PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_891G, PADI4_901T and PADI4_921G gene polymorphisms were associated with RA susceptibility (OR = 1.34, p = 0.04; OR = 1.35, p = 0.03; OR = 1.34, p = 0.04; respectively). The GTG haplotype was also significantly associated with RA (OR = 2.27 95%CI = 1.18–4.41; p = 0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.     

Neural correlates of self‐injurious behavior in Prader–Willi syndrome

Individuals with Prader–Willi syndrome (PWS), a genetic disorder caused by mutations to the q11‐13 region on chromosome 15, commonly show severe skin‐picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6–25 years, who showed severe skin‐picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI‐safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin‐picking behavior compared with nonpicking episodes. Scores obtained on the Self‐Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin‐picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin‐picking behaviors in PWS. Implications for treatments are discussed. Hum Brain Mapp 36:4135–4143, 2015. © 2015 Wiley Periodicals, Inc.     

The stability of coping strategies in older adults with osteoarthritis and the ability of these strategies to predict changes in depression,disability, and pain

Objectives: Given the chronically painful, incurable nature of osteoarthritis, effective cognitive and behavioral coping strategies may be critical for older adults with the disease. Little is known about how and why coping changes over time, nor about stability of coping strategies in persons with osteoarthritis. The aims of this work were to examine the structure of coping in older adults with osteoarthritis, the association of coping strategies with well-being, the stability of coping over time, and its association with changes in well-being over the same period.

Method: In a cross-sectional study, 199 older adults with osteoarthritis of the knee were assessed at baseline and two-years’ follow-up. Items from two coping scales were factor analyzed, and Pearson's correlations and paired-samples t-tests assessed relative and absolute stability of the resultant coping strategies. CFA assessed the stability of the factor structure itself. Ordinary least-squares regression analyses examined the impact of change in coping on well-being.

Results: A five-factor coping solution emerged: stoicism, refocusing, problem-solving, wishful-thinking, and emotion-focused coping. The factor structure showed stability over the two-year period. Absolute stability of strategies varied, indicating that change in coping styles was possible.

Conclusion: Changes in coping style predicts future well-being; however, coping remains malleable with age and maladaptive strategies can be effectively targeted. Greater knowledge of the utility or maladaptive nature of a given strategy may help guide decisions about interventions for patients with osteoarthritis and encourage more adaptive coping styles.     

The ability of people with intellectual disability to use inhalers – an exploratory mixed methods study

Objective: This aim of this study was to assess inhaler technique of people with intellectual disability (ID), and evaluate the effectiveness of teaching with respect to their individual ability to adopt correct technique. Methods: Seventeen people with ID were recruited through existing networks of general practitioners and disability support organisations. Inhaler technique was assessed using validated checklists and placebo devices, followed by provision of individualised training. The educational interaction between participant and researcher was captured via video recording and analysed qualitatively. Results: Seventeen people with ID participated; females comprised 65%. At baseline, no participants correctly used any device. Pressurised metered dose inhalers, with or without accessory devices, were the most poorly used devices. Inhalation steps were poorly performed across all devices. Following training, the proportions of assessed participants that were able to master inhaler technique were 100% of Accuhaler users, 40% of Turbuhaler users, 25% of pressurised metered dose inhaler users and 0% of Handihaler users. Barriers identified included poor comprehension of breathing processes, the lack of attentiveness and poor dexterity. Facilitators for educator delivery of inhaler technique education included the use of analogies and being patient. Conclusions: This is the first study to examine inhaler technique mastery in people with ID. Results show that with education that addresses the unique patient barriers inherent in this group, some individuals can be trained to mastery. Structured modules of inhaler technique training tailored for people with ID, but which can be individualised, are recommended.     

Biallelic HERC1 mutations in a syndromic form of overgrowth and intellectual disability

We report two Colombian siblings affected by overgrowth, intellectual disability and facial dysmorphism. Exome (via NGS) and Sanger sequencing revealed that biallelic sequence variants in a novel gene (HERC1) might be related to the disease pathogenesis. These results provide useful data for future genotype–phenotype correlations and for a molecular diagnosis of overgrowth.     

Psychometric evaluation of a Moroccan version of health assessment questionnaire for use in Moroccan patients with rheumatoid arthritis

Objective of the study is to test the reliability and validity of a translated version of health assessment questionnaire (HAQ) on Moroccan patients with rheumatoid arthritis (RA). We led a prospective study from July 2004 to September 2005. A total of 100 Moroccan patients were recruited. After translation to dialect Arabic, back translation, expert committee review and pretesting of the questionnaire, it was administered to the selected patients and tested for construct validity, reliability and internal consistency. The construct validity was evaluated by correlating the yield of the questionnaire with other disease activity and severity parameters. The questionnaire was administered again after a time interval of between 2 and 10 days for evaluation of the reliability of this test. All the items were tested for their loyalty to the principal component. The adapted questionnaire showed a good internal consistency. Cronbach's alpha test was 0.994. The test-retest showed a strong reliability with a kappa test ranging from 0.70 to 0.92 for all domains. Intraclass correlation coefficient for the total score was 0.987. The Moroccan HAQ showed a strong validity. It correlates significantly with disease activity and severity parameters. The unidimentionality has been demonstrated. About 71.5% of all variabilities was accounted for by the first principal component. The Moroccan Arabic dialect version of HAQ is a reliable and valid instrument that can be self-administered by Moroccan RA patients to assess their functional disability.     

Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study

OBJECTIVE—To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function.
METHODS—During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis.
RESULTS—The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women).
CONCLUSIONS—Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability.

Keywords: osteoarthritis; hip; knee; locomotor disability