Protocol for Fit Bodies, Fine Minds: a randomized controlled trial on the affect of exercise and cognitive training on cognitive functioning in older adults

Background. Declines in cognitive functioning are a normal part of aging that can affect daily functioning and quality of life. This study will examine the impact of an exercise training program, and a combined exercise and cognitive training program, on the cognitive and physical functioning of older adults. Methods/Design. Fit Bodies, Fine Minds is a randomized, controlled trial. Community-dwelling adults, aged between 65 and 75 years, are randomly allocated to one of three groups for 16 weeks. The exercise-only group do three 60-minute exercise sessions per week. The exercise and cognitive training group do two 60-minute exercise sessions and one 60-minute cognitive training session per week. A no-training control group is contacted every 4 weeks. Measures of cognitive functioning, physical fitness and psychological well-being are taken at baseline (0 weeks), post-test (16 weeks) and 6-month follop (40 weeks). Qualitative responses to the program are taken at post-test. Discussion. With an increasingly aged population, interventions to improve the functioning and quality of life of older adults are particularly important. Exercise training, either alone or in combination with cognitive training, may be an effective means of optimizing cognitive functioning in older adults. This study will add to the growing evidence base on the effectiveness of these interventions. Trial Registration. Australian Clinical Trials Register: ACTRN012607000151437

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

Risk of emergency hospitalisation and survival outcomes following adjuvant chemotherapy for early breast cancer in New South Wales, Australia

© 2019 John Wiley & Sons Ltd Objective: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. Methods: Linked data from New South Wales population-based and clinical cancer registries (2008–2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan–Meier and Cox proportional hazards methods. Results: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24–2.37 and OR 1.47, 95% CI 1.17–1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7–93.8) and were not hospitalised (93.1%, 95% CI 92.1–94.1). Conclusion: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety

Free Radicals and Human Aging Muscle

Aging is an inevitable biological process, characterized by a general decline in physiological and biochemical functions of the major systems. In the case of the 24 neuromuscular system, reductions in strength and mobility cause a deterioration 25 in motor performance, impaired mobility, and disability. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in accumulation of reactive oxygen species (ROS). As the level of oxidative stress 28 in skeletal muscle increases with age, age process is characterized by an imbalance between an increase in ROS production in the organism and antiox- idant defenses as a whole. The goal of this chapter is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account (I) different physiological factors, such as sex, fiber composition, muscle type, and function; (II) biochemical alterations in muscle induced by ROS; and (III) oxidative stress markers related to aged muscle, particularly 8-hydroxy-20-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and levels of carbonyl residues such as in Carbonyl Proteins (PC). Finally, we analyze data, present in literature, regarding the beneficial effects of nutrition and physical activity in preventing oxidative damages associated with sarcopenia