The long-term benefits of a multi-component exercise intervention to balance and mobility in healthy older adults

We examined the long-term effects of a multi-component exercise program on balance, mobility and exercise behavior. The benefits of a community-based resistance and flexibility exercise intervention in a group of healthy older (60-75 years) individuals were recorded 12 months after completion of the randomized control intervention. Differences between those participants who continued to exercise and those who discontinued were investigated. Significant improvements from baseline in sit to stand (p < 0.001), timed up and go (p = 0.001), and sway (p < 0.001) remained at follow up in the exercise intervention group, with a control group unchanged. Participants who continued exercising had significantly greater improvements in strength immediately after the intervention, compared to those who discontinued (p = 0.004). Those who continued regular resistance training performed better in the step test at 12-month follow up (p = 0.009) and believed that the program was of more benefit to their physical activity (p < 0.001) than those who discontinued exercising. Benefits to balance and mobility persist 1 year after participation in a multi-component exercise program, due in part to some continuing participation in resistance training. Motivation to continue resistance training may be related real and perceived benefits attained from the intervention as well as the environmental context of the intervention.     

Translational paradigms in pharmacology and drug discovery

The translational sciences represent the core element in enabling and utilizing the output from the biomedical sciences and to improving drug discovery metrics by reducing the attrition rate as compounds move from preclinical research to clinical proof of concept. Key to understanding the basis of disease causality and to developing therapeutics is an ability to accurately diagnose the disease and to identify and develop safe and effective therapeutics for its treatment. The former requires validated biomarkers and the latter, qualified targets. Progress has been hampered by semantic issues, specifically those that define the end product, and by scientific issues that include data reliability, an overt reductionistic cultural focus and a lack of hierarchically integrated data gathering and systematic analysis. A necessary framework for these activities is represented by the discipline of pharmacology, efforts and training in which require recognition and revitalization.     

Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling

DNA methylation plays an important role in cancer biology and methylation events are important prognostic and predictive markers in many tumor types. We have used methylation-specific multiplex ligation-dependent probe amplification to survey the methylation status of MGMT and 25 tumor suppressor genes in 73 glioblastoma cases. The data obtained was correlated with overall survival and response to treatment. The study revealed that methylation of promoter regions in TP73 (seven patients), THBS1 (eight patients) and PYCARD (nine patients) was associated with improved outcome, whereas GATA5 (21 patients) and WT1 (24 patients) promoter methylation were associated with poor outcome. In patients treated with temozolomide and radiation MGMT and PYCARD promoter methylation events remained associated with improved survival whereas GATA5 was associated with a poor outcome. The identification of GATA5 promoter methylation in glioblastoma has not previously been reported. Furthermore, a cumulative methylation score separated patients into survival groups better than any single methylation event. In conclusion, we have identified specific methylation events associated with patient outcome and treatment response in glioblastoma, and these may be of functional and predictive/prognostic significance. This study therefore provides novel candidates and approaches for future prospective validation.