Australian radiation therapy - Part Two: Reflections of the past, the present, the future

INTRODUCTION: Documentation on the history of Australian radiotherapy is limited. This study provides radiation therapists' (RTs) perspectives of the people, workplace, and work practices in Australian radiotherapy centres from 1960 onwards. It provides a follow-up to our previous study: Australian radiation therapy: An overview – Part one, which outlines the history and development of radiotherapy from conception until present day. METHODS: Four focus groups were conducted on separate occasions in 2010, one in South Australia and three in Victoria, Australia. Participants who worked in radiotherapy were purposively selected to ensure a range of experience, age, and years of work. RESULTS: From a RT perspective, radiotherapy has evolved from a physically demanding ‘hands-on’ work environment, often with unpleasant sights and smells of disease, to a more technology-driven workplace. CONCLUSION: Understanding these changes and their subsequent effects on the role of Australian RTs will assist future directions in advanced role development

Superantigens from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1beta.

Background: Staphylococcus aureus is one of the most common bacteria in human sepsis, a condition in which the activation of blood coagulation plays a critical pathophysiological role. During severe sepsis and septic shock microthrombi and multiorgan dysfunction are observed as a result of bacterial interference with the host defense and coagulation systems. Objectives: In the present study, staphylococcal superantigens were tested for their ability to induce procoagulant activity and tissue factor (TF) expression in human whole blood and in peripheral blood mononuclear cells. Methods and results: Determination of clotting time showed that enterotoxin A, B and toxic shock syndrome toxin 1 from S. aureus induce procoagulant activity in whole blood and in mononuclear cells. The procoagulant activity was dependent on the expression of TF in monocytes since antibodies to TF inhibited the effect of the toxins and TF was detected on the surface of monocytes by flow cytometry. In the supernatants from staphylococcal toxin-stimulated mononuclear cells, interleukin (IL)-1beta was detected by ELISA. Furthermore, the increased procoagulant activity and TF expression in monocytes induced by the staphylococcal toxins were inhibited in the presence of IL-1 receptor antagonist, a natural inhibitor of IL-1beta. Conclusions: The present study shows that superantigens from S. aureus activate the extrinsic coagulation pathway by inducing expression of TF in monocytes, and that the expression is mainly triggered by superantigen-induced IL-1beta release

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP

N/OFQ-NOP system in food intake

While lifestyle modifications should be the first-line actions in preventing and treating obesity and eating disorders, pharmacotherapy also provides a necessary tool for the management of these diseases. However, given the limitations of current anti-obesity drugs, innovative treatments that improve efficacy and safety are needed. Since the discovery that the activation of the Nociceptin/Orphanin (N/OFQ) FQ peptide (NOP) receptor by N/OFQ induces an increase of food intake in laboratory animals, and the finding that this effect can be blocked by NOP antagonists, many NOP agonists and antagonists have been synthesized and tested in vitro and in vivo for their potential regulation of feeding behavior. Promising results seem to suggest that the N/OFQergic system may be a potential therapeutic target for the neural control of feeding behavior and related pathologies, especially in binge-like eating behavior