Abstract: Physical exercise is considered to be one of the beneficial factors of a proper lifestyle and is nowadays seen as an indispensable element for good health, able to lower the risk of disorders of the cardiovascular, endocrine and osteomuscular apparatus, immune system diseases and the onset of potential neoplasms. A moderate and programmed physical exercise has often been reported to be therapeutic both in the adulthood and in aging, since capable to promote fitness. Regular exercise alleviates the negative effects caused by free radicals and offers many health benefits, including reduced risk of all-cause mortality, sarcopenia in the skeletal muscle, chronic disease, and premature death in elderly people. However, physical performance is also known to induce oxidative stress, inflammation, and muscle fatigue. Many efforts have been carried out to identify micronutrients and natural compounds, also known as nutraceuticals, able to prevent or attenuate the exercise-induced oxidative stress and inflammation. The aim of this review is to discuss the benefits deriving from a constant physical activity and by the intake of antioxidant compounds to protect the body from oxidative stress. The attention will be focused mainly on three natural antioxidants, which are quercetin, resveratrol and curcumin. Their properties and activity will be described, as well as their benefits on physical activity and on aging, which is expected to increase through the years and can get favorable benefits from a constant exercise activity.

Abstract: Physical exercise has beneficial effects on metabolic diseases, and a combined therapeutic regimen of regular exercise and pharmaceutical treatment is often recommended for their clinical management. However, the mechanisms by which exercise produces these beneficial effects are not fully understood. Myokines, a group of skeletal muscle (SkM) derived peptides may play an important part in this process. Myokines are produced, expressed and released by muscle fibers under contraction and exert both local and pleiotropic effects. Myokines such as IL-6, IL-10, and IL-1ra released during physical exercise mediate its health benefits. Just as exercise seems to promote the myokine response, physical inactivity seems to impair it, and could be a mechanism to explain the association between sedentary behavior and many chronic diseases. Myokines help configure the immune-metabolic factor interface and the health promoting effects of physical exercise through the release of humoral factors capable of interacting with other tissues, mainly adipose tissue (AT). AT itself secretes proinflammatory cytokines (adipokines) as a result of physical inactivity and it is well recognized that AT inflammation can lead to the development of metabolic diseases, such as type 2 diabetes mellitus (T2DM) and atherosclerosis. On the other hand, the browning phenotype of AT has been suggested to be one of the mechanisms through which physical exercise improves body composition in overweight/obese individuals. Although, many cytokines are involved in the crosstalk between SkM and AT, in respect of these effects, it is IL-6, IL-15, irisin, and myostatin which seem to have the decisive role in this "conversation" between AT and SkM. This review article proposes to bring together the latest "state of the art" knowledge regarding Myokines and muscle-adipose tissue crosstalk. Furthermore, it is intended to particularly focus on the immune-metabolic changes from AT directly mediated by myokines.

Abstract: Animal research indicates that a combination of physical activity and sensory enrichment has the largest and the only sustaining effect on adult neuroplasticity. Dancing has been suggested as a human homologue to this combined intervention as it poses demands on both physical and cognitive functions. For the present exploratory study, we designed an especially challenging dance program in which our elderly participants constantly had to learn novel and increasingly difficult choreographies. This six-month-long program was compared to conventional fitness training matched for intensity. An extensive pre/post-assessment was performed on the 38 participants (63–80 y), covering general cognition, attention, memory, postural and cardio-respiratory performance, neurotrophic factors and–most crucially–structural MRI using an exploratory analysis. For analysis of MRI data, a new method of voxel-based morphometry (VBM) designed specifically for pairwise longitudinal group comparisons was employed. Both interventions increased physical fitness to the same extent. Pronounced differences were seen in the effects on brain volumes: Dancing compared to conventional fitness activity led to larger volume increases in more brain areas, including the cingulate cortex, insula, corpus callosum and sensorimotor cortex. Only dancing was associated with an increase in plasma BDNF levels. Regarding cognition, both groups improved in attention and spatial memory, but no significant group differences emerged. The latter finding may indicate that cognitive benefits may develop later and after structural brain changes have taken place. The present results recommend our challenging dance program as an effective measure to counteract detrimental effects of aging on the brain.

Abstract: In primary prevention, regular physical activity decreases the incidence of cardiovascular disease. At the endothelial level, this decreased incidence was attributed to higher expression and phosphorylation of the endothelial isoform of NO synthase, which results in a more effective radical

Abstract: Objective Exercise interventions benefit cancer patients. However, only low numbers of patients adhere to these interventions. This review aimed to identify predictors of exercise intervention adherence in patients with cancer, during and after multimodality cancer treatment. Methods A literature search was performed using electronic databases (PubMed, Embase, and Cochrane) to identify relevant papers published before February 1, 2017. Papers reporting randomized controlled trials, conducted in adult cancer patients who participated in an exercise intervention during and/or after multimodality cancer treatment, and providing outcome of factors predicting exercise adherence were included. Papers were assessed for methodological quality by using the Physiotherapy Evidence Database scale. Results The search identified 720 potentially relevant papers, of which 15 fulfilled the eligibility criteria. In these 15 studies, 2279 patients were included and 1383 of these patients were randomized to an exercise intervention. During cancer treatment, the factors predicting exercise adherence were as follows: location of the rehabilitation center, extensive exercise history, high motivation for exercise, and fewer exercise limitations. After cancer treatment, factors that predicted adherence were as follows: less extensive surgery, low alcohol consumption, high previous exercise adherence, family support, feedback by trainers, and knowledge and skills of exercise. Methodological quality of the included papers was rated "high". Conclusions The most prominent predictors of adherence to exercise interventions were location of the rehabilitation center, extensive exercise history, high motivation for exercise, and fewer exercise limitations. To increase the number of cancer patients who will benefit, these results should be considered into the development and implementation of future exercise interventions.

Abstract: There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients Exercise can be used in the treatment of several pain conditions, including However, what exact role exercise plays in migraine prevention is unclear Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective The review was based on a primary literature search on the PubMed using the search terms “migraine and exercise” Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency This is most likely due to an altered migraine triggering threshold in persons who exercise regularly However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers

Abstract: Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560.

Abstract: Background Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. Purpose To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Data sources Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Study selection Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Data extraction Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Data synthesis Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. Limitations The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Conclusions Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition.

Abstract: Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

Abstract: Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal—Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial. Trial registration number NCT02330926.

Abstract: Introduction Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naive for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant’s fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. Trial registration number NCT02730338.

Abstract: Animal models of exercise and Parkinson’s disease (PD) have found that the physiologic use of exercise may interact with the neurodegenerative disease process, likely mediated by brain derived neurotrophic factor (BDNF). No reviews so far have assessed the methodologic quality of available intervention studies or have bundled the effect sizes of individual studies on exercise-induced effects on BDNF blood levels in human PD. We searched MEDLINE, EMBASE, Cochrane Library, PsycINFO and PubMed from inception to June 2017. Data aggregated from two randomized controlled trials and four pre-experimental studies with a total of 100 ambulatory patients with idiopathic PD (Hoehn/Yahr ≤3) found improvements in BDNF blood concentration levels in all 6 studies (two RCTs and 4 pre-experimental studies). Pooled BDNF level change scores from the 2 RCTs resulted in a significant homogeneous summary effect size (Standardized Mean Difference 2.06, 95% CI 1.36 to 2.76), and a significant heterogeneous SES for the motor part of the UPDRS-III examination (MD -5.53, 95% CI -10.42 to -0.64). Clinical improvements were noted in all studies using a variety of outcome measures. The evidence-base consists primarily of small studies with low to moderate methodological quality. This review provides preliminary evidence for the effectiveness of physical exercise treatments for persons with PD on BDNF blood levels. Further research is needed.

Abstract: The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient group. A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed. 11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL. The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.

Abstract: Physical exercise is effective for sarcopenic elderly but evidence for the most effective mode of exercise is conflicting. The objective of this study was to investigate the effects of a three-month group-based versus home-based exercise program on muscular, functional/physical performance and quality of life (QoL) across elderly with sarcopenia. 54 elderly (47 women, 7 men aged 72.87 ± 7 years) were randomly assigned to one of three interventions: supervised group (n = 18), individualized home-based exercise (n = 18) and control group (n = 18). Body composition was determined by bioelectrical impedance analysis, calf measurement with inelastic tape and strength assessments (grip and knee muscle strength) via hand-held and isokinetic dynamometers. Functional assessments included four-meter (4 m), Τimed-Up and Go (TUG) and chair stand (CS) tests. QoL was assessed with Greek Sarcopenia Quality of Life (SarQol_GR) questionnaire. Outcomes were assessed at baseline, immediately post-intervention (week 12), and 3 months post-intervention (week 24). Significant group x time interactions (p < 0.001) were observed in QoL, calf circumference, TUG, CS, and 4 m tests, grip and knee muscle strength. Group-based compared to home-based exercise yielded significant improvements (p < 0.05) in muscle mass index, CS and 4 m tests, calf circumference, muscle strength at 12 weeks. Most improvements at 24 weeks were reported with grouped exercise. No changes were found across the control group. Results suggest group-based exercise was more effective than home-based for improving functional performance.

Abstract: Background: Aging is characterized with immunosenescence associated with a hyper-inflammatory state, characterized by elevated circulating levels of pro-inflammatory mediators. Physical exercise is a potential strategy for improving the immune system dysfunction and chronic inflammation that accompanies aging. However, there is a need to differentiate between aerobic and resistance exercise training regarding human immune system and systemic inflammation among the elderly Saudi population. Objective: The aim of this study was to compare the impact of 6 months of aerobic versus resisted exercise training on inflammatory cytokines and immune system response among elderly. Material and methods: Sixty previously sedentary elderly subjects participated in this study, their age ranged from 61- 66 years. All Subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=40) or resistance exercise group (group B, n=40). Number of CD3+,CD4+,CD8+ T cells count and CD4/CD8 ratio were quantified, IL-6, TNF-α and IL10 were measured before and after 6 months, at the end of the study. Results: The mean values of CD3+, CD4+ and CD8+ T cells count and IL-10 were significantly increased, whereas the mean values of CD4/CD8 ratio,IL-6 and TNF-α were significantly decreased in group (A) and group (B). Also; there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. Conclusion: The current study provides evidence that aerobic exercise is more appropriate in modulating the immune system and inflammatory markers among the elderly population. Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging.

Abstract: OBJECTIVES Dementia interferes with older adults' functioning in cognitive, daily, psychosocial, and neuroendocrine domains. The present study examined the psychophysiological effects of dance movement therapy (DMT) and physical exercise for older adults with dementia. METHODS This randomized controlled trial recruited 204 older adults diagnosed with mild dementia into the DMT, exercise, or waitlist control group. Both DMT and exercise interventions had similar intensity and comprised 24 hr of intervention that spanned over 12 weeks. All participants completed self-report questionnaires on psychosocial well-being, daily functioning, neurocognitive assessments, and salivary cortisol measures at baseline and 3 follow-up measurements more than 1 year. RESULTS The DMT group showed significant decreases in depression, loneliness, and negative mood (d = 0.33-0.42, p < .05) and improved daily functioning (d = 0.40, p < .01) and diurnal cortisol slope (d = 0.30, p < .01). The effects on daily functioning and cortisol slope remained at 1-year follow-up. The exercise group of matched intensity showed no significant effects on the outcomes. DISCUSSION The study findings support the potential utility of DMT as a multifaceted intervention for improving various aspects of functioning in older adults with declining cognitive abilities. The lack of beneficial effects for our exercise intervention and long-term DMT effects highlights the need to maintain persistent levels of exercise with adequate intensity and duration.

Abstract: MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in the regulation of physiological processes, such as adaptation to physical exercise, and also in disease settings, such as systemic arterial hypertension (SAH), type 2 diabetes mellitus (T2D), and obesity. In SAH, microRNAs play a significant role in the regulation of key signaling pathways that lead to the hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, proliferation, and phenotypic change in smooth muscle cells, and the hyperactivation of the sympathetic nervous system. MicroRNAs are also involved in the regulation of insulin signaling and blood glucose levels in T2D, and participate in lipid metabolism, adipogenesis, and adipocyte differentiation in obesity, with specific microRNA signatures involved in the pathogenesis of each disease. Many studies report the benefits promoted by exercise training in cardiovascular diseases by reducing blood pressure, glucose levels, and improving insulin signaling and lipid metabolism. The molecular mechanisms involved, however, remain poorly understood, especially regarding the participation of microRNAs in these processes. This review aimed to highlight microRNAs already known to be associated with SAH, T2D, and obesity, as well as their possible regulation by exercise training.

Abstract: Background National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. Objective The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD. Methods This study is a critical review of the literature. Results The progressive death of dopaminergic neurons in the substantia nigra is described as one of the main physiological mechanisms manifested before PD, directly interfering with motor behavior. However, PD is not only related to motor symptoms, but also to cognitive, autonomic, and mood impairments. Such effects may be attenuated by pharmacological influence, but also evidence suggests that the implementation of regular physical exercise programs may exhibit potential benefits over PD. The synthesis and expression of monoaminergic neurotransmitters can act positively on motor disorders, as well as directly or indirectly influence the neuronal plasticity of the brain, restoring neuronal pathways previously affected. Conclusion Physical exercise contributes effectively to the treatment of PD, and can play a preventive and maintenance role of physical fitness and mental health.

Abstract: Accumulating evidence indicates that exercise can improve learning and memory as well as attenuate neurodegeneration, including Alzheimer's disease (AD). In addition to improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates systems like angiogenesis and glial activation that are known to support neuroplasticity. Moreover, exercise helps to maintain a cerebral microenvironment that facilitates synaptic plasticity by enhancing the clearance of Aβ, one of the main culprits of AD pathogenesis. The purpose of this review is to highlight the positive impacts of exercise on promoting neuroplasticity. Possible mechanisms involved in exercise-modulated neuroplasticity are also discussed. Undoubtedly, more studies are needed to design an optimal personalized exercise protocol for enhancing brain function.