The conserved lymphokine element 0 is a powerful activator and target for corticosteroid inhibition in human interleukin-5 transcription

The role of eosinophilia in allergic disorders indicates hIL-5 as a potential target for therapy. The conservation of hIL-5 gene proximal elements suggests they are important in controlling expression. Corticosteroids are important in the treatment of allergy, and are powerful inhibitors of IL-5 expression. This study aimed at understanding the role of hIL-5 conserved proximal elements, and elucidating the target of corticosteroid activity, in hIL-5 gene expression. Methods used include transient transfection of PBMC and PER117 cells with hIL-5 deletion constructs, EMSA, Western Blotting, and RT-PCR.

The conserved proximal CLE0/TATA elements driving a reporter gene gave similar or higher expression than a 500 bp promoter in primary human T cells and a T-cell line. Two and three copies of IL-5 CLE0 upstream of the silent IL-4 minimal promoter gave 30–45 fold increases in expression in forward orientation, but little activity in reverse orientation. Consequently, CLE0 is a powerful activator but not a classical enhancer. Deletion analysis identified CLE0 as the key element in the inhibition of IL-5 reporter constructs by dexamethasone, and RT-PCR analysis indicated that GILZ expression correlated with dexamethasone-induced inhibition of IL-5. Ectopic expression of GILZ, confirmed by western blotting, gave a 90% inhibition of promoter constructs in absence of dexamethasone. CLE0 is a powerful activator sufficient for the inducible expression of IL-5, and functions when moved upstream in a heterologous promoter. CLE0 is also the main target for IL-5 inhibition by dexamethasone, and we present evidence consistent with a role of GILZ in this.     

Impact of Non-HIV Related Comorbidities on Retention in HIV Medical Care: Does Retention Improve Over Time?

The purpose of this study was to understand how the presence of comorbid conditions affects retention in HIV medical care over time. A retrospective cohort design employing a medical chart review was conducted. A generalized linear mixed model was used to determine the predictors that affect retention over time. The mean follow-up for the study population was 5.75 years, and only 48.6 % achieved optimal retention. During the study period, 882 non-HIV related comorbidities were diagnosed in 610 (44.9 %) patients of whom, approximately 31 % had ≥2 comorbidities diagnosed. In the mixed model, the number of comorbidities diagnosed during the study period was associated with improved retention over time (odds ratio = 2.28; 95 % confidence interval = 1.83–2.71). Having a non-HIV related comorbid condition was associated with improved retention, while those patients who were ‘healthier’ had worse retention. More research is needed to identify factors that improve retention and to quantify the impact of these factors.     

Psychological distress and related work attendance among small-to-medium enterprise owner/managers: literature review and research agenda

Small-to-medium enterprises (SMEs) may experience the antecedents and consequences of depression more acutely than larger organizations. Managing depression-related sickness absenteeism and presenteeism, and associated productivity loss may also be more challenging because the SME's size and structure make administration, finance, and responsibilities of human resources difficult. This may diminish the growth and long-term sustainability of SME. However, the mental health of the SME workforce is a neglected sector in occupational health research and practice, despite the contribution it makes to developed economies worldwide. This study aims to review the literature on current stress, burnout, and depression, and uses existing knowledge of SME structure and characteristics to propose a theory as to why this may be the case. Further, using the information garnered, it developed a model to guide future research designed to test these assumptions, and inform the development of workplace mental health promotion programmes tailored to the needs of the SME sector.