Replication of Association between ADAM33 Polymorphisms and Psoriasis

Polymorphisms in ADAM33, the first gene identified in asthma by positional cloning, have been recently associated with psoriasis. No replication study of this association has been published so far. Data available in the French EGEA study (Epidemiological study on Genetics and Environment of Asthma, bronchial hyperresponsivensess and Atopy) give the opportunity to attempt to replicate the association between ADAM33 and psoriasis in 2002 individuals. Psoriasis (n = 150) has been assessed by questionnaire administered by an interviewer and a sub-sample of subjects with early-onset psoriasis (n = 74) has been identified based on the age of the subjects at time of interview (<40 years). Nine SNPs in ADAM33 and 11 SNPs in PSORS1 were genotyped. Association analysis was conducted by using two methods, GEE regression-based method and a likelihood-based method (LAMP program). The rs512625 SNP in ADAM33 was found associated with psoriasis at p = 0.01, the usual threshold required for replication (OR [95% CI] for heterozygotes compared to the reference group of homozygotes for the most frequent allele = 0.61 [0.42;0.89]). The rs628977 SNP, which was not in linkage disequilibrium with rs512625, was significantly associated with early-onset psoriasis (p = 0.01, OR [95% CI] for homozygotes for the minor allele compared to the reference group = 2.52 [1.31;4.86]). Adjustment for age, sex, asthma and a PSORS1 SNP associated with psoriasis in the EGEA data did not change the significance of these associations. This suggests independent effects of ADAM33 and PSORS1 on psoriasis. This is the first study that replicates an association between genetic variants in ADAM33 and psoriasis. Interestingly, the 2 ADAM33 SNPs associated with psoriasis in the present analysis were part of the 3-SNPs haplotypes showing the strongest associations in the initial study. The identification of a pleiotropic effect of ADAM33 on asthma and psoriasis may contribute to the understanding of these common immune-mediated diseases

Health-related quality of life after vertebral or hip fracture: a seven-year follow-up study

<p>Abstract</p> <p>Background</p> <p>The negative impact of vertebral and hip low-energy fractures on health-related quality-of-life (HRQOL) has been demonstrated previously, but few prospective long-term follow-up studies have been conducted. This study aims to (i) investigate the changes and long-term impact of vertebral or hip fracture and between fracture groups on HRQOL in postmenopausal women prospectively between two and seven years after the inclusion fracture, (ii) compare HRQOL results between fracture and reference groups and (iii) study the relationship between HRQOL and physical performance, spinal deformity index and bone mineral density at seven-year follow-up.</p> <p>Methods</p> <p>Ninety-one women examined two years after a low-energy vertebral or hip fracture were invited to a new examination seven years after the diagnosis. HRQOL was examined using the SF-36 questionnaire and was compared with an age and sex-matched reference group. Physical function was assessed using tests and questionnaires. Bone mineral density was measured. Radiographs of the spine were evaluated using the visual semiquantitative technique. A longitudinal and cross-sectional design was used in this study. Statistical analyses included descriptive statistics, Student's <it>t</it>-tests, ANCOVA, and partial correlation.</p> <p>Results</p> <p>Sixty-seven women participated. In the 42 women (mean age 75.8, SD 4.7) with vertebral fracture as inclusion fracture, bodily pain had deteriorated between two and seven years and might be explained by new fracture. Remaining pronounced reduction of HRQOL was seen in all domains except general health and mental health at seven-year follow-up in women with vertebral fractures compared to the reference group (p < 0.05). All 25 women (mean age 75.0, SD 4.7) with hip fracture as inclusion fracture had no significant changes in HRQOL between two and seven years and did not differ from the reference group regarding HRQOL after seven years. The vertebral group had significantly lower values for bodily pain, vitality, role-emotional function and mental health compared to the hip group. HRQOL showed a positive relationship between physical activity, static balance and handgrip strength.</p> <p>Conclusion</p> <p>The long-term reduction of HRQOL in women with vertebral fracture emerged clearly in this study. The relationships between HRQOL and physical performance in women with vertebral and hip fracture raise questions for more research.</p

The Role of the Yap5 Transcription Factor in Remodeling Gene Expression in Response to Fe Bioavailability

The budding yeast Saccharomyces cerevisiae has developed several mechanisms to avoid either the drastic consequences of iron deprivation or the toxic effects of iron excess. In this work, we analysed the global gene expression changes occurring in yeast cells undergoing iron overload. Several genes directly or indirectly involved in iron homeostasis showed altered expression and the relevance of these changes are discussed. Microarray analyses were also performed to identify new targets of the iron responsive factor Yap5. Besides the iron vacuolar transporter CCC1, Yap5 also controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of Aft1 nuclear localization. Consistently, we show that in the absence of Yap5 Aft1 nuclear exclusion is slightly impaired. These studies provide further evidence that cells control iron homeostasis by using multiple pathways

Functional gait rehabilitation in elderly people following a fall-related hip fracture using a treadmill with visual context: design of a randomized controlled trial

Background: Walking requires gait adjustments in order to walk safely in continually changing environments. Gait adaptability is reduced in older adults, and (near) falls, fall-related hip fractures and fear of falling are common in this population. Most falls occur due to inaccurate foot placement relative to environmental hazards, such as obstacles. The C-Mill is an innovative, instrumented treadmill on which visual context (e. g., obstacles) is projected. The C-Mill is well suited to train foot positioning relative to environmental properties while concurrently utilizing the high-intensity practice benefits associated with conventional treadmill training. The present protocol was designed to examine the efficacy of C-Mill gait adaptability treadmill training for improving walking ability and reducing fall incidence and fear of falling relative to conventional treadmill training and usual care. We hypothesize that C-Mill gait adaptability treadmill training and conventional treadmill training result in better walking ability than usual care due to the enhanced training intensity, with superior effects for C-Mill gait adaptability treadmill training on gait adaptability aspects of walking given the concurrent focus on practicing step adjustments. Methods/design: The protocol describes a parallel group, single-blind, superiority randomized controlled trial with pre-tests, post-tests, retention-tests and follow-up. Hundred-twenty-six older adults with a recent fall-related hip fracture will be recruited from inpatient rehabilitation care and allocated to six weeks of C-Mill gait adaptability treadmill training (high-intensity, adaptive stepping), conventional treadmill training (high-intensity, repetitive stepping) or usual care physical therapy using block randomization, with allocation concealment by opaque sequentially numbered envelopes. Only data collectors are blind to group allocation. Study parameters related to walking ability will be assessed as primary outcome pre-training, post-training, after 4 weeks retention and 12 months follow-up. Secondary study parameters are measures related to fall incidence, fear of falling and general health. Discussion: The study will shed light on the relative importance of adaptive versus repetitive stepping and practice intensity for effective intervention programs directed at improving walking ability and reducing fall risk and fear of falling in older adults with a recent fall-related hip fracture, which may help reduce future fall-related health-care costs

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de)

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed