Association of the CCR5 gene with juvenile idiopathic arthritis

The CC chemokine receptor 5 (CCR5) has been shown to be important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction. A 32 base-pair insertion/deletion variant (CCR5Δ32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Δ32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Δ32 is associated with JIA in an UK population. CCR5Δ32 was genotyped in JIA cases (n=1054) and healthy controls (n=3129) and genotype and allele frequencies were compared. A meta-analysis of our study combined with previously published studies was performed. CCR5Δ32 was significantly associated with protection from developing JIA, in this UK data set (P(trend)=0.006, odds ratio (OR) 0.79 95% confidence interval (95% CI): 0.66-0.94). The meta-analysis of all published case-control association studies confirmed the protective association with JIA (P=0.001 OR 0.82 95% CI: 0.73-0.93). CCR5Δ32 is a functional variant determining the number of receptors on the surface of T cells, and it is hypothesized that the level of CCR5 expression could influence the migration of proinflammatory T cells into the synovium and thus susceptibility to JIA

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Recent genetic studies have led to identification of numerous loci that are associated with susceptibility to autoimmune diseases. The strategy of using information from these studies has facilitated the identification of novel juvenile idiopathic arthritis (JIA) susceptibility loci, specifically, PTPN22 and IL2RA. Several novel autoimmune susceptibility loci have recently been identified, and we hypothesise that single-nucleotide polymorphisms (SNPs) within these genes may also be JIA susceptibility loci. Five SNPs within the genes AFF3, IL2/IL21, IL7R, CTLA4 and CD226, previously associated with multiple autoimmune diseases were genotyped, in a large data set of Caucasian JIA patients and controls, and tested for association with JIA. We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation. All results require validation in independent JIA data sets. Further characterisation of the specific causal variants will be required before functional studies can be performed

Get with the guidelines : management of chronic obstructive pulmonary disease in emergency departments in Europe and Australasia is sub-optimal

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non-invasive ventilation (NIV) for patients with respiratory acidosis. Aim: To determine compliance with guideline recommendations for patients treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. Methods: In each region, an observational prospective cohort study was performed that included patients presenting to ED with the main complaint of dyspnoea during three 72-h periods. This planned sub-study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in-hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. Results: A total of 801 patients was included from 122 ED (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44 and 60.6% of patients with pH Conclusion: Compliance with guideline recommended treatments, in particular administration of corticosteroids and NIV, was sub-optimal in both regions. Improved compliance has the potential to improve patient outcome.Peer reviewe

The association between sleep patterns and obesity in older adults.

BackgroundReduced sleep duration has been increasingly reported to predict obesity. However, timing and regularity of sleep may also be important. In this study, the cross-sectional association between objectively measured sleep patterns and obesity was assessed in two large cohorts of older individuals.MethodsWrist actigraphy was performed in 3053 men (mean age: 76.4 years) participating in the Osteoporotic Fractures in Men Study and 2985 women (mean age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and regularity of sleep patterns were assessed across nights, as well as daytime napping.ResultsGreater night-to-night variability in sleep duration and daytime napping were associated with obesity independent of mean nocturnal sleep duration in both men and women. Each 1 h increase in the standard deviation of nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47) among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence interval: 1.17-1.41) in women. In contrast, associations between later sleep timing and night-to-night variability in sleep timing with obesity were less consistent.ConclusionsIn both older men and women, variability in nightly sleep duration and daytime napping were associated with obesity, independent of mean sleep duration. These findings suggest that characteristics of sleep beyond mean sleep duration may have a role in weight homeostasis, highlighting the complex relationship between sleep and metabolism

Initiation and completion of treatment for latent tuberculosis infection in migrants globally:a systematic review and meta-analysis

BACKGROUND: Latent tuberculosis infection (LTBI) is one of the most prevalent infections globally and can lead to the development of active tuberculosis disease. In many low-burden countries, LTBI is concentrated within migrant populations often because of a higher disease burden in the migrant's country of origin. National programmes consequently focus on screening and treating LTBI in migrants to prevent future tuberculosis cases; however, how effective these programmes are is unclear. We aimed to assess LTBI treatment initiation and outcomes among migrants, and the factors that influence both. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, and Global Health, and manually searched grey literature from Jan 1, 2000, to April 21, 2020. We included primary research articles reporting on LTBI treatment initiation or completion, or both, in migrants and excluded articles in which data were not stratified by migrant status, or in which the data were related to outcomes before 2000. There were no geographical or language restrictions. All included studies were quality appraised using recognised tools depending on their design, and we assessed the heterogeneity of analyses using I2. We extracted data on the numbers of migrants initiating and completing treatment. Our primary outcomes were LTBI treatment initiation and completion in migrants (defined as foreign-born). We used random-effects meta-regression to examine the influence of factors related to these outcomes. The study is registered with PROSPERO (CRD42019140338). FINDINGS: 2199 publications were retrieved screened, after which 39 publications from 13 mostly high-income, low-burden countries were included in our analyses, with treatment initiation and completion data reported for 31 598 migrants positive for LTBI, with not all articles reporting the full pathway from initiation to completion. The pooled estimate for the true proportion of migrants testing positive who initiated treatment was 69% (95% CI 51-84; I2= 99·62%; 4409 of 8764). The pooled estimate for the true proportion of migrants on treatment in datasets, who subsequently completed it was 74% (95% CI = 66-81; I2= 99·19%; 15 516 of 25 629). Where data were provided for the entire treatment pathway, the pooled estimate for the true proportion of migrants who initiated and completed treatment after a positive test was only 52% (95% CI 40-64; I2= 98·90%; 3289 of 6652). Meta-regression showed that LTBI programmes are improving, with more recent reported data (2010-20) associated with better rates of treatment initiation and completion, with multiple complex factors affecting treatment outcomes in migrants. INTERPRETATION: Although our analysis highlights that LTBI treatment initiation and completion in migrants has improved considerably from 2010-20, there is still room for improvement, with drop out reported along the entire treatment pathway. The delivery of these screening and treatment programmes will require further strengthening if the targets to eradicate tuberculosis in low-incidence countries are to be met, with greater focus needed on engaging migrants more effectively in the clinic and understanding the diverse and unique barriers and facilitators to migrants initiating and completing treatment. FUNDING: European Society of Clinical Microbiology and Infectious Diseases, the Rosetrees Trust, the National Institute for Health Research, and the Academy of Medical Sciences

Optical and radio survey of Southern Compact Groups of galaxies. I. Pilot study of six groups

Multi-wavelength observations of Hickson's Compact Groups (HCGs) have shown that many of these groups are physical bound structures and are in different stage of evolution, from spiral-dominated systems to almost merged objects. Very few studies have analysed the Southern Compact Groups (SCGs) sample, which is though to be younger that HCGs, due to an on average higher number of spiral galaxies. We present here the first results from optical and radio observations on a pilot sample of SCGs.Comment: accepted on A&A on July 19, 2007. Figures 1 and 3-12 will be available only in electronic for

Group Mentoring: A Study of Mentoring Groups in Three Programs

In an effort to provide more youth with mentors, mentoring programs are implementing several promising new approaches. This report describes the strengths and challenges of group mentoring-an approach that is gaining popularity. Findings suggest that group mentoring is reaching youth and volunteers who are unlikely to participate in traditional one-on-one mentoring, and that the approach may provide youth with important benefits, especially the development of social skills. On the other hand, mentoring groups vary widely in their size, structure and focus, and in the extent to which they foster strong mentoring relationships and benefits for youth. Implications for the mentoring field and for future research are discussed