Meldgaardbossen4965

Phospho-kinase analysis revealed activation of MAPK and RhoGTPase signaling pathways by osteoarthritic synovial fluid, which was confirmed by elevated transcriptional activity of Elk-1 and SRF. Microbiology inhibitor Inhibitor studies revealed that ERK played a central role in the loss of chondrocyte phenotype, while EGFR and downstream mediators p38, JNK and Rac/Cdc42 were essential for fibrosis-associated collagen expression. Finally, we identified EGF signaling as a key activator of chondrocyte proliferation.

Osteoarthritic synovial fluid promoted chondrocyte fibrosis and proliferation through EGF receptor activation and downstream MAPK and RhoGTPase signaling.

Osteoarthritic synovial fluid promoted chondrocyte fibrosis and proliferation through EGF receptor activation and downstream MAPK and RhoGTPase signaling.

To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research.

Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0=not at all important to 100=extremely important). Items scoring a mean of 70 or above were selected for inclusion.

Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment.

Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Compare baseline characteristics and change in outcomes in patients with symptomatic knee or hip OA participating in patient education and exercise therapy.

Longitudinal cohort study. Good Life with osteoArthritis in Denmark (GLAD®) is an 8-week patient education and supervised exercise program delivered by certified clinicians. Changes in pain intensity, Knee injury/Hip disability Osteoarthritis Outcome Scores' subscale Quality of Life (K/HOOS QOL), EuroQoL 5-Dimensions 5-Level (EQ-5D) and 40m walk test at ∼3 and 12 months were compared between knee and hip patients.

24,241 knee and 8,358 hip patients were included, with response rates of 75% and 60% at ∼3 and 12 months. Age, gender, symptom duration, pain medication use, pain intensity, physical function and quality of life were alike. More knee than hip patients were obese and had bilateral symptoms. At 3 months, clinically relevant improvements were seen in both knee and hip OA patients with clinically irrelevant between groups differences; 2.1 (1.5; 2.8) mm in pain intensity,-1.1 (-1.5;-0.7) point in K/HOOS QOL score,-0.010 (-0.013;-0.007) in EQ-5D index score and-0.02 (-0.02;-0.01) m/sec in walking speed. At 12 months the slight immediate differences were equalized.

Patients presenting with knee and hip OA in primary care were on average more alike than different. Following treatment, clinically relevant improvements were seen in both knee and hip OA patients at 3 and 12 months. Patients with knee and hip OA should be prioritized alike for treatment with patient education and supervised exercise therapy.

Patients presenting with knee and hip OA in primary care were on average more alike than different. Following treatment, clinically relevant improvements were seen in both knee and hip OA patients at 3 and 12 months. Patients with knee and hip OA should be prioritized alike for treatment with patient education and supervised exercise therapy.The aim of this study was to characterise a hospital outbreak of NDM-7-producing Klebsiella pneumoniae associated with the successful multidrug-resistant (MDR) high-risk clone ST11 between 2017 and 2019 in southern Spain. A total of 46 NDM-7-producing isolates were recovered during the outbreak, including 16 from clinical samples, 27 from surveillance samples and 3 from environmental samples. All isolates were MDR, including carbapenem-resistant. Pulsed-field gel electrophoresis using XbaI restriction enzyme (XbaI-PFGE) showed three pulsotypes belonging to three different clones by multilocus sequence typing (MLST) ST307 (1 isolate); ST152 (1 isolate); and ST11 (44 isolates). Representative isolates were selected for characterisation of blaNDM-7-carrying plasmids using PCR-based replicon typing and whole-genome sequencing analysis. IncX3 plasmids containing NDM-7 were identified in the three clones. The blaNDM-7-carrying plasmids from the ST307 and ST11 clones were identical and were very similar to the IncX3 NDM-7 plasmid previously described. The NDM-7 carbapenemase was introduced into the hospital by means of the ST307 clone, while the ST11 high-risk clone was responsible for NDM-7 dissemination. It is essential to develop and implement strategies to control the introduction and spread of successful MDR clones in hospitals that include active surveillance programmes to detect colonised patients.Tissue concentrations of caspofungin were determined in nine clinically relevant tissues taken during routine autopsy of 20 patients who had died during caspofungin treatment or within 23 days of cessation. The highest levels were achieved in liver, with concentrations ranging from ≤0.50 to 91.5 µg/g (0.60 µg/g 21 days after the last administration), followed by spleen ( less then 0.25-46.3 µg/g), kidney ( less then 0.25-33.6 µg/g) and lung ( less then 0.25-31.0 µg/g). Intermediate concentrations were found in pancreas, skeletal muscle, thyroid and myocardium. The lowest concentrations were found in brain; caspofungin was only detectable in six of 17 samples. Caspofungin concentrations exceeded the minimum inhibitory concentration values of pathogenic Candida spp. in most of the tissue samples taken from patients who had died during treatment, except in brain samples. These findings warrant clinical outcome studies to establish the optimal treatment for deep-seated candidiasis, and support the current recommendations against echinocandins for treatment of fungal meningoencephalitis.This study aimed to characterize the epidemiology and clinical outcomes of patients with bloodstream infections (BSIs) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in an OXA-48-predominant environment. This was a retrospective single-centre cohort study including all consecutive patients with CRKP BSIs treated between 1 January 2014 and 31 December 2018. Multivariate analysis, subgroup analysis and propensity-score-matched analysis were employed to analyse 30-day mortality as the primary outcome. Clinical cure at day 14 was also analysed for the whole cohort. In total, 124 patients with unique isolates met all the inclusion criteria. OXA-48 was the most common type of carbapenemase (85.5%). Inappropriate therapy was significantly associated with 30-day mortality [70.6% vs 39.7%, adjusted odds ratio (aOR) 4.65, 95% confidence interval (CI) 1.50-14.40, P=0.008] and 14-day clinical failure (78.5% vs 56.2%, aOR 3.14, 95% CI 1.09-9.02, P=0.033) in multivariate analyses. Among those treated appropriately, the 30-day mortality rates were similar in monotherapy and combination therapy arms (OR 2.85, 95% CI 0.68-11.95, P=0.15). INCREMENT CPE mortality score (aOR 1.16, 95% CI 1.01-1.33, P=0.029), sepsis at BSI onset (aOR 2.90, 95% CI 1.02-8.27, P=0.046), and inappropriate therapy (aOR 4.65, 95% CI 1.50-14.40, P=0.008) were identified as independent risk factors for 30-day mortality. Colistin resistance in CRKP had no significant impact on 30-day mortality. These results were also confirmed in all propensity-score-matched analyses and sensitivity analyses. Appropriate regimens were associated with better clinical outcomes than inappropriate therapies for BSIs with CRKP predominantly possessing OXA-48.16S rRNA methyltransferase (16S RMTase) genes confer high-level aminoglycoside resistance, reducing treatment options for multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa isolates (n = 221) exhibiting high-level pan-aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) were screened for 16S RMTase genes to determine their occurrence among isolates submitted to a national reference laboratory from December 2003 to December 2015. 16S RMTase genes were identified using two multiplex PCRs, and whole-genome sequencing (WGS) was used to identify other antibiotic resistance genes, sequence types (STs) and the genetic environment of 16S RMTase genes. 16S RMTase genes were found in 8.6% (19/221) of isolates, with rmtB4 (47.4%; 9/19) being most common, followed by rmtD3 (21.1%; 4/19), rmtF2 (15.8%; 3/19) and single isolates harbouring rmtB1, rmtC and rmtD1. Carbapenemase genes were found in 89.5% (17/19) of 16S RMTase-positive isolates, with blaVIM (52.9%; 9/17) being most common. 16S RMTase genes were found in 'high-risk' clones known to harbour carbapenemase genes (ST233, ST277, ST357, ST654 and ST773). Analysis of the genetic environment of 16S RMTase genes identified that IS6100 was genetically linked to rmtB1; IS91 to rmtB4, rmtC or rmtD3; ISCR14 to rmtD1; and rmtF2 was linked to Tn3, IS91 or Tn1721. Although 16S RMTase genes explained only 8.6% of pan-aminoglycoside resistance in the P. aeruginosa isolates studied, the association of 16S RMTase genes with carbapenemase-producers and 'high-risk' clones highlights that continued surveillance is required to monitor spread as well as the importance of suppressing the emergence of dually-resistant clones in hospital settings.Our previous studies have revealed that long noncoding RNA (lncRNA) AGXT2L1-22 was highly expressed in keratinocytes of psoriasis. However, the functions of lnc-AGXT2L1-22 in keratinocytes remain unknown. Meanwhile, co-expression network analysis indicated lnc-AGXT2L1-22 could interact with estrogen-related receptor alpha (ERRα). In this study, interleukin (IL)-17A could stimulate the production of lnc-AGXT2L1-22 in keratinocytes, thus establishing an in vitro cellular model of psoriasis. Lnc-AGXT2L1-22 was overexpressed using lentiviral-vector and ERRα was downregulated with small interfering RNA. Then the effects of lnc-AGXT2L1-22 and ERRα on viability, apoptosis, and cell cycle in IL-17A-stimulated keratinocytes were assessed by CCK-8, EdU assay, and flow cytometry. We found that lnc-AGXT2L1-22 and ERRα both resulted in higher proliferation ability, lower apoptosis rates, and reduction of G0/G1 phase proportion. Furthermore, lnc-AGXT2L1-22 could promote the expression of ERRα and siERRα antagonized the effects of lnc-AGXT2L1-22 on the phenotypes above in IL-17A-induced keratinocytes.