Metabolic features and glucocorticoid-induced comorbidities in patients with giant cell arteritis and polymyalgia rheumatica in a Dutch and Danish cohort

OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are age-associated inflammatory diseases that frequently overlap. Both diseases require long-term treatment with glucocorticoids (GCs), often associated with comorbidities. Previous population-based cohort studies reported that an unhealthier metabolic profile might prevent the development of GCA. Here, we report metabolic features before start of treatment and during treatment in patients with GCA and PMR. METHODS: In the Dutch GCA/PMR/SENEX (GPS) cohort, we analysed metabolic features and prevalence of comorbidities (type 2 diabetes, hypercholesterolaemia, hypertension, obesity and cataract) in treatment-naïve patients with GCA (n=50) and PMR (n=42), and compared those with the population-based Lifelines cohort (n=91). To compare our findings in the GPS cohort, we included data from patients with GCA (n=52) and PMR (n=25) from the Aarhus cohort. Laboratory measurements, comorbidities and GC use were recorded for up to 5 years in the GPS cohort. RESULTS: Glycated haemoglobin levels tended to be higher in treatment-naïve patients with GCA, whereas high-density lipoprotein, low-density lipoprotein and cholesterol levels were lower compared with the Lifelines population. Data from the Aarhus cohort were aligned with the findings obtained in the GPS cohort. Presence of comorbidities at baseline did not predict long-term GC requirement. The incidence of diabetes, obesity and cataract among patients with GCA increased upon initiation of GC treatment. CONCLUSION: Data from the GCA and PMR cohorts imply a metabolic dysregulation in treatment-naïve patients with GCA, but not in patients with PMR. Treatment with GCs led to the rise of comorbidities and an unhealthier metabolic profile, stressing the need for prednisone-sparing targeted treatment in these vulnerable patients

Women's Experiences and Views about Costs of Seeking Malaria Chemoprevention and other Antenatal Services: A Qualitative Study from two Districts in Rural Tanzania.

The Tanzanian government recommends women who attend antenatal care (ANC) clinics to accept receiving intermittent preventive treatment against malaria during pregnancy (IPTp) and vouchers for insecticide-treated nets (ITNs) at subsidized prices. Little emphasis has been paid to investigate the ability of pregnant women to access and effectively utilize these services. To describe the experience and perceptions of pregnant women about costs and cost barriers for accessing ANC services with emphasis on IPTp in rural Tanzania. Qualitative data were collected in the districts of Mufindi in Iringa Region and Mkuranga in Coast Region through 1) focus group discussions (FGDs) with pregnant women and mothers to infants and 2) exit-interviews with pregnant women identified at ANC clinics. Data were analyzed manually using qualitative content analysis methodology. FGD participants and interview respondents identified the following key limiting factors for women's use of ANC services: 1) costs in terms of money and time associated with accessing ANC clinics, 2) the presence of more or less official user-fees for some services within the ANC package, and 3) service providers' application of fines, penalties and blame when failing to adhere to service schedules. Interestingly, the time associated with travelling long distances to ANC clinics and ITN retailers and with waiting for services at clinic-level was a major factor of discouragement in the health seeking behaviour of pregnant women because it seriously affected their domestic responsibilities. A variety of resource-related factors were shown to affect the health seeking behaviour of pregnant women in rural Tanzania. Thus, accessibility to ANC services was hampered by direct and indirect costs, travel distances and waiting time. Strengthening of user-fee exemption practices and bringing services closer to the users, for example by promoting community-directed control of selected public health services, including IPTp, are urgently needed measures for increasing equity in health services in Tanzania

Teaching Medicine to Non-English Speaking Background Learners in a Foreign Country

Teaching abroad exposes medical educators to unfamiliar teaching methods and learning styles that can enhance their overall teaching repertoire. Based on the author’s experience teaching residents for one month at a community hospital in Japan and a review of the non-English speaking background (NESB) educational literature, pedagogical principles and lessons for successful international NESB instruction are outlined. These methods include understanding the dissimilar linguistic, cultural, and academic backgrounds of the learners, emphasizing pace and clarity of speech, presenting a conceptual framework instead of detailed discourse on subjects, and regular visual reinforcement of spoken words. The limitations introduced by the language barrier and the use of interpreters are briefly discussed. As society and institutions of higher learning become more global and multicultural, clinician–educators may benefit from teaching in other countries in order to enhance their teaching skills with NESB learners, both abroad and in their own institutions

An alginate-layer technique for culture of Brassica oleracea L. protoplasts

Ten accessions belonging to the Brassica oleracea subspecies alba and rubra, and to B. oleracea var. sabauda were used in this study. Protoplasts were isolated from leaves and hypocotyls of in vitro grown plants. The influence of selected factors on the yield, viability, and mitotic activity of protoplasts immobilized in calcium alginate layers was investigated. The efficiency of protoplast isolation from hypocotyls was lower (0.7 ± 0.1 × 106 ml−1) than for protoplasts isolated from leaf mesophyll tissue (2 ± 0.1 × 106 ml−1). High (70–90%) viabilities of immobilized protoplasts were recorded, independent of the explant sources. The highest proportion of protoplasts undergoing divisions was noted for cv. Reball F1, both from mesophyll (29.8 ± 2.2%) and hypocotyl (17.5 ± 0.3%) tissues. Developed colonies of callus tissue were subjected to regeneration and as a result plants from six accessions were obtained

Nonsense-Mediated Decay Enables Intron Gain in Drosophila

Intron number varies considerably among genomes, but despite their fundamental importance, the mutational mechanisms and evolutionary processes underlying the expansion of intron number remain unknown. Here we show that Drosophila, in contrast to most eukaryotic lineages, is still undergoing a dramatic rate of intron gain. These novel introns carry significantly weaker splice sites that may impede their identification by the spliceosome. Novel introns are more likely to encode a premature termination codon (PTC), indicating that nonsense-mediated decay (NMD) functions as a backup for weak splicing of new introns. Our data suggest that new introns originate when genomic insertions with weak splice sites are hidden from selection by NMD. This mechanism reduces the sequence requirement imposed on novel introns and implies that the capacity of the spliceosome to recognize weak splice sites was a prerequisite for intron gain during eukaryotic evolution

Prolonged Application of High Fluid Shear to Chondrocytes Recapitulates Gene Expression Profiles Associated with Osteoarthritis

BACKGROUND: Excessive mechanical loading of articular cartilage producing hydrostatic stress, tensile strain and fluid flow leads to irreversible cartilage erosion and osteoarthritic (OA) disease. Since application of high fluid shear to chondrocytes recapitulates some of the earmarks of OA, we aimed to screen the gene expression profiles of shear-activated chondrocytes and assess potential similarities with OA chondrocytes. METHODOLOGY/PRINCIPAL FINDINGS: Using a cDNA microarray technology, we screened the differentially-regulated genes in human T/C-28a2 chondrocytes subjected to high fluid shear (20 dyn/cm(2)) for 48 h and 72 h relative to static controls. Confirmation of the expression patterns of select genes was obtained by qRT-PCR. Using significance analysis of microarrays with a 5% false discovery rate, 71 and 60 non-redundant transcripts were identified to be ≥2-fold up-regulated and ≤0.6-fold down-regulated, respectively, in sheared chondrocytes. Published data sets indicate that 42 of these genes, which are related to extracellular matrix/degradation, cell proliferation/differentiation, inflammation and cell survival/death, are differentially-regulated in OA chondrocytes. In view of the pivotal role of cyclooxygenase-2 (COX-2) in the pathogenesis and/or progression of OA in vivo and regulation of shear-induced inflammation and apoptosis in vitro, we identified a collection of genes that are either up- or down-regulated by shear-induced COX-2. COX-2 and L-prostaglandin D synthase (L-PGDS) induce reactive oxygen species production, and negatively regulate genes of the histone and cell cycle families, which may play a critical role in chondrocyte death. CONCLUSIONS/SIGNIFICANCE: Prolonged application of high fluid shear stress to chondrocytes recapitulates gene expression profiles associated with osteoarthritis. Our data suggest a potential link between exposure of chondrocytes/cartilage to abnormal mechanical loading and the pathogenesis/progression of OA

Pleiotropic genes for metabolic syndrome and inflammation

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. (C) 2014 Elsevier Inc. All rights reserved