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Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders.
Nay, K, Smiles, WJ, Kaiser, J, McAloon, LM, Loh, K, Galic, S, Oakhill, JS, Gundlach, AL, Scott, JW
International journal of molecular sciences. 2021;22(8)
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Exercise as therapy for mental health disorders has become common due to its reported benefits and low cost. There are many biological ways in which exercise may help mood disorders and diseases associated with brain degeneration and this review article aimed to highlight these. The authors first highlighted the research indicating that exercise may be protective in mood disorders with studies showing reduction of symptoms of depression, anxiety, schizophrenia, autism, and bipolar disorder. Exercise may also be of benefit in several brain degenerative disorders with studies indicating a positive impact in individuals with Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Multiple Sclerosis. Studies have also indicated that individuals with brain injuries, such as stroke may also benefit. Several reasons for this were highlighted. When muscle is stimulated during exercise a key brain signalling molecule may be produced, known as brain-derived neurotrophic factor (BDNF). BDNF may have the effect of preventing brain degeneration and promoting regeneration. Exercise may also increase gut microbial diversity and increase beneficial bacteria which may benefit the brain in several ways. It was concluded that exercise may have beneficial effects for individuals with brain disorders. This study could be used by healthcare professionals to understand how exercise may be of benefit to individuals with mood disorders, brain degenerative diseases and brain injuries as part of a holistic treatment plan.
Abstract
As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle-brain, liver-brain and gut-brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise-brain communication and their benefits for physiology and brain function.
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The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.
Chan, RJ, Crichton, M, Crawford-Williams, F, Agbejule, OA, Yu, K, Hart, NH, de Abreu Alves, F, Ashbury, FD, Eng, L, Fitch, M, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2021;(12):1552-1570
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Abstract
BACKGROUND Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.
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Regulation of energy homeostasis by the NPY system.
Loh, K, Herzog, H, Shi, YC
Trends in endocrinology and metabolism: TEM. 2015;(3):125-35
Abstract
Obesity develops when energy intake exceeds energy expenditure over time. Numerous neurotransmitters, hormones, and factors have been implicated to coordinately control energy homeostasis, centrally and peripherally. However, the neuropeptide Y (NPY) system has emerged as the one with the most critical functions in this process. While NPY centrally promotes feeding and reduces energy expenditure, peptide YY (PYY) and pancreatic polypeptide (PP), the other family members, mediate satiety. Importantly, recent research has uncovered additional functions for these peptides that go beyond the simple feeding/satiety circuits and indicate a more extensive function in controlling energy homeostasis. In this review, we will discuss the actions of the NPY system in the regulation of energy balance, with a particular focus on energy expenditure.
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B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy.
Cavalieri, M, Schmidt, R, Chen, C, Mok, V, de Freitas, GR, Song, S, Yi, Q, Ropele, S, Grazer, A, Homayoon, N, et al
Stroke. 2012;(12):3266-70
Abstract
BACKGROUND AND PURPOSE Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions. METHODS A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities. RESULTS After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039). CONCLUSIONS Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. CLINICAL TRIAL REGISTRATION http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.
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VITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444).
, , Hankey, GJ, Algra, A, Chen, C, Wong, MC, Cheung, R, Wong, L, Divjak, I, Ferro, J, de Freitas, G, et al
International journal of stroke : official journal of the International Stroke Society. 2007;(2):144-50
Abstract
BACKGROUND Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke, dementia and depression. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B(12) and vitamin B(6), it is not known whether lowering tHcy, by means of B vitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. AIM: To determine whether the addition of B-vitamin supplements (folic acid 2 mg, B(6) 25 mg, B(12) 500 microg) to best medical and surgical management will reduce the combined incidence of stroke, myocardial infarction (MI) and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN A prospective, international, multicentre, randomised, double blind, placebo-controlled clinical trial. SETTING One hundred and four medical centres in 20 countries on five continents. SUBJECTS Eight thousand (6600 recruited as of 5 January, 2006) patients with recent (<7 months) stroke (ischaemic or haemorrhagic) or TIA (brain or eye). RANDOMISATION Randomisation and data collection are performed by means of a central telephone service or secure internet site. INTERVENTION One tablet daily of either placebo or B vitamins (folic acid 2 mg, B(6) 25 mg, B(12) 500 mug). PRIMARY OUTCOME The composite of stroke, MI or death from any vascular cause, whichever occurs first. Outcome and serious adverse events are adjudicated blinded to treatment allocation. SECONDARY OUTCOMES TIA, unstable angina, revascularisation procedures, dementia, depression. STATISTICAL POWER With 8000 patients followed up for a median of 2 years and an annual incidence of the primary outcome of 8% among patients assigned placebo, the study will have at least 80% power to detect a relative reduction of 15% in the incidence of the primary outcome among patients assigned B vitamins (to 6.8%/year), applying a two-tailed level of significance of 5%. CONCLUSION VITATOPS aims to recruit and follow-up 8000 patients between 1998 and 2008, and provide a reliable estimate of the safety and effectiveness of folic acid, vitamin B(12), and vitamin B(6) supplementation in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke throughout the world.
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Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial.
Dusitanond, P, Eikelboom, JW, Hankey, GJ, Thom, J, Gilmore, G, Loh, K, Yi, Q, Klijn, CJ, Langton, P, van Bockxmeer, FM, et al
Stroke. 2005;(1):144-6
Abstract
BACKGROUND AND PURPOSE Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability. METHODS We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability. RESULTS At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). CONCLUSIONS Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.
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Sustained homocysteine-lowering effect over time of folic acid-based multivitamin therapy in stroke patients despite increasing folate status in the population.
Hankey, GJ, Eikelboom, JW, Loh, K, Tang, M, Pizzi, J, Thom, J, Yi, Q
Cerebrovascular diseases (Basel, Switzerland). 2005;(2):110-6
Abstract
BACKGROUND AND AIMS It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy. METHODS We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined. RESULTS Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively; p < 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: -4.1, -4.1, -3.1 and -3.6 micromol/l in the first, second, third and fourth quartiles, respectively; p = 0.56). CONCLUSIONS The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.
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Is there really a power shortage in clinical trials testing the "homocysteine hypothesis?".
Hankey, GJ, Eikelboom, JW, Loh, K, Yi, Q, Pizzi, J, Tang, M, Hickling, S, Le, M, Klijn, CJ, Dusitanond, P, et al
Arteriosclerosis, thrombosis, and vascular biology. 2004;(8):e147