Herndonbuch1715

Trauma arising from landmines and improvised explosive devices promotes heterotopic ossification, the formation of extra-skeletal bone in non-osseous tissue. To date, experimental platforms that can replicate the loading parameter space relevant to improvised explosive device and landmine blast wave exposure have not been available to study the effects of such non-physiological mechanical loading on cells. Here, we present the design and calibration of three distinct in vitro experimental loading platforms that allow us to replicate the spectrum of loading conditions recorded in near-field blast wave exposure. We subjected cells in suspension or in a three-dimensional hydrogel to strain rates up to 6000 s-1and pressure levels up to 45 MPa. Our results highlight that cellular activation is regulated in a non-linear fashion - not by a single mechanical parameter, it is the combined action of the applied mechanical pressure, rate of loading and loading impulse, along with the extracellular environment used to convey the pressure waves. Finally, our research indicates that PO MSCs are finely tuned to respond to mechanical stimuli that fall within defined ranges of loading. Creative Commons Attribution license.OBJECTIVES Epidemiologic studies evaluating associations between specific arthritis medications and perinatal outcomes are limited. We evaluated the association between conventional synthetic DMARD (csDMARD) use among women with rheumatic disease (RD) and neonatal outcomes. METHODS We linked population-based data in British Columbia, Canada from 01/01/2002 to 12/31/2012 on all inpatient/outpatient visits and medications with a perinatal registry. For small-for-gestational-age (SGA) births, we assessed csDMARD exposure 90 days preconception or during pregnancy until date of delivery. For congenital anomalies, we determined csDMARD exposure 90 days preconception or during the first trimester. Subasumstat clinical trial We used multivariable logistic regression models fitted with generalised estimating equations and calculated post-hoc power. RESULTS There were 185 pregnancies in 175 women (31.3±5.4 years) and 6,064 pregnancies in 4,387 women (31.1±5.4 years) in the csDMARD exposed and unexposed groups, respectively. Hydroxychloroquine, azathioprine, sulfasalazine, and methotrexate exposure before or during pregnancy were not associated with SGA births. The most sufficiently powered analyses were those for hydroxychloroquine, where exposure during pregnancy resulted in an adjusted odds ratio (aOR) of 1.12 (95% confidence interval [CI], 0.65-1.94) for SGA births. Although post-hoc power calculations indicate less power to detect associations between csDMARDs and congenital anomalies, results indicate methotrexate exposure during the first trimester is associated with elevated odds for congenital anomalies (aOR 6.58, 95% CI 1.15-37.75). CONCLUSIONS Findings are consistent with current guidelines regarding specific csDMARD use during the perinatal period for women with RD. It is important to report well-designed epidemiologic studies to facilitate future RD/csDMARD-specific meta-analyses.OBJECTIVES We explored the burden of symptoms of anxiety and depression on health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA). METHODS Adults with RA participating in an observational cohort completed PROMIS tests of depression, anxiety, fatigue, physical function (PF), pain interference (PI), sleep disturbance, and participation in social roles and activities at the baseline visit. Clinical measures of disease status were also obtained. We used ANOVA and partial correlation adjusting for the swollen joint count (SJC) to examine associations of anxiety and depression with other aspects of HRQL. Mild and moderate-severe anxiety were defined as T-scores ≥55.4 and ≥ 62.3 and mild and moderate-severe depression was defined as ≥52.5 and ≥58.6 based on previous validated clinical thresholds. Multivariable linear regression (MVR) was used to identify predictors of emotional distress with a subset analysis of those in remission/low disease activity. RESULTS Of 196 RA participants, 18% had mild anxiety, 9% had moderate-severe anxiety, 18% had mild depression, and 14% had moderate-severe depression symptoms. Anxiety and depression scores were associated with significantly worse mean scores across HRQL domains (p less then 0.05). In MVR, depression (β=0.75, p less then 0.001), PF (β=0.14, p=0.024) and fatigue (β=0.15, p=0.015) predicted higher anxiety levels, whereas only anxiety predicted higher depression levels (β=0.70, p= less then 0.001). In subset analysis, PF no longer predicted higher anxiety levels. CONCLUSIONS Emotional distress is common in RA, even when disease is well controlled, with considerable impacts on other aspects of HRQL even at mild levels.OBJECTIVES Myositis autoantibodies show great utility in the diagnosis and clinico-serological phenotyping of idiopathic inflammatory myopathy (IIM). We identified a novel autoantibody against heat shock factor 1 (HSF1) and further evaluated its disease specificity and clinical significance in IIM patients. METHODS A human protein microarray was used to identify autoantibodies in myositis sera. ELISA, immunoblot and dot blot assays were applied to examine anti-HSF1 autoantibodies in IIM patients and controls. Immunofluorescence was used to detect HSF1 expression in muscle tissues. RESULTS Anti-HSF1 was identified as a novel autoantibody by protein microarray and the seroreactivity was confirmed by immunoprecipitation, ELISA, immunoblot and dot blot assays. Anti-HSF1 autoantibodies were present in 64/581 (11.0%) IIM, 4/37 (10.8%) rheumatoid arthritis, 5/40 (12.5%) primary Sjögren's syndrome, 2/40 (5%) systemic lupus erythematosus, while largely negative in healthy controls. Anti-HSF1 autoantibodies were significantly associated with pruritus, hypergammaglobulinaemia, and elevated erythrocyte sedimentation rate in IIM patients. Anti-HSF1 autoantibodies were more prevalent in cancer-associated myositis (CAM) compared to non-CAM patients (17.2% vs. 7.5%, p=0.009), nevertheless were undetectable in cancer controls. Meanwhile, cross-sectional and longitudinal analyses revealed positive correlations between anti-HSF1 levels and disease activity in IIM patients without cancer. Additionally, increased expression of HSF1 was found in regenerating muscle cells of myositis muscle tissues. CONCLUSIONS These data reveal anti-HSF1 as a new autoantibody associated with CAM in IIM. The autoimmunity against HSF1 may be involved in the immunopathogenesis of myositis.