Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study

Although leprosy has become a neglected disease, it is an important cause of disability, and 250,000 new cases are still diagnosed worldwide every year. The current study was carried out in Brazil, where almost 40,000 new cases of leprosy are diagnosed every year. The study targeted contacts of leprosy patients, who are at the highest risk of contracting the disease. We studied 2,135 contacts who were diagnosed at the Leprosy Outpatient Clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, RJ, Brazil, between 1987 and 2007. The presence of antibodies against a specific Mycobacterium leprae antigen (PGL-I) at the first examination and BCG vaccination status were evaluated. PGL-I-positive contacts had a higher risk of developing leprosy than PGL-I-negative contacts. Among the former, vaccinated contacts were at higher risk than unvaccinated contacts. Our results indicate that contact examination combined with PGL-I testing and BCG vaccination appears to justify the targeting of PGL-I-positive individuals for enhanced surveillance. Furthermore, it is highly recommended that PGL-I-positive contacts and contacts with a high familial bacterial index (i.e., the sum of results from index and co-prevalent cases), regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis

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

A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain

Validation and psychometric properties of the commitment to hip protectors (C-HiP) index in long-term care providers of British Columbia, Canada: a cross-sectional survey

Abstract Background If worn during a fall, hip protectors substantially reduce risk for hip fracture. However, a major barrier to their clinical efficacy is poor user adherence. In long-term care, adherence likely depends on how committed care providers are to hip protectors, but empirical evidence is lacking due to the absence of a psychometrically valid assessment tool. Methods We conducted a cross-sectional survey in a convenience sample of 529 paid care providers. We developed the 15-item C-HiP Index to measure commitment, comprised of three subscales: affective, cognitive and behavioural. Responses were subjected to hierarchical factor analysis and internal consistency testing. Eleven experts rated the relevance and clarity of items on 4-point Likert scales. We performed simple linear regression to determine whether C-HiP Index scores were positively related to the question, “Do you think of yourself as a champion of hip protectors”, rated on a 5-point Likert scale. We examined whether the C-HiP Index could differentiate respondents: (i) who were aware of a protected fall causing hip fracture from those who were unaware; (ii) who agreed in the existence of a champion of hip protectors within their home from those who didn’t. Results Hierarchical factor analysis yielded two lower-order factors and a single higher-order factor, representing the overarching concept of commitment to hip protectors. Items from affective and cognitive subscales loaded highest on the first lower-order factor, while items from the behavioural subscale loaded highest on the second. We eliminated one item due to low factor matrix coefficients, and poor expert evaluation. The C-HiP Index had a Cronbach’s alpha of 0.96. A one-unit increase in championing was associated with a 5.2-point (p < 0.01) increase in C-HiP Index score. Median C-HiP Index scores were 4.3-points lower (p < 0.01) among respondents aware of a protected fall causing hip fracture, and 7.0-points higher (p < 0.01) among respondents who agreed in the existence of a champion of hip protectors within their home. Conclusions We offer evidence of the psychometric properties of the C-HiP Index. The development of a valid and reliable assessment tool is crucial to understanding the factors that govern adherence to hip protectors in long-term care