Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis.

The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27(+) but not HLA-B27(-) AS patients or controls. Forty-nine AS cases and 22 healthy controls were grouped according to HLA-B27 status and AS-associated ERAP1 rs30187 genotypes: HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective), HLA-B27(-)ERAP1(risk) and HLA-B27(-)ERAP1(protective). Expression levels of ER-stress markers GRP78 (8 kDa glucose-regulated protein), CHOP (C/EBP-homologous protein) and inflammatory cytokines were determined in peripheral blood mononuclear cell and ileal biopsies. We found no differences in ER-stress gene expression between HLA-B27(+) and HLA-B27(-) cases or healthy controls, or between cases or controls stratified by carriage of ERAP1 risk or protective alleles in the presence or absence of HLA-B27. No differences were observed between expression of IL17A or TNF (tumour necrosis factor) in HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective) and HLA-B27(-)ERAP1(protective) cases. These data demonstrate that aberrant ERAP1 activity and HLA-B27 carriage does not alter ER-stress levels in AS, suggesting that ERAP1 and HLA-B27 may influence disease susceptibility through other mechanisms.

Diversity of community acquired MRSA carrying the PVL gene in Queensland and New South Wales, Australia.

Emergence and dissemination of community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strains are being reported with increasing frequency in Australia and worldwide. These strains of CA-MRSA are genetically diverse and distinct in Australia. Genotyping of CA-MRSA using eight highly-discriminatory single nucleotide polymorphisms (SNPs) is a rapid and robust method for monitoring the dissemination of these strains in the community. In this study, a SNP genotyping method was used to investigate the molecular epidemiology of 249 community acquired non-multiresistant MRSA (nm-MRSA) isolates over a 12-month period from routine diagnostic specimens. A real-time PCR for the presence of Panton-Valentine leukocidin (PVL) was also performed on these isolates. The CA-MRSA isolates were sourced from a large private laboratory in Brisbane, Australia that serves a wide geographic region encompassing Queensland and Northern New South Wales. This study identified 16 different STs and 98% of the CA-MRSA isolates were positive for the PVL gene. The most common ST was ST93 with 41% of isolates testing positive for this clone.

The relationship of self-efficacy expectancies to relapse among alcohol dependent men and women: a prospective study.

OBJECTIVE: We studied the relationship of self-efficacy expectancies measured during inpatient alcohol treatment and time to first drink and time to relapse following hospitalization. We also examined whether the relationship of in-hospital self-efficacy and posttreatment drinking outcome differed by gender. METHOD: We measured self-efficacy expectancies using the Situational Confidence Questionnaire (SCQ) in 100 subjects (59 men) during inpatient treatment for alcohol dependence. We followed subjects monthly for 1 year and examined the relationship of their in-hospital SCQ scores to posttreatment drinking behavior, as measured by time to first drink, time to relapse and percent abstinent days. RESULTS: Self-efficacy during hospitalization was related to relapse during the 12 months following hospitalization. Survival analysis demonstrated that in-hospital SCQ scores greater than 45 were predictive of better drinking outcomes. The median number of days to relapse after treatment were 30 and 135, respectively, in those with in-hospital SCQ scores less than or equal to 45 compared with those with SCQ scores greater than 45. There were no gender differences in self-efficacy measured during hospitalization, nor were there gender differences in the relationship of self-efficacy to time to relapse. However, men with SCQ scores less than or equal to 45 had fewer abstinent days during follow-up. CONCLUSIONS: Among both men and women being treated for alcohol dependence, a cut-off score of 45 on the SCQ may be especially important in helping clinicians assess patients who are at high risk for more rapid return to drinking after hospitalization.