Anomalous subdiffusion in cells and model systems is an active area of research. The main questions are whether diffusion is anomalous or normal, and if it is anomalous, its mechanism. The subject is ...controversial, especially the hypothesis that crowding causes anomalous subdiffusion. Anomalous subdiffusion measurements would be strengthened by an experimental standard, particularly one able to cross-calibrate the different types of measurements. Criteria for a calibration standard are proposed. First, diffusion must be anomalous over the length and timescales of the different measurements. The length-scale is fundamental; the time scale can be adjusted through the viscosity of the medium. Second, the standard must be theoretically well understood, with a known anomalous subdiffusion exponent, ideally readily tunable. Third, the standard must be simple, reproducible, and independently characterizable (by, for example, electron microscopy for nanostructures). Candidate experimental standards are evaluated, including obstructed lipid bilayers; aqueous systems obstructed by nanopillars; a continuum percolation system in which a prescribed fraction of randomly chosen obstacles in a regular array is ablated; single-file diffusion in pores; transient anomalous subdiffusion due to binding of particles in arrays such as transcription factors in randomized DNA arrays; and computer-generated physical trajectories.
Anomalous subdiffusion has been reported for two-dimensional diffusion in the plasma membrane and three-dimensional diffusion in the nucleus and cytoplasm. If a particle diffuses in a suitable ...infinite hierarchy of binding sites, diffusion is well known to be anomalous at all times. But if the hierarchy is finite, diffusion is anomalous at short times and normal at long times. For a prescribed set of binding sites, Monte Carlo calculations yield the anomalous diffusion exponent and the average time over which diffusion is anomalous. If even a single binding site is present, there is a very short, almost artifactual, period of anomalous subdiffusion, but a hierarchy of binding sites extends the anomalous regime considerably. As is well known, an essential requirement for anomalous subdiffusion due to binding is that the diffusing particle cannot be in thermal equilibrium with the binding sites; an equilibrated particle diffuses normally at all times. Anomalous subdiffusion due to barriers, however, still occurs at thermal equilibrium, and anomalous subdiffusion due to a combination of binding sites and barriers is reduced but not eliminated on equilibration. This physical model is translated directly into a plausible biological model testable by single-particle tracking.
Weight gain is commonly observed during and after breast cancer treatment due to chemotherapy and endocrine therapies, induced menopause, changes in metabolism and food intake and decreased physical ...activity. Systematic reviews show that women who are overweight or obese at diagnosis, and those who gain weight, have poorer breast cancer survival outcomes than women of a healthy weight, irrespective of menopausal status. Excess body weight after breast cancer also increases the risk of type 2 diabetes mellitus and CVD. The adverse impact of excess body weight on survival outcomes is clearly shown for women with oestrogen receptor-positive (ER+) breast cancer, which accounts for 70 % of all breast cancer cases. Higher body fat is thought to increase the risk of ER+ recurrence because of increased aromatase activity. However, this could be compounded by other risk factors, including abnormal insulin and adipokine metabolism, impaired anti-tumour immunity and chronic low-grade systemic inflammation. Observational evidence linking poorer survival outcomes with excess body fat and low physical activity in women recovering from early-stage curative-intent breast cancer treatment is reviewed, before reflecting on the proposed biological mechanisms. The issues and sensitivities surrounding exercise participation amongst overweight breast cancer patients is also discussed, before providing an overview of the co-design process involved in development of an intervention (support programme) with appropriate content, structure and delivery model to address the weight management challenges faced by overweight ER+ breast cancer patients.
The objective of this study was to examine the association between the scores of the Children's Eating Behaviour Questionnaire (CEBQ) and BMI in a sample of Portuguese children. Using a ...cross-sectional design, a sample of 240 children (123 females and 117 males) aged 3-13 years were recruited from clinic and community-based settings. Parents completed the CEBQ to indicate their child's eating style for three 'food approach' and four 'food avoidant' sub-scales. Factor analyses revealed an underlying structure similar to the original CEBQ. Children's height and weight were measured to calculate BMI and Centre for Disease Control BMI z-scores. Hierarchical regression analyses controlling for gender, age and socioeconomic status indicated that all CEBQ sub-scales were significantly associated with BMI z-scores (P = 0·03 to < 0·001). Food approach scales were positively related to BMI z-scores (β = 0·33-0·51) and food avoidance negatively related (β = - 0·17 to - 0·46). Our results support the use of the CEBQ to further understand eating style as a behavioural pathway to obesity.
Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, particularly in women with oestrogen receptor-positive (ER +) disease. The ...aim of this study was to co-design (with patients) a programme of tailored, personalised support (intervention), including high-quality support materials, to help female breast cancer patients (BCPs) with ER + disease to develop the skills and confidence needed for sustainable weight loss. METHODS: ER + BCPs were recruited from two UK National Health Service (NHS) Trusts. The selection criteria included (i) recent experience of breast cancer treatment (within 36 months of completing primary treatment); (ii) participation in a recent focus group study investigating weight management perceptions and experiences; (iii) willingness to share experiences and contribute to discussions on the support structures needed for sustainable dietary and physical activity behaviour change. Co-design workshops included presentations and interactive activities and were facilitated by an experienced co-design researcher (HH), assisted by other members of the research team (KP, SW and JS).
Two groups of BCPs from the North of England (N = 4) and South Yorkshire (N = 5) participated in a two-stage co-design process. The stage 1 and stage 2 co-design workshops were held two weeks apart and took place between Jan-March 2019, with each workshop being approximately 2 h in duration. Guided by the Behaviour Change Wheel, a theoretically-informed weight management intervention was developed on the basis of co-designed strategies to overcome physical and emotional barriers to dietary and physical activity behaviour change. BCPs were instrumental in designing all key features of the intervention, in terms of Capability (e.g., evidence-based information, peer-support and shared experiences), Opportunity (e.g., flexible approach to weight management based on core principles) and Motivation (e.g., appropriate use of goal-setting and high-quality resources, including motivational factsheets) for behaviour change.
This co-design approach enabled the development of a theoretically-informed intervention with a content, structure and delivery model that has the potential to address the weight management challenges faced by BCPs diagnosed with ER + disease. Future research is required to evaluate the effectiveness of the intervention for eliciting clinically-important and sustainable weight loss in this population.
Background:
Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis (PwMS).
Objective:
The objective of this study was ...to assess the effects of a practically implemented exercise programme on self-directed exercise behaviour and important health outcomes in PwMS to nine months of follow-up.
Methods:
We conducted a parallel-arm, randomised controlled trial: 120 PwMS (Expanded Disability Status Scale (EDSS) 1.0–6.5) randomised to a three-month exercise intervention plus usual care, or usual care only. Two supervised plus one home-exercise session (weeks 1–6) were followed by one supervised and two home-exercise sessions (weeks 7–12). Cognitive-behavioural techniques promoted long-term exercise behaviour change. Outcomes were blindly assessed at baseline and at three and nine months after randomisation. The primary outcome was self-reported exercise behaviour (Godin Leisure Time Exercise Questionnaire (GLTEQ)). Secondary outcomes included fatigue and health-related quality of life (HRQoL).
Results:
The intervention increased self-reported exercise (9.6 points; 95% CI: 2.0 to 17.3 points; p = 0.01) and improved fatigue (p < 0.0001) and many HRQoL domains (p ≤ 0.03) at three months. The improvements in emotional well-being (p = 0.01), social function (p = 0.004) and overall quality of life (p = 0.001) were sustained for nine months.
Conclusion:
This pragmatic approach to implementing exercise increases self-reported exercise behaviour, improves fatigue and leads to a sustained enhancement of HRQoL domains in PwMS.
•One in five daily caffeine consumers exceed the recommended 400 mg daily limit.•85% of respondents report at least one caffeine-related harm in the past year.•20% of respondents met DSM-5 criteria ...for CUD, and 30% for caffeine withdrawal.•Medium and high (vs low) caffeine use tripled the odds of CUD.•Women and smokers may be more prone to CUD and withdrawal than men and non-smokers.
Caffeine Use Disorder (CUD) is not yet formally recognized in the DSM-5, but emerging evidence suggests CUD could impact up to one in five people. The primary aim of this study was to estimate levels of caffeine consumption and its associations with CUD and withdrawal, taking socio-demographic characteristics (age, gender, ethnicity, income) into account. Secondary aims were to measure caffeine-related harm and treatment preferences.
We administered an online cross-sectional survey via Facebook to a convenience sample of 2379 adults in New Zealand. Caffeine consumption was assessed across six products: coffee, tea, energy drinks, cola, alcohol mixed with caffeine, and other products (e.g., caffeine pills, sports supplements).
20% of participants met proposed criteria for CUD, with 30% meeting DSM-5 criteria for caffeine withdrawal. Moderate (200–400 mg per day) and high consumption (>400 mg per day) was associated with a three-fold increase in the odds of CUD and a two-fold increase in the odds of withdrawal. Women and current smokers were at higher risk of CUD and withdrawal even at moderate consumption levels. Nearly 85% of respondents experienced at least one caffeine-related harm in the past 12-months. The number of harms increased with level of caffeine consumption. Nearly 50% indicated a self-help treatment for caffeine reduction would be of interest.
High rates of CUD and caffeine withdrawal amongst moderate caffeine users, women and smokers suggests caffeine consumption guidelines may need refinement. Caffeine-related harm that is not clinically meaningful may still be of concern to individuals and warrants further investigation.
To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer.
Only randomised controlled trials (RCTs) that compared an ...exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012.
Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8-12 weeks (SMD=0.73, 95% CI=0.51-0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45-0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation.
Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis.
Lateral diffusion in the plasma membrane is obstructed by proteins bound to the cytoskeleton. The most important parameter describing obstructed diffusion is the percolation threshold. The thresholds ...are well known for point tracers, but for tracers of nonzero radius, the threshold depends on the excluded area, not just the obstacle concentration. Here thresholds are obtained for circular obstacles on the continuum. Random obstacle configurations are generated by Brownian dynamics or Monte Carlo methods, the obstacles are immobilized, and the percolation threshold is obtained by solving a bond percolation problem on the Voronoi diagram of the obstacles. The percolation threshold is expressed as the diameter of the largest tracer that can cross a set of immobile obstacles at a prescribed number density. For random overlapping obstacles, the results agree with the known analytical solution quantitatively. When the obstacles are soft disks with a 1/r12 repulsion, the percolating diameter is ∼20% lower than for overlapping obstacles. A percolation model predicts that the threshold is highly sensitive to the tracer radius. To our knowledge, such a strong dependence has so far not been reported for the plasma membrane, suggesting that percolation is not the factor controlling lateral diffusion. A definitive experiment is proposed.
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