Rheuma-VOR study: optimising healthcare of rheumatic diseases by multiprofessional coordinating centres.

OBJECTIVES: Early diagnosis of inflammatory arthritis is critical to prevent joint damage and functional incapacities. However, the discrepancy between recommendations of early diagnosis and reality is remarkable. The Rheuma-VOR study aimed to improve the time to diagnosis of patients with early arthritis by coordinating cooperation between primary care physicians, specialists and patients in Germany. METHODS: This prospective non-randomised multicentre study involved 2340 primary care physicians, 72 rheumatologists, 4 university hospitals and 4 rheumatology centres in 4 German Federal States. The two coprimary endpoints (time to diagnosis and screening performance of primary care physicians) were evaluated for early versus late implementation phase. Additionally, time to diagnosis and secondary endpoints (decrease of disease activity, increase in quality of life and overall well-being, improvement of fatigue, depression, functional ability, and work ability, reduction in drug and medical costs and hospitalisation) were compared with a reference cohort of the German Rheumatism Research Centre (DRFZ) reflecting standard care. RESULTS: A total of 7049 patients were enrolled in the coordination centres and 1537 patients were diagnosed with a rheumatic disease and consented to further participation. A follow-up consultation after 1 year was realised in 592 patients. The time to diagnosis endpoint and the secondary endpoints were met. In addition, the calculation of cost-effectiveness shows that Rheuma-VOR has a dominant cost-benefit ratio compared with standard care. DISCUSSION: Rheuma-VOR has shown an improvement in rheumatological care, patient-reported outcome parameters and cost savings by coordinating the cooperation of primary care physicians, rheumatologists and patients, in a nationwide approach.

Health at the Intersections of Precarious Documentation Status and Gender-Based Partner Violence.

This article is based on qualitative research investigating Spanish-speaking immigrant women's experiences of gender-based intimate partner violence (GBPV) and help seeking in New Jersey (2006-2008). Methods included interviews with these women, health care and social service providers, and community members. This article reveals that as many immigrant women live at the intersections of structural, normalized, and gender-based partner violence, integrated social service responses emerge as key health care responses to GBPV. The health impacts of undocumented and precariously documented migration and GBPV demand policy interventions and dedication of resources to address the multi-faceted needs of this population.

Silica as a morphogenetically active inorganic polymer.

At present the scaffolds used for bioprinting of cells do not elicit morphogenetic responses in the cells. In the present study we approached a solution by studying the effect of an inorganic silica supplement added to an Na-alginate matrix. Bone- and osteoblast-like SaOS-2 cells were embedded into this organic polymeric matrix which was additionally enriched with 400 µM prehydrolyzed TEOS [tetra-ethoxy-silane], a source of ortho-silicate. In this silica-based matrix the cells synthesized hydroxyapatite crystallites after exposure to a mineralization activation cocktail composed of ß-glycerophosphate, ascorbic acid and dexamethasone. The degree of hydroxyapatite synthesis, determined by staining the cells with the OsteoImage dye, strongly increased after exposure of the cells to silica. In a previous study we reported that ortho-silicate induces the expression of the gene encoding BMP-2 [bone morphogenetic protein-2]. Now we asked the question whether, in the presence of the mineralization activation cocktail, silica induces differentially the fibrillar proteins type I collagen [COLI] and type V collagen [COLV], as well as the non-collagenous proteins alkaline phosphatase [ALP], osteopontin [OPN], osteonectin [ON], osteocalcin [OC], and bone sialoprotein II [BSP]. Those expression values were correlated with the transcript levels of RUNX2 [Runt-related transcription factor 2]. The data show that the steady-state transcript level of RUNX2 remained unchanged in the presence of silica, while this inorganic polymer caused an elevated BMP-2 transcript level, and simultaneously also a significant upregulation of the COLI, COLV, OPN and ON genes. In contrast, the level of expression of OC and BSP remained unchanged in the presence of silica. It is concluded that silica causes its morphogenetic effect with respect to some bone-specific genes, COLI, COLV, OPN and ON, in a RUNX2-independent way.

Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein.

Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the Alzheimer disease amyloid beta peptide (Abeta). The molecular mechanisms underlying the control of APP shedding remain little understood but are in part dependent on the low density lipoprotein receptor-related protein (LRP), which is involved in APP endocytosis. Here, we show that the APP homolog APLP1 (amyloid precursor-like protein 1) influences APP shedding. In human embryonic kidney 293 cells expression of APLP1 strongly activated APP shedding by alpha-secretase and slightly reduced beta-secretase cleavage. As revealed by domain deletion analysis, the increase in APP shedding required the NPTY amino acid motif within the cytoplasmic domain of APLP1. This motif is conserved in APP and is essential for the endocytosis of APP and APLP1. Unrelated membrane proteins containing similar endocytic motifs did not affect APP shedding, showing that the increase in APP shedding was specific to APLP1. In LRP-deficient cells APLP1 no longer induced APP shedding, suggesting that in wild-type cells APLP1 interferes with the LRP-dependent endocytosis of APP and there by increases APP alpha-cleavage. In fact, an antibody uptake assay revealed that expression of APLP1 reduced the rate of APP endocytosis. In summary, our study provides a novel mechanism for APP shedding, in which APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage.