Understanding Self-Assembly and Molecular Packing in Methylcellulose Aqueous Solutions Using Multiscale Modeling and Simulations.

We present a multiscale molecular dynamics (MD) simulation study on self-assembly in methylcellulose (MC) aqueous solutions. First, using MD simulations with a new coarse-grained (CG) model of MC chains in implicit water, we establish how the MC chains self-assemble to form fibrils and fibrillar networks and elucidate the MC chains' packing within the assembled fibrils. The CG model for MC is extended from a previously developed model for unsubstituted cellulose and captures the directionality of H-bonding interactions between the -OH groups. The choice and placement of the CG beads within each monomer facilitates explicit modeling of the exact degree and position of methoxy substitutions in the monomers along the MC chain. CG MD simulations show that with increasing hydrophobic effect and/or increasing H-bonding strength, the commercial MC chains (with degree of methoxy substitution, DS, ∼1.8) assemble from a random dispersed configuration into fibrils. The assembled fibrils exhibit consistent fibril diameters regardless of the molecular weight and concentration of MC chains, in agreement with past experiments. Most MC chains' axes are aligned with the fibril axis, and some MC chains exhibit twisted conformations in the fibril. To understand the molecular driving force for the twist, we conduct atomistic simulations of MC chains preassembled in fibrils (without any chain twists) in explicit water at 300 and 348 K. These atomistic simulations also show that at DS = 1.8, MC chains adopt twisted conformations, with these twists being more prominent at higher temperatures, likely as a result of shielding of hydrophobic methyl groups from water. For MC chains with varying DS, at 348 K, atomistic simulations show a nonmonotonic effect of DS on water-monomer contacts. For 0.0 < DS < 0.6, the MC monomers have more water contacts than at DS = 0.0 or DS > 0.6, suggesting that with few methoxy substitutions, the MC chains are effectively hydrophilic, letting the water molecules diffuse into the fibril to participate in H-bonds with the MC chains' remaining -OH groups. At DS > 0.6, the MC monomers become increasingly hydrophobic, as seen by decreasing water contacts around each monomer. We conclude based on the atomistic observations that MC chains with lower degrees of substitutions (DS ≤ 0.6) should exhibit solubility in water over broader temperature ranges than DS ∼ 1.8 chains.

Physical Performance and Amyloid-ß in Humans: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Accumulation of amyloid-ß (Aß) plaques is one of the main features of Alzheimer's disease (AD). Physical performance has been related to dementia risk and Aß, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aß. Yet, no evidence synthesis has been performed in humans. OBJECTIVE: To investigate the association of physical performance with Aß in humans, including Aß accumulation on brain, and Aß abnormalities measured in cerebrospinal fluid (CSF) and blood. METHODS: A systematic review with multilevel meta-analysis was performed from inception to June 16th, 2022. Studies were eligible if they examined the association of physical performance with Aß levels, including the measure of physical performance as a predictor and the measure of Aß as an outcome in humans. RESULTS: 7 articles including 2,619 participants were included in the meta-analysis. The results showed that physical performance was not associated with accumulation of Aß in the brain (ES = 0.01; 95% CI -0.21 to 0.24; I2 = 69.9%), in the CSF (ES = -0.28; 95% CI -0.98 to 0.41; I2 = 91.0%) or in the blood (ES = -0.19; 95% CI -0.61 to 0.24; I2 = 99.75%). Significant heterogeneity was found across the results , which posed challenges in arriving at consistent conclusions; and the limited number of studies hindered the opportunity to conduct a moderation analysis. CONCLUSIONS: The association between physical performance and Aß is inconclusive. This uncertainly arises from the limited number of studies, study design limitations, and heterogeneity of measurement approaches. More studies are needed to determine whether physical performance is related to Aß levels in humans.

Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial.

INTRODUCTION: Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk. METHODS AND ANALYSIS: In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain-body interactions in the context of cardiovascular health. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. TRIAL REGISTRATION NUMBER: NCT03841669.

Changes in stress pathways as a possible mechanism of aerobic exercise training on brain health: a scoping review of existing studies.

Physical activity (PA) in the form of aerobic exercise (AE) preserves and improves neurocognitive function across the lifespan. However, a mechanistic understanding of the pathways by which aerobic exercise impacts brain health is still lacking, particularly with respect to stress-related pathways. One mechanistic hypothesis is that AE improves neurocognitive health in part by modifying circulating levels of stress-related hormones and signaling factors associated with the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS), as commonly measured by the biomarkers cortisol (CORT) and salivary α-amylase (sAA). Thus, this hypothesis predicts that changes in stress biomarkers, such as CORT and sAA, are possible explanatory pathways mediating the positive effects of AE on neurocognitive health. In the present review article, we provide a summary of available studies examining the possibility that exercise-induced changes to stress biomarkers could partly account for exercise-related improvements in neurocognitive health. Our review indicates that despite the intuitive appeal of this hypothesis, there is insufficient evidence available to conclude that chronic and habitual AE affects neurocognitive health by altering stress biomarker pathways. The cross-sectional nature of the majority of reviewed studies highlights the need for well-controlled studies to adequately test this hypothesis.

Differentiating the influence of sedentary behavior and physical activity on brain health in late adulthood.

Public health messaging calls for individuals to be more physically active and less sedentary, yet these lifestyle behaviors have been historically studied independently. Both physical activity (PA) and sedentary behavior (SB) are linked through time-use in a 24-hour day and are related to health outcomes, such as neurocognition. While the benefits of PA on brain health in late adulthood have been well-documented, the influence of SB remains to be understood. The purpose of this paper was to critically review the evolving work on SB and brain health in late adulthood and emphasize key areas of consideration to inform potential research. Overall, the existing literature studying the impact of SB on the components and mechanisms of brain health are mixed and inconclusive, provided largely by cross-sectional and observational work employing a variety of measurement techniques of SB and brain health outcomes. Further, many studies did not conceptually or statistically account for the role of PA in the proposed relationships. Therefore, our understanding of the way in which SB may influence neurocognition in late adulthood is limited. Future efforts should include more prospective longitudinal and randomized clinical trials with intentional methodological approaches to better understand the relationships between SB and the brain in late adulthood, and how these potential links are differentiated from PA.

Feasibility of Integration of Yoga in a Behavioral Weight-Loss Intervention: A Randomized Trial.

OBJECTIVE: This study examined the feasibility and comparison of two styles of yoga within the context of a standard behavioral weight-loss intervention (SBWI). METHODS: Fifty adults with obesity (BMI: 31.3 ± 3.8 kg/m2 ) participated in this 6-month study that included a SBWI and a calorie- and fat-reduced diet. Randomization was to restorative Hatha (SBWI+RES) or Vinyasa (SBWI+VIN) yoga. Yoga was prescribed to increase from 20 to 40 to 60 minutes per session across the intervention. Weight was assessed at baseline and 6 months. Perceptions of yoga were assessed at the completion of the intervention. RESULTS: Adjusted weight loss was -3.4 kg (95% CI: -6.4 to -0.5) in SBWI+RES and -3.8 kg (95% CI: -6.8 to -0.9) in SBWI+VIN (P < 0.001), with no difference between groups. Of all participants, 74.4% reported that they would continue participation in yoga after the SBWI. Session duration was a barrier as yoga increased from 20 to 40 to 60 minutes per day, with 0%, 7.5%, and 48.8% reporting this barrier, respectively. CONCLUSIONS: Among adults with obesity, yoga participation, within the context of a SBWI, appears to be feasible, with weight loss not differing by style of yoga. Progressing to 60 minutes per session appears to be a barrier to engagement in yoga in this population.

Strategies for Physical Activity Interventions in the Treatment of Obesity.

Physical activity contributes to body weight regulation. At least 150 minutes per week of moderate-to-vigorous intensity physical activity may be needed. When not coupled with dietary restriction, physical activity contributes to an average weight loss of approximately 2 to 3 kg in interventions up to 6 months in duration; when added to modest dietary restriction it adds 20% additional weight loss compared with modest dietary restriction alone. Physical activity is associated with enhanced long-term weight loss and attenuation of weight regain and should be included within clinical and public health approaches to prevent weight regain and to treat obesity.