Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which is responsible for a significant proportion of alcohol-attributable deaths globally. Other than reducing alcohol consumption, there are currently no effective treatments for alcohol-related liver disease. Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants. It plays important roles in several aspects of alcohol-related liver disease pathogenesis. Here, we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P450 2E1 system producing reactive oxygen species, acetaldehyde and protein and DNA adducts. These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis. Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling. There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation. Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes. This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation. Improved understanding of these processes may identify novel targets for therapy.

This study adds to the growing body of research on scientist and practitioner interests by empirically examining temporal stability as a function of experiences gained through the successful completion of a doctoral-level scientist-practitioner model-based training program in school or counseling psychology. Twenty-six participants, who completed the paper-and-pencil version of the Scientist Practitioner Inventory between 1996 and 2002 at the beginning of their doctoral program, recently completed an online version of the same inventory to measure their preinterest and postinterest in scientist and practitioner domains. At the pretesting and posttesting stages, school and counseling psychology students differed significantly in terms of practitioner interests. For the combined groups, pretesting and posttesting revealed a significant decrease for the scientist domain but not for the practitioner domain. No significant change occurred between preinterests and postinterests for individuals in the scientist or practitioner domains for school psychology or counseling psychology majors when tested separately. Findings from this study support the notion that scientist and practitioner interests are fairly stable over time and across experiences gained through training and professional roles.

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AimsWe investigated whether we could have a material and sustained impact on immunology test ordering by primary care clinicians by building evidence-based and explanatory algorithms into test ordering software.MethodsA service evaluation revealed cases of over-requesting of antinuclear antibody, allergen-specific IgE and total IgE tests, and under-requesting of urine protein electrophoresis. We conducted a quality improvement programme to address this. We determined the most effective and efficient intervention would be to embed evidence-based and advice-based decision-support algorithms in the ordering software. Consultation with general practitioners revealed lack of knowledge and confidence about testing, and an appetite for support. We iteratively designed and implemented algorithms for the four sets of tests for the primary care practices in our catchment and made them available to other hospital trusts in our region. The ordering system now contains links to advice sheets for clinicians and their patients and to an email address for queries to the lab.ResultsWe observe large (36% to 88%) reductions in testing activity (workload) for the over-requested tests and large (28%–135%) increases for the under-requested test. We show that these changes are sustained. There have been no complaints from the clinicians and queries to the lab are now minimal (less than one per month on average).ConclusionsEmbedding algorithms in the ordering software can be acceptable to clinicians and have a major and sustained impact on overuse or underuse of tests. The algorithms can be replicated by other hospital trusts.