Cardiovascular disease in systemic sclerosis - an emerging association?

Microvascular disease is a prominent feature of systemic sclerosis (SSc) and leads to Raynaud's phenomenon, pulmonary arterial hypertension, and scleroderma renal crisis. The presence of macrovascular disease is less well established, and, in particular, it is not known whether the prevalence of coronary heart disease in SSc is increased. Furthermore, in terms of cardiac involvement in SSc, there remains conjecture about the relative contributions of atherosclerotic macrovascular disease and myocardial microvascular disease. In this review, we summarize the literature describing cardiovascular disease in SSc, discuss the pathophysiological mechanisms common to SSc and atherosclerosis, and review the surrogate markers of cardiovascular disease which have been examined in SSc. Proposed mediators of the vasculopathy of SSc which have also been implicated in atherosclerosis include endothelial dysfunction, a reduced number of circulating endothelial progenitor cells, and an increased number of microparticles. Excess cardiovascular risk in SSc is suggested by increased arterial stiffness and carotid intima thickening and reduced flow-mediated dilatation. Cohort studies of adequate size are required to resolve whether this translates into an increased incidence of cardiovascular events in patients with SSc

Alpenloopings in Heimatklänge : Jodeln als Globalisierungsbewegung zwischen Tradition und Experiment

The subject of my contribution is the functioning and effect of yodeling as an experimental form of vocals and singing as presented in Stefan Schwieterts documentary Heimatklänge [Sounds of home] (CH/D 2007); a recursive figure that co-constitutes what is identified as home and forges a sense of identity. Yodeling enables two home »loops« of a special kind: first, the recursive calling-singing in the Swiss Alps, which returns to inside the body as a result of a specific geographic location and its echo, and second, a worldwide sounds network, which through the art of the three Swiss vocal artists Erika Stucky, Noldi Alder, and Christian Zehnder, forms an acoustic bridge from Switzerland via Mongolia to the USA. The essay follows the associative structure of the ilm, which describes a circular movement that seeks to locate the concept of home while alternating in sounds and images between region and global, own and alien, traditional and experimental. With its description of the hypothesis of the origin of yodeling the study begins with a musicological perspective; next, it present an in-depth film analysis of Heimatklänges presentation of yodeling; finally, it formulates a globalization hypothesis in the context of culture studies, which in conjunction with the film endeavours to rethink the relationship between mountain landscape and people

Speeching: Mobile Crowdsourced Speech Assessment to Support Self-Monitoring and Management for People with Parkinson's

We present Speeching, a mobile application that uses crowdsourcing to support the self-monitoring and management of speech and voice issues for people with Parkinson's (PwP). The application allows participants to audio record short voice tasks, which are then rated and assessed by crowd workers. Speeching then feeds these results back to provide users with examples of how they were perceived by listeners unconnected to them (thus not used to their speech patterns). We conducted our study in two phases. First we assessed the feasibility of utilising the crowd to provide ratings of speech and voice that are comparable to those of experts. We then conducted a trial to evaluate how the provision of feedback, using Speeching, was valued by PwP. Our study highlights how applications like Speeching open up new opportunities for self-monitoring in digital health and wellbeing, and provide a means for those without regular access to clinical assessment services to practice-and get meaningful feedback on-their speech

Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

INTRODUCTION: The 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls. METHODS: We performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI. RESULTS: The medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46). CONCLUSIONS: RA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients

Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)-LRR oligomerization interface

Background Monogenic autoinflammatory disorders are characterized by dysregulation of the innate immune system, for example by gain-of-function mutations in inflammasome-forming proteins, such as NOD-like receptor family CARD-containing 4 protein (NLRC4). Objective Here we investigate the mechanism by which a novel mutation in the leucine-rich repeat (LRR) domain of NLRC4 (c.G1965C, p.W655C) contributes to autoinflammatory disease. Methods: We studied 2 unrelated patients with early-onset macrophage activation syndrome harboring the same de novo mutation in NLRC4. In vitro inflammasome complex formation was quantified by using flow cytometric analysis of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 techniques and lentiviral transduction were used to generate THP-1 cells with either wild-type or mutant NLRC4 cDNA. Cell death and release of IL-1β/IL-18 were quantified by using flow cytometry and ELISA, respectively. Results The p.W655C NLRC4 mutation caused increased ASC speck formation, caspase-1–dependent cell death, and IL-1β/IL-18 production. ASC contributed to p.W655C NLRC4–mediated cytokine release but not cell death. Mutation of p.W655 activated the NLRC4 inflammasome complex by engaging with 2 interfaces on the opposing LRR domain of the oligomer. One key set of residues (p.D1010, p.D1011, p.L1012, and p.I1015) participated in LRR-LRR oligomerization when triggered by mutant NLRC4 or type 3 secretion system effector (PrgI) stimulation of the NLRC4 inflammasome complex. Conclusion This is the first report of a mutation in the LRR domain of NLRC4 causing autoinflammatory disease. c.G1965C/p.W655C NLRC4 increased inflammasome activation in vitro. Data generated from various NLRC4 mutations provides evidence that the LRR-LRR interface has an important and previously unrecognized role in oligomerization of the NLRC4 inflammasome complex

Improving treatment with methotrexate in rheumatoid arthritis-development of a multimedia patient education program and the MiRAK, a new instrument to evaluate methotrexate-related knowledge

To develop and test an evidence-based, multimedia patient education program (MPEP) about methotrexate (MTX) treatment for rheumatoid arthritis (RA) and a new measure of patient knowledge [Methotrexate in Rheumatoid Arthritis Knowledge test (MiRAK)]