Search

Chromatin-modifying drugs, such as histone deacetylase inhibitors (HDACi), have shown potential as cancer therapeutics, either alone or in combination with other therapies. HDACi have the ability to reverse aberrant epigenetic modifications associated with cancer, namely dysregulated histone acetylation. There are currently three FDA approved HDACi; vorinostat, romidepsin, and panobinostat. Epigenetic modifications can regulate the expression of protein coding genes, and in addition can alter expression of microRNA (miRNA) genes. Many miRNAs play key roles in cell proliferation and apoptosis, and are commonly dysregulated in cancer states. A number of in vitro and in vivo studies have demonstrated the ability of chromatin-modifying drugs to alter miRNA expression, which may provide the basis for further investigation of miRNAs as therapeutic targets or as biomarkers of drug response. This review summarises findings from studies investigating the effects of HDACi on miRNA expression, as well as key clinical trials involving HDACi. Understanding how chromatin-modifying drugs epigenetically modulate miRNA genes provides further insight into the cellular mechanisms that deliver therapeutic responses, and may assist in refining treatment strategies. Drug Dev Res 76 : 296-317, 2015. (c) 2015 Wiley Periodicals, Inc. Refereed/Peer-reviewed

Title: Conversational Disfluencies as a Predictor of Attention Problems in Preschool, Author: Elizabeth Hart, Location: Thode Attention Deficit Hyperactivity Disorder (ADHD) is frequently comorbid with language impairment. There is currently no detailed linguistic profile of children with ADHD. A previous study (Redmond, 2004) found that in conversation, children with ADHD produced more words per maze than typically developing controls, but did not determine the specific disfluency driving the correlation. The present study examined the conversational language, and measures of attention deficits, executive functioning and spatial intelligence of a non-clinical community sample of 46 preschool-aged children. The results replicated Redmond's finding and further indicated that attention deficits and executive dysfunctioning were associated with the production of more long repairs and restarts. The number of pauses was positively correlated with spatial abilities. Findings suggest that a preschooler who produces many long repairs and restarts should be monitored for possible attention deficits. Thesis Master of Science (MS)

Background Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. Methods and Design This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders. Discussion The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers. Trial registration Australian Clinical Trials Registry: ACTRN12607000017426.

Aim: To determine, in Australian chronic obstructive pulmonary disease (COPD) outpatients, the prevalence of nutritional depletion, adequacy of dietary intake and relationship between nutritional depletion and clinical indicators. Methods: Cross-sectional study of 66 stable COPD outpatients (mean forced expiratory volume in one second (FEV1) of 60% predicted (95% confidence interval 54, 67) ). Nutritional status was assessed using body mass index (BMI) and fat-free mass index (FFMI). Four-day estimated food records were compared with the new Australian Nutrient Reference Values. Clinical indicators included respiratory function and quality of life (QoL) using the St George Respiratory Questionnaire. Results: Thirty per cent of subjects (n = 20) were nutritionally depleted (BMI