Clinical medicine (London, England)
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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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Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. ⋯ Future developments of novel therapies for obese women with PCOS should focus on promotion of weight loss and improvement in insulin sensitivity. In this context, therapies that complement lifestyle changes such as dietary modification and exercise, particularly during the maintenance phase of weight loss are important. Putative novel targets for therapy in PCOS include human brown adipose tissue.
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Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes.
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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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Since the advent of modern molecular tools, researchers have extensively shown that essential cellular machineries have robust circadian (roughly 24 hours) variations in their pace. This molecular rhythmicity translates directly into time-of-day-dependent variation in physiology in most organ systems, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. ⋯ Therefore, it has not been clear how physicians should incorporate knowledge of natural 24-hour rhythms into routine practice. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction that highlights new evidence for the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease.