Clinical medicine (London, England)
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Alcoholic liver disease (ALD) and, increasingly, non-alcoholic fatty liver disease (NAFLD) are common causes of advanced liver disease in many developed countries including the UK. Both diseases share parallel natural histories, progressing from steatosis, to steatohepatitis and fibrosis/cirrhosis; and are characterised by substantial interindividual variation in disease outcome. This article will provide an overview of disease mechanisms, genetic modifiers and management, focusing principally on NAFLD, while drawing parallels between the two conditions where appropriate.
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Sarcopenia and frailty are important conditions that become increasingly prevalent with age. Sarcopenia is the loss of muscle mass and function, and frailty can be defined as multi-system impairment associated with increased vulnerability to stressors. There is overlap between the two conditions, especially in terms of the physical aspects of the frailty phenotype: low grip strength, gait speed and muscle mass. ⋯ In terms of intervention, there is evidence for the benefit of resistance exercise programmes, although these may not always be feasible. Considerable research into the use of medicines, both existing and new, as well as dietary supplements is ongoing. Finally in order to prevent or delay the development of these conditions, an additional approach is to consider aetiological factors operating across the life course.
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Multidrug-resistant tuberculosis (MDR TB) is a significant threat to global health estimated to account for nearly half a million new cases and over 200,000 deaths in 2013. The number of MDR TB cases in the UK has risen over the last 15 years, with ever more complex clinical cases and associated challenging public health and societal implications. In this review, we provide an overview of the epidemiology of MDR TB globally and in the UK, outline the clinical management of MDR TB and summarise recent advances in diagnostics and prospects for new treatment.
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There is a growing understanding of the epigenetic mechanisms that regulate gene expression in healthy conditions and a realisation that dysregulation of these mechanisms is an underlying factor in many human diseases. We discuss studies demonstrating that small molecule inhibitors of epigenetic regulatory proteins can block pathogenic mechanisms associated with rheumatoid arthritis, focusing on the effects of these inhibitors on synovial fibroblasts-fibroblast-like synoviocytes.
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Systemic sclerosis is the most severe disease within the scleroderma spectrum and is a major medical challenge with high mortality and morbidity. There have been advances in understanding of pathogenesis that reflect the interplay between immune-inflammatory processes and vasculopathy and fibrosis. ⋯ Treatment is available for many aspects of the disease although the available therapies are not curative and some complications remain very challenging, especially non-lethal manifestations such as fatigue, calcinosis and anorectal dysfunction. Immunosuppression is now established as a beneficial approach but balancing risk and benefit is vital, especially for powerful approaches such as autologous stem cell transplantation.