Medicine & Health

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  • (2021) Chiu, Vincent
    Primary liver cancer is characterised by poor prognosis, growing disease burden and propensity to develop on a background of chronic liver injury. Delivery of oncogene expression plasmids by hydrodynamic tail vein injection (HTVI) is an emergent method of modelling liver cancer, but does not reproduce chronic injury and fibrosis typical in human liver cancer. Injury and fibrosis contribute to the pathogenesis of liver cancer, although this is not well characterised in plasmid-HTVI liver cancer models. Two previously published plasmid-HTVI models (SB/AKT/c-Met, SB/AKT/NRas) were combined with the hepatotoxin thioacetamide (TAA) to induce liver injury. Consistent with previous characterisation, SB/AKT/c-Met developed steatosis with hepatocellular tumours, while SB/AKT/NRas developed steatosis with both hepatocellular and cholangiocellular tumours. TAA did not increase tumour burden but altered the phenotype of surrounding tissue. TAA reduced plasmid-induced steatosis and increased inflammatory cells and fibrosis with different morphology to TAA alone. In order to find novel gene expression and pathways associated with the cancer-injury combination, liver tissue was subject to whole transcriptome sequencing. Metabolism, inflammation, cell cycling and proliferative signalling pathways were among those that differed by either cancer or injury alone. The cancer-injury combinations had gene expression profiles distinct from cancer or injury alone, with a few differentially expressed genes not explained by either cancer or injury alone. In cancer-injury combinations, some pathways were synergistically upregulated but in many cases cancer and injury were antagonistic. Lipid and xenobiotic metabolism were novel pathways uniquely activated in the cancer-injury combinations. Selected genes were validated by conventional gene expression assays and immunohistochemistry. By characterising a plasmid-HTVI model with concomitant liver injury and fibrosis, it was found that liver injury did not accelerate or increase tumorigenesis but altered the phenotype and transcriptomic profile of the cancer models. In some cases, injury and oncogenes antagonised each other with respect to cancer-associated processes such as fibrosis and steatosis. Novel genes and pathways associated with the cancer-injury combination give insight into how chronic injury interacts with liver cancer in humans.

  • (2022) O'Hagan, Edel
    Low back pain is common and burdensome. The economic burden of low back pain in Australia includes total costs that exceed A$8 billion per year, costs which are projected to increase by 60% over the next 10 years. Less is known about the personal burden of low back pain. The first-line treatment consistently recommended for people with low back pain is patient education and advice. Regardless of the duration of low back pain, clinicians should provide advice to remain active, education on the benign nature of low back pain, and reassurance about the absence of a serious medical condition. Little guidance is available on how best this can be achieved. New treatments are urgently required to stem the rising costs of low back pain. Two proposed strategies are repurposing medicines, such as sleep medicines and media campaigns to target unhelp behaviours and beliefs. The overarching aim of this thesis was to investigate the personal burden of low back pain, evaluate attitudes toward education and advice for low back pain and explore contemporary options for managing low back pain. The methods used included qualitative content analysis, an observational study, development and evaluation of a new measurement tool, a systematic review and a randomised controlled trial. People with and without low back pain, online and in-person were recruited to participate across the five studies. The findings from each study are presented in individual chapters. The evidence in this thesis provides a scientific basis for understanding the personal burden of low back pain. The results describe how evaluating attitude toward education and advice could enable clinicians to tailor the patient education and advice they provide. Specific messages of reassurance rather than information about staying active should be prioritised. The Attitude toward Education and advice for Low back pain Questionnaire (AxEL-Q) is a valid and reliable tool to provide clinicians with an insight into attitudes toward education and advice at the outset of a clinical encounter. Sleep medicines should be further investigated before being endorsed to reduce pain intensity in people with acute low back pain. Social media and digital health interventions such as conversational agents provide options for supplementing low back pain management in the future.