Construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire : a new tool for the evaluation of activity limitations in patients with rheumatoid arthritis

Objectives: To describe the construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire, a self-report tool to evaluate chronic activity limitations in patients with rheumatoid arthritis (RA). The BRADA was developed to assess the eligibility of patients with RA for financial and social support measures. Methods: The BRADA questionnaire evaluates functioning in 6 functional domains (mobility, nutrition, self care, household tasks, awareness of danger and communication) over the past week and the past 3 months. To assess the psychometric properties of the BRADA, patients with moderate to severe RA filled out the BRADA, HAQ-DI and SF-36 questionnaires twice, with a four-week interval. At each visit, the total number of swollen and tender joints, and global disease activity were recorded. DAS 28 was measured at the first visit. Internal consistency of items per domain was evaluated with Cronbach's alpha method. Intraclass correlation coefficient (ICC) analysis was used to assess test-retest reliability. BRADA scores were compared to HAQ, SF-36 scores and disease activity parameters with Spearman's Rho correlation coefficients to assess construct validity. Results: Experts considered the content and face validity of BRADA to be adequate. Internal consistency was satisfactory for all functional domains (alpha >0.75), as was the test-retest reliability (ICC 0.78). BRADA scores showed excellent correlation with other validated questionnaires in RA (HAQ-DI, SF-36) and with measures of disease activity (VAS, DAS28) (p<0.001). Conclusions: Its psychometric properties indicate that the BRADA questionnaire is a suitable instrument to evaluate disease-specific activity limitations in patients with RA

Assessment of activity limitations with the Health Assessment Questionnaire predicts the need for support measures in patients with rheumatoid arthritis : a multicenter observational study

Objective: This study investigated whether the Health Assessment Questionnaire (HAQ) can be used as an instrument to assess the need for social support measures that address activity limitations and participation issues in patients with rheumatoid arthritis (RA). Methods: This multicenter observational study included patients with RA and disease duration of at least one year, consulting their rheumatologist for routine evaluation of disease activity. In the single study visit data on demographics, disease history and current treatment were collected. DAS28 values were collected to evaluate current RA disease activity. Patients were asked to fill out the HAQ and SF-36 questionnaires. Receiver Operator Characteristics (ROC) curves were constructed to evaluate the performance of the HAQ, SF-36 and DAS28 in predicting the need for nine supporting measures available for chronically ill patients in the Belgian social security system. The expert opinion of the treating rheumatologist was used as a reference. Results: The study included 316 patients with a mean age of 59.8 +/- 12.6 years, disease duration of 11.4 +/- 9.3 years, mean DAS28 values of 2.83 +/- 1.17. Mean HAQ score was 0.95 +/- 0.73, mean SF-36 score 56.5 +/- 21.3. HAQ scores >1 were observed in 39.4% of patients. The area under the HAQ ROC curve was consistently >0.7 and higher for the HAQ than for SF-36 or DAS28 for all support measures. Rheumatologists on average recommended 3.67 support measures. Conclusion: The HAQ score was found to be a good predictor of the need for social support measures in patients with RA

Diffeomorphic Registration of Images with Variable Contrast Enhancement

Nonrigid image registration is widely used to estimate tissue deformations in highly deformable anatomies. Among the existing methods, nonparametric registration algorithms such as optical flow, or Demons, usually have the advantage of being fast and easy to use. Recently, a diffeomorphic version of the Demons algorithm was proposed. This provides the advantage of producing invertible displacement fields, which is a necessary condition for these to be physical. However, such methods are based on the matching of intensities and are not suitable for registering images with different contrast enhancement. In such cases, a registration method based on the local phase like the Morphons has to be used. In this paper, a diffeomorphic version of the Morphons registration method is proposed and compared to conventional Morphons, Demons, and diffeomorphic Demons. The method is validated in the context of radiotherapy for lung cancer patients on several 4D respiratory-correlated CT scans of the thorax with and without variable contrast enhancement

The First Korean Case of Camurati-Engelmann Disease (Progressive Diaphyseal Dysplasia) Confirmed by TGFB1 Gene Mutation Analysis

Camurati-Engelmann disease (CED) is an autosomal dominant progressive diaphyseal dysplasia caused by mutations in the transforming growth factor-β1 (TGFB1) gene. We report the first Korean family with an affected mother and son who were diagnosed with CED. The proband is a 19-yr-old male with a history of abnormal gait since the age of 2. He also suffered from proximal muscle weakness, pain in the extremities, and easy fatigability. Skeletal radiographs of the long bones revealed cortical, periosteal, and endosteal thickenings, predominantly affecting the diaphyses of the upper and lower extremities. No other bony abnormalities were noted in the skull and spine and no remarkable findings were seen on laboratory tests. The patient's mother had a long-standing history of mild limb pain. Under the impression of CED on radiographic studies, we performed mutation analysis. A heterozygous G to A transition at cDNA position +653 in exon 4 of the TGFB1 gene (R218H) was detected in the patient and his mother

A further cost for the sicker sex? Evidence for male-biased parasite-induced vulnerability to predation

Males are typically the sicker sex. Data from multiple taxa indicate that they are more likely to be infected with parasites, and are less ‘tolerant’, or less able to mitigate the fitness costs of a given infection, than females. One cost of infection for many animals is an increased probability of being captured by a predator. A clear, hitherto untested, prediction is therefore that this parasite-induced vulnerability to predation is more pronounced among males than females. We tested this prediction in the sexually size dimorphic guppy, Poecilia reticulata, in which females are typically larger than males. We either sham or experimentally infected guppies with Gyrodactylus turnbulli, elicited their escape response using an established protocol and measured the distance they covered during 60 ms. To discriminate between the effects of body size and those of other inherent sex differences, we size-matched fish across treatment groups. Infection with G. turnbulli reduced the distance covered during the escape response of small adults by 20.1%, whereas that of large fish was unaffected. This result implies that parasite-induced vulnerability to predation is male-biased in the wild: although there was no difference in escape response between our experimentally size-matched groups of males and females, males are significantly smaller across natural guppy populations. These results are consistent with Bateman’s principle for immunity: natural selection for larger body sizes and longevity in females seems to have resulted in the evolution of increased infection tolerance. We discuss the potential implications of male-biased parasite-induced vulnerability for the evolutionary ecology of this host-parasite interaction in natural communities

FlyMine: an integrated database for Drosophila and Anopheles genomics.

FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists

Camurati-Engelmann Disease: Unique Variant Featuring a Novel Mutation in TGFβ1 Encoding Transforming Growth Factor Beta 1 and a Missense Change in TNFSF11 Encoding RANK Ligand

We report a 32-year-old man and his 59-year-old mother with a unique and extensive variant of Camurati-Engelmann disease (CED) featuring histopathological changes of osteomalacia and alterations within TGFβ1 and TNFSF11 encoding TGFβ1 and RANKL, respectively. He suffered leg pain and weakness since childhood and reportedly grew until his late 20s, reaching 7 feet in height. He had deafness, perforated nasal septum, torus palatinus, disproportionately long limbs with knock-knees, low muscle mass, and pseudoclubbing. Radiographs revealed generalized skeletal abnormalities, including wide bones and cortical and trabecular bone thickening in keeping with CED, except that long bone ends were also affected. Lumbar spine and hip BMD Z-scores were + 7.7 and + 4.4, respectively. Biochemical markers of bone turnover were elevated. Hypocalciuria accompanied low serum 25-hydroxyvitamin D (25[OH]D) levels. Pituitary hypogonadism and low serum insulin-like growth factor (IGF)-1 were present. Karyotype was normal. Despite vitamin D repletion, iliac crest histology revealed severe osteomalacia. Exon 1 of TNFRSF11A (RANK), exons 2, 3, and 4 of LRP5, and all coding exons and adjacent mRNA splice junctions of TNFRSF11B (OPG), SQSTM1 (sequestosome 1), and TNSALP (tissue nonspecific alkaline phosphatase) were intact. His asymptomatic and less dysmorphic 5′11″ mother, also with low serum 25(OH)D, had milder clinical, radiological, biochemical, and histopathological findings. Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFβ1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFβ1, consistent with CED. The son was also homozygous for a single base transversion in TNFSF11, predicting a nonconservative amino acid change (c.107C > G, p.Pro36Arg) in the intracellular domain of RANKL that was heterozygous in his nonconsanguineous parents. This TNFSF11 variant was not found in the SNP Database, nor in published TNFSF11 association studies, but it occurred in four of the 134 TNFSF11 alleles (3.0%) we tested randomly among individuals without CED. Perhaps the unique phenotype of this CED family is conditioned by altered RANKL activity. © 2011 American Society for Bone and Mineral Research