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Mobile colistin resistance enzyme MCR-3 is a phosphoethanolamine transferase modifying lipid A in Gram-negative bacteria. MCR-3 generally mediates low-level (≤8 mg L-1 ) colistin resistance among Enterobacteriaceae, but occasionally confers high-level (>128 mg L-1 ) resistance in aeromonads. Herein, it is determined that MCR-3, together with another lipid A modification mediated by the arnBCADTEF operon, may be responsible for high-level colistin resistance in aeromonads. Lipid A is the critical site of pathogens for Toll-like receptor 4 recognizing. However, it is unknown whether or how MCR-3-mediated lipid A modification affects the host immune response. Compared with the wild-type strains, increased mortality is observed in mice intraperitoneally-infected with mcr-3-positive Aeromonas salmonicida and Escherichia coli strains, along with sepsis symptoms. Further, mcr-3-positive strains show decreased clearance rates than wild-type strains, leading to bacterial accumulation in organs. The increased mortality is tightly associated with the increased tissue hypoxia, injury, and post-inflammation. MCR-3 expression also impairs phagocytosis efficiency both in vivo and in vitro, contributing to the increased persistence of mcr-3-positive bacteria in tissues compared with parental strains. This study, for the first time, reveals a dual function of MCR-3 in bacterial resistance and pathogenicity, which calls for caution in treating the infections caused by mcr-positive pathogens.Glycogen synthase kinase 3 beta (GSK-3β) is considered as a promising drug target for the treatment of Alzheimer's disease (AD). In the present study, two compound libraries were selected for virtual screening based on pharmacophore models of GSK-3β to discover new inhibitors. Nine potential hits were retained for biological investigation and four of these compounds showed GSK-3β inhibitory activity (with the IC50 values in sub-micromolar range on GSK-3β). Compounds 6 and 9 have good safety. They do not have any significant in vitro cytotoxicity against PC12 and SH-SY5Y neuroblastoma cells at concentrations up to 90 μM. Based on the inhibitory activity and druggability properties, compound 8 is the preferred molecule, and it is a promising lead for the development of the GSK-3β inhibitors for reducing the abnormal hyperphosphorylation of tau protein and relieving AD.

To examine impact of pre-existing and incident problematic musculoskeletal (MSK) areas after total knee replacement (TKR) on postoperative 60-month Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/function scores.

Using data from a randomized controlled trial of subjects undergoing TKR for osteoarthritis, we assessed problematic MSK areas in six body regions before TKR and 12, 24, 36, and 48 months after TKR. We defined the following two variables 1) density count (number of problematic MSK areas occurring after TKR; range 0-24) and 2) cumulative density count (problematic MSK areas both before and after TKR, categorized into four levels no preoperative areas and density count of 0-1 [reference group]; no preoperative areas and density count of 2 or more; one or more preoperative areas and density count of 0-1; and one or more preoperative areas and density count of 2 or greater). We evaluated the associations between categorized 60-month WOMAC and cumulative density count by oric musculoskeletal areas beyond the index knee-preoperatively and/or postoperatively-was associated with worse 60-month WOMAC pain/function score.The effort to develop an effective and safe temporomandibular joint (TMJ) disc substitute has been one of the mainstreams of tissue engineering. Biodegradable customized scaffolds could approach safety and effectiveness to regenerate a new autologous disc, rather than using non-biodegradable materials. However, it is still technically challenging to mimic the biomechanical properties of the native disc with biodegradable polymers. In this study, new 3D tailored TMJ disc implants were developed (1) Poly(glycerol sebacate) (PGS) scaffold reinforced with electrospun Poly(εcaprolactone) (PCL) fibers on the outer surface (PGS+PCL); (2) PCL and polyethylene glycol diacrylate (PEGDA) (PCL+PEGDA); and (3) PCL. The TMJ implants were tested in a randomized preclinical trial, conducted in 24 black Merino sheep TMJ, perfoming bilateral interventions. Histologic, imaging, and kinematics analysis was performed. No statistical changes were observed between the PGS+PCL disc and the control group. The PCL+PEGDA and PCL groups were associated with statistical changes in histology (p = 0.004 for articular cartilage mid-layer; p = 0.019 for structure changes and p = 0.017 for cell shape changes), imaging (p = 0.027 for global appreciation) and dangerous material fragmentation was observed. No biomaterial particles were observed in the multi-organ analysis in the different groups. The sheep confirmed to be a relevant animal model for TMJ disc surgery and regenerative approaches. The PCL and PCL+PEGDA discs presented a higher risk to increase degenerative changes, due to material fragmentation. None of the tested discs regenerate a new autologous disc, however, PGS+PCL was safe, demonstrated rapid resorption, and was capable to prevent condyle degenerative changes.African swine fever (ASF) has been endemic in sub-Saharan Africa since the 1960s. Following its introduction in Senegal, in 1957, ASF steadily progressed through West Africa, reaching Burkina Faso in 2003, and later Mali in 2016. Despite the heavy burden of disease on pig production, little information is available on the genetic diversity of Africa swine fever virus (ASFV) in Burkina Faso, Mali and Senegal. click here Here, we used real-time PCR ASFV to detect the ASFV genome in samples collected between 1989 and 2016, in Burkina Faso, Mali and Senegal, and conventional approaches for isolate characterization. The C-terminal end of the p72 protein gene, the full E183L gene and the central variable region (CVR) within the B602L gene in ASFV genome were sequenced and compared to publicly available sequences. ASFV genome was found in 27 samples, 19 from Burkina Faso, three from Mali and five from Senegal. The phylogenetic analyses showed that all viruses belong to genotype I, with the ASFVs from Burkina Faso and Mali grouping with genotype Ia and ASFV serogroup 4, and those from Senegal with genotype Ib and the ASFV serogroup 1. The analysis of the CVR tetrameric tandem repeat sequences (TRS) showed four TRS variants in Burkina Faso, two in Senegal and one in Mali. The three countries did not share any common TRS, and all CVRs of this study differed from previously reported CVRs in West Africa, except for Senegal. Three of the five isolates from Senegal fully matched with the CVR, p72 and p54 sequences from ASFV IC96 collected during the 1996 ASF outbreak in Ivory Coast. This study shows the spread of the same ASFV strains across countries, highlighting the importance of continuous monitoring of ASFV isolates. It also calls for an urgent need to establish a regional plan for the control and eradication of ASF in West Africa.

Long-term indwelling catheters assist people who are unable to use another bladder management method. However, urine leakage is a common problem with an indwelling urinary catheter. This study aims to determine whether a modified catheterisation technique would reduce urine leakage incidence.

Participants were randomly divided into conventional or modified catheterisation groups. In the modified technique group, the volume of fluid that needed to be injected into the balloon to obtain a suitable catheter front-end curvature (120-145°) was measured before catheterisation. Baseline characteristics and first-time success rates and procedure durations were similar between groups.

There were 30 patients in each group. Compared with conventional catheterisation, the modified catheterisation group had smaller residual urine volume (median 11mL Vs. 30.5mL, p<0.001) and more leakage-free days (30days Vs. 10days, p<0.001). Leakage-free survival was longer in the modified catheterisation group (p<0.001). The residual urine volume (>17 vs ≤17ml (median); incident rate ratio (IRR), 28.710; 95%CI, 4.114-200.331; p=0.001) was independently associated with urine leakage.

The modified catheterisation technique may reduce the incidence of urine leakage.

The modified catheterisation technique may reduce the incidence of urine leakage.Herein, a novel two-dimensional (2D) electronic-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b4,5-b¢]diselenophene was synthesized. Then three copolymers (PBDT-Se, PBDSe-T and PBDSe-Se) were obtained by manipulating the connected types and number of selenophene on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b4,5-b¢]diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films. The PBDSe-TY6 blend film exhibits the best absorption complementarity, the most distinctive face-on orientation with proper phase separation, the highest carrier mobilities, and the lowest charge recombination among three blend films. Finally, the PBDSe-TY6-based device delivers an impressive power conversion efficiency (PCE) of 14.50%, which is higher than that of PBDT-SeY6 and PBDSe-SeY6. Moreover, a decent open-circuit voltage (Voc) of 0.89 V with a remarkable small energy loss of 0.44 eV was achieved for PBDSe-TY6. The efficiency of 14.50% is the highest value for selenophene-containing copolymer-based binary organic solar cells (OSCs). Our systemic study provides evidence that introduction of 2D-benzo[1,2-b4,5-b¢]diselenophene as the new fused electron-rich unit with synergistic π-bridge into copolymeric donors is a valid strategy for providing high Voc and excellent PCE simultaneously in selenophene-based OSCs.Conditions prompting physicians and surgeons first adapting endoscopes to peer into joints were mainly the sort of synovial conditions that would concern today's rheumatologists. Rheumatologists were among the pre-World War II pioneers developing and documenting arthroscopy. The post-War father of modern arthroscopy, Watanabe, found rheumatologists among his early students, who took back the technique to their home countries, teaching orthopedists and rheumatologists alike. Rheumatologists described and analyzed the intra-articular features of their common diseases in the '60s and '70s. A groundswell of interest from academic rheumatologists in adapting arthroscopy grew considerably in the '90s with development of "needle scopes" that could be used in an office setting. Rheumatologists helped conduct the very trials the findings of which reduced demand for their arthroscopic services by questioning the efficacy of arthroscopic debridement in osteoarthritis (OA) and also developing biological compounds that greatly reduced the call for any resective intervention in inflammatory arthropathies. The arthroscope has proven an excellent tool for viewing and sampling synovium and continues to serve this purpose at several international research centers. While cartilage is now imaged mainly by magnetic resonance imaging, some OA features - such as a high prevalence of visible calcinosis - beg further arthroscopy-directed investigation. A new generation of "needle scopes" with far superior optics awaits future investigators, should they develop interest.