phenomenon is not known. The aim of this study was to investigate the effect that a short-term arteriovenous fistula flow interruption has on cerebral oxygenation and to review and suggest possible explanations.Methods: In 19 patients, basic laboratory and clinical data were obtained and arteriovenous fistula flow volume was measured by ultrasonography. Baseline regional cerebral oxygen saturation (rSO2) was measured by near-infrared spectroscopy. Manual pressure was then applied on the fistula, resulting in total blood flow interruption. After 1 min of manual compression, rSO2and blood pressure values were noted again. The compression-related change in rSO2was assessed, as well as its association with arteriovenous fistula flow volume, blood pressure, and other parameters.Results: Mean cerebral rSO2increased after arteriovenous fistula compression (from 53.6% ± 11.4% to 55.6% ± 10.8%; p = 0.000001; 95% confidence interval = 1.39–2.56). The rSO2increase was higher in patients with lower rSO2at baseline (r = −0.46; p = 0.045).Conclusion: A significant rise in cerebral oxygenation was observed following the manual compression of arteriovenous fistula. Therefore, the arteriovenous fistula could have a role in impaired cerebral oxygenation in hemodialysis patients.

In a “kick and kill” strategy for human immunodeficiency virus (HIV) eradication, protective concentrations of antiretrovirals (ARVs) in the lymph node are important to prevent vulnerable cells from further HIV infection. However, the factors responsible for drug distribution and concentration into these tissues are largely unknown. Although humanized mice and nonhuman primates (NHPs) are crucial to HIV research, ARV tissue pharmacology has not been well characterized across species. This study investigated the influence of drug transporter expression, viral infection, and sex on ARV penetration within lymph nodes of animal models and humans. Six ARVs were dosed for 10 days in humanized mice and NHPs. Plasma and lymph nodes were collected at necropsy, 24 hours after the last dose. Human lymph node tissue and plasma from deceased patients were collected from tissue banks. ARV, active metabolite, and endogenous nucleotide concentrations were measured by liquid chromatography–tandem mass spectrometry, and drug transporter expression was measured using quantitative polymerase chain reaction and quantitative targeted absolute proteomics. In NHPs and humans, lymph node ARV concentrations were greater than or equal to plasma, and tenofovir diphosphate/deoxyadenosine triphosphate concentration ratios achieved efficacy targets in lymph nodes from all three species. There was no effect of infection or sex on ARV concentrations. Low drug transporter expression existed in lymph nodes from all species, and no predictive relationships were found between transporter gene/protein expression and ARV penetration. Overall, common preclinical models of HIV infection were well suited to predict human ARV exposure in lymph nodes, and low transporter expression suggests primarily passive drug distribution in these tissues.

The effect of a lifestyle intervention to reduce liver fat content in nonalcoholic fatty liver disease in humans is influenced by genetics. We hypothesized that the amino acid exchange in human Gly388Arg (mouse homolog: Gly385Arg) in fibroblast growth factor receptor 4 (FGFR4), which regulates bile acid, lipid, and glucose metabolism, could determine hepatic lipid accumulation and insulin sensitivity. Mechanisms of this substitution were studied in mice under normal chow and high-fat diets.

Background: Creation of vascular access leads to considerable local haemodynamic changes with decreased hand perfusion. Distal limb tissues then represent a model of hand ischaemia effect on muscles. The aim of our study was to investigate how the presence of vascular access influences the hand muscle strength in end-stage renal disease patients.Methods: We included 52 chronically haemodialysed patients with upper limb access without clinical signs of hand ischaemia. Muscle strength was evaluated by dynamometry. Finger pressure was measured on the second and fourth fingers and averaged for further analysis. Thenar tissue oxygenation (rSO2) was analysed using near-infrared spectroscopy. All examinations were performed in both the hands. Basic laboratory analysis was added. Data were processed with unpaired t-test and correlation analysis.Results: Hands with dialysis access had lower values of handgrip strength (54.2 ± 29.1 lbs vs 48.6 ± 23.4 lbs, p= 0.0006), systolic finger pressure (127.1 ± 32.0 mmHg vs 101.4 ± 31.6 mmHg, p< 10−8) and of thenar rSO2(45.8% ± 12.9% vs 42.5% ± 13.3%, p= 0.002). Muscle strength (handgrip) was directly related to the thenar oxygenation (r= 0.36; p= 0.014) and to the finger systolic pressure (r= 0.38; p= 0.007) on the access extremity. On the extremity without dialysis access, handgrip strength was inversely related to patient’s age (r= −0.41, p= 0.003), dialysis vintage (r= −0.32, p= 0.02) and red cell distribution width (r= −0.37, p= 0.01).Conclusion: The presence of dialysis access leads to the decrease of finger pressure, oxygenation, and also muscle strength even in the absence of clinically overt hand ischaemia. All these parameters are interrelated. This study underlines the consequences of inadequate muscle perfusion.