Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype

Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype–phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (p < 0.003) while. DRB1*03/*04 heterozygotes were under-represented (p < 0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB1*03/*01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM.     

Tobacco, Caffeine, Alcohol and Illicit Substance Use Among Consumers of a National Psychiatric Disability Support Service

Previous research has consistently documented high rates of tobacco smoking and substance use disorders among young people with serious mental illness. However, limited studies have been conducted outside traditional clinical settings. In an attempt to address this shortfall and to better understand the needs of young people accessing its services, a national psychiatric disability support service (Neami) examined the prevalence and impact of substance use among 120 consumers from across Australia aged 30?years and under. Results indicated extremely high rates of tobacco use, with 68% of participants identified as daily smokers. In addition, 33.4% met criteria for an alcohol use disorder, whilst 40.8% met criteria for a cannabis use disorder. Overall rates of other illicit substance use were low. This study reinforces the need for routine alcohol and drug screening and assessment across all mental health settings, as well as appropriate support strategies that address high level smoking and caffeine intake.     

Superparamagnetic iron oxide nanoparticles as a means to track mesenchymal stem cells in a large animal model of tendon injury

The goal of this study was to establish an SPIO‐based cell‐tracking method in an ovine model of tendonitis and to determine if this method may be useful for further study of cellular therapies in tendonitis in vivo. Functional assays were performed on labeled and unlabeled cells to ensure that no significant changes were induced by intracellular SPIOs. Following biosafety validation, tendon lesions were mechanically (n = 4) or chemically (n = 4) induced in four sheep and scanned ex vivo at 7 and 14 days to determine the presence and distribution of intralesional cells. Ovine MSCs labeled with 50 µg SPIOs/mL remained viable, proliferate, and undergo tri‐lineage differentiation (p < 0.05). Labeled ovine MSCs remained detectable in vitro in concentrated cell numbers as low as 10 000 and in volumetric distributions as low as 100 000 cells/mL. Cells remained detectable by MRI at 7 days, as confirmed by correlative histology for dually labeled SPIO+/GFP+ cells. Histological evidence at 14 days suggested that SPIO particles remained embedded in tissue, providing MRI signal, although cells were no longer present. SPIO labeling has proven to be an effective method for cell tracking for a large animal model of tendon injury for up to 7 days post‐injection. The data obtained in this study justify further investigation into the effects of MSC survival and migration on overall tendon healing and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.     

MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi

Lyme borreliosis, caused by the tick-borne bacterium Borrelia burgdorferi, has become the most common vector-borne disease in North America over the last three decades. To understand the dynamics of the epizootic spread and to predict the evolutionary trajectories of B. burgdorferi, accurate information on the population structure and the evolutionary relationships of the pathogen is crucial. We, therefore, developed a multilocus sequence typing (MLST) scheme for B. burgdorferi based on eight chromosomal housekeeping genes. We validated the MLST scheme on B. burgdorferi specimens from North America and Europe, comprising both cultured isolates and infected ticks. These data were compared with sequences for the commonly used genetic markers rrs-rrlA intergenic spacer (IGS) and the gene encoding the outer surface protein C (ospC). The study demonstrates that the concatenated sequences of the housekeeping genes of B. burgdorferi provide highly resolved phylogenetic signals and that the housekeeping genes evolve differently compared with the IGS locus and ospC. Using sequence data, the study reveals that North American and European populations of B. burgdorferi correspond to genetically distinct populations. Importantly, the MLST data suggest that B. burgdorferi originated in Europe rather than in North America as proposed previously.     

Consumer and staff perspectives of the implementation frequency and value of recovery and wellbeing oriented practices

Background

Despite advances in our understanding of what mental health systems and services can do to enhance recovery and wellbeing outcomes for people seeking support, there is limited evidence demonstrating that this body of work has translated successfully into mental health service practice. The Collaborative Recovery Model (CRM) is a practice framework that has been designed to support application of recovery and wellbeing oriented principles and practices within mental health service delivery. The aims of this study were to assess consumer and staff perceptions of implementation frequency during service engagement and the value of this approach for assisting recovery within a setting where the CRM approach had been adopted.

Methods

The setting was a large Australian community managed mental health organisation. The study involved a cross-sectional analysis of consumer (n?=?116) and staff practitioner (n?=?62) perspectives. A series of paired sample t-tests assessed for differences between consumer and staff perceptions of the: (i) importance of key practice elements for assisting recovery, and the (ii) frequency that key practice elements are utilised during engagement sessions. Spearman’s r correlational analysis explored associations between importance, frequency and helpfulness of sessions.

Results

Key practice elements of the model were applied during service interactions at a high level and perceived by the majority of consumers and staff participants as being important or very important for assisting recovery. Significant moderate correlations were found between the extent that practice elements were valued and the level at which they were applied. Higher levels of implementation of CRM practices were associated with higher ratings of perceived session helpfulness. The strongest association was between ‘encouragement to set tasks to complete between support visits’ and perceived helpfulness.

Conclusions

Consumer and staff responses revealed that the key practice elements of the CRM were frequently implemented during service engagement interactions and were seen as valuable for assisting recovery. The level of agreement between raters suggests firstly, that the key practice elements were apparent and able to be rated as occurring, and secondly that the CRM approach is seen as responsive to consumer needs. The results have implications for translating recovery and wellbeing oriented knowledge into mental health service practice.

     

Apolipoprotein epsilon alleles in sporadic inclusion body myositis: a reappraisal

Previous studies have differed as to whether APOE epsilon4 is a susceptibility factor for developing sporadic inclusion body myositis (sIBM), with a positive association being found only in an Australian cohort of cases. We have now re-examined this in a larger cohort of 57 sIBM cases and have also carried out a meta-analysis of all the published studies looking for evidence of a risk association or effect of APOE alleles on disease expression. Our findings argue against a specific role for any APOE alleles in conferring susceptibility to sIBM but have demonstrated a non-significant trend towards an earlier age-of-onset in patients with the epsilon2 allele.