026). Importantly, we found clear differences between the scores of the four different biopsylocations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score. While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score. Total hip arthroplasty (THA) rates have increased dramatically in the recent decades worldwide, with Germany being one of the leading countries in the prevalence of THA. Simultaneously, a rising number of revision procedures is expected, which will put an enormous economic burden on future health care systems. Nationwide data provided by the Federal Statistical Office of Germany were used to quantify primary and revision arthroplasty rates as a function of age and gender. Projections were performed with use of Negative Binomial and Poisson regression models on historical procedure rates in relation to population projections from 2020 to 2060. A 62% increase in the incidence rate of primary THAs is projected until 2060. At the same time, the annual total number of revision procedures is forecast to rise about 40% by the year 2060. The highest numbers of revision arthroplasties were calculated around year 2043. The greatest proportions of revision surgery will be observed in women and in those aged 70years or older. The revision burden is projected to stabilize around 15% by 2060. The present projections allow a quantification of the increasing economic burden that (revision) THA will place on the German health care system in the upcoming decades. This study may serve as a model for other countries with similar demographic development as the country-specific approach predicts a substantial increase in the number of these procedures. This highlights the need for appropriate financial and human resource management in the future. The present projections allow a quantification of the increasing economic burden that (revision) THA will place on the German health care system in the upcoming decades. This study may serve as a model for other countries with similar demographic development as the country-specific approach predicts a substantial increase in the number of these procedures. This highlights the need for appropriate financial and human resource management in the future. Depression causes significant debilitating symptoms and economic burden. Current management is challenged by slow onset of action and modest efficacies of antidepressants; thus, the search for newer antidepressants remains relevant. https://www.selleckchem.com/products/bgb-290.html We evaluated the antidepressant effects of a kaurene diterpene, xylopic acid (XA), in zebrafish and mouse models. The chronic unpredictable stress (CUS) protocol in zebrafish and the tail suspension test (TST), forced swim test (FST), lipopolysaccharide-induced depression-like behaviour test (LID) and repeated open space swimming test (OSST) in mice were used. We further examined the impact of depleting monoamines on XA's antidepressant effects. The contribution of glutamatergic and nitrergic pathways on the antidepressant effect of XA in mice and XA's effects on 5-HT receptors and monoamine oxidase (MAO) enzymes were also evaluated. Finally, XA's influence on neuroprotection was evaluated by measuring BDNF and oxidative stress enzymes in whole brain. XA doses (1-10μM) in zebrafish and (10, 30, 100mgkg ) in mice exerted potent antidepressant-like potential in FST, TST, LID and showed fast-onset antidepressant-like property in the OSST. The antidepressant-like properties in mice were reversed by blocking synthesis/release of serotonin but not noradrenaline using p-chlorophenylalanine and α-methyl-p-tyrosine, respectively. This antidepressant-like effect was potentiated by D-cycloserine and Nω-Nitro-L-arginine methyl ester (L-NAME) but not by D-serine and L-arginine. XA also evoked partial agonist-like effects on 5-hydroxytrptamine receptors on the rat fundus but it did not have MAO inhibition effect. It also increased BDNF, glutathione and antioxidant enzymes. Therefore, xylopic acid possesses antidepressant-like effects largely mediated by serotonergic and neuroprotective mechanisms. Therefore, xylopic acid possesses antidepressant-like effects largely mediated by serotonergic and neuroprotective mechanisms. The goal of this retrospective observational study is to determine whether patients with and without central sensitization (CS) undergoing total knee arthroplasty (TKA) have similar preoperative expectations. It was hypothesized that the degree of preoperative expectations is higher in patients with CS than in those without. The data of 324 patients who underwent primary unilateral TKA for knee osteoarthritis were reviewed and CS was measured using the Central Sensitization Inventory (CSI), which is a validated self-reported questionnaire consisting of a total of 25 questions. CS was defined as a CSI score of 40 or more. Patient expectations were investigated using the Hospital for Special Surgery Knee Replacement Expectations Survey (HSS-KRES) comprising five categories including pain relief, baseline activity, high flexion activity, social activity, and psychological well-being. The expectations of patients, the Western Ontario and McMaster Universities arthritis index (WOMAC) and American Society of Anesthesiologists (ASA) classification scores were compared between the CS and non-CS groups. The top three patient expectations in both groups were pain relief, psychological well-being, and walking ability. The total score for the expectations was 55.0 ± 8.3 in the CS group and 52.3 ± 10.4 in the non-CS group, indicating that the expectations of the CS group were higher than the non-CS group before TKA (p < 0.05). When the items on the HSS-KRES scale and the five categories were compared, the CS group had significantly higher expectations for pain relief and psychological well-being than did the non-CS group (all p < 0.05). The expectations of patients with CS before TKA were higher than those without CS. Given the limited improvement in patient-reported outcome measures of patients with CS undergoing TKA, they should be counseled to be realistic especially with their preoperative expectations of pain relief and psychological well-being. III. III.