Average acceleration and intensity gradient of primary school children and associations with indicators of health and wellbeing

Average acceleration (AvAcc) and intensity gradient (IG) have been proposed as standardised metrics describing physical activity (PA) volume and intensity, respectively. We examined hypothesised between-group PA differences in AvAcc and IG, and their associations with health and wellbeing indicators in children. ActiGraph GT9X wrist accelerometers were worn for 24-h·d−1 over seven days by 145 children aged 9-10. Raw accelerations were averaged per 5-s epoch to represent AvAcc over 24-h. IG represented the relationship between log values for intensity and time. Moderate-to-vigorous PA (MVPA) was estimated using youth cutpoints. BMI z-scores, waist-to-height ratio (WHtR), peak oxygen uptake (VO2peak), Metabolic Syndrome risk (MetS score), and wellbeing were assessed cross-sectionally, and 8-weeks later. Hypothesised between-group differences were consistently observed for IG only (p<.001). AvAcc was strongly correlated with MVPA (r=0.96), while moderate correlations were observed between IG and MVPA (r=0.50) and AvAcc (r=0.54). IG was significantly associated with health indicators, independent of AvAcc (p<.001). AvAcc was associated with wellbeing, independent of IG (p<.05). IG was significantly associated with WHtR (p<.01) and MetS score (p<.05) at 8-weeks follow-up. IG is sensitive as a gauge of PA intensity that is independent of total PA volume, and which relates to important health indicators in children

Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context

The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds

The backwards comparability of wrist worn GENEActiv and waist worn ActiGraph accelerometer estimates of sedentary time in children

Objectives: To examine the backward comparability of a range of wrist-worn accelerometer estimates of sedentary time (ST) with ActiGraph 100 count∙min-1 waist ST estimates. Design: Cross-sectional, secondary data analysis Method: One hundred and eight 10-11-year-old children (65 girls) wore an ActiGraph GT3X+ accelerometer (AG) on their waist and a GENEActiv accelerometer (GA) on their non-dominant wrist for seven days. GA ST data were classified using a range of thresholds from 23-56 mg. ST estimates were compared to AG ST 100 count∙min-1 data. Agreement between the AG and GA thresholds was examined using Cronbach’s alpha, intraclass correlation coefficients (ICC), limits of agreement (LOA), Kappa values, percent agreement, mean absolute percent error (MAPE) and equivalency analysis. Results: Mean AG total ST was 492.4 minutes over the measurement period. Kappa values ranged from 0.31-0.39. Percent agreement ranged from 68-69.9%. Cronbach’s alpha values ranged from 0.88-0.93. ICCs ranged from 0.59-0.86. LOA were wide for all comparisons. Only the 34 mg threshold produced estimates that were equivalent at the group level to the AG ST 100 count∙min-1 data though sensitivity and specificity values of ~64% and ~74% respectively were observed. Conclusions: Wrist-based estimates of ST generated using the 34 mg threshold are comparable with those derived from the AG waist mounted 100 count∙min-1 threshold at the group level. The 34 mg threshold could be applied to allow group-level comparisons of ST with evidence generated using the ActiGraph 100 count∙min-1 method though it is important to consider the observed sensitivity and specificity results when interpreting findings

Can patients with low health literacy be identified from routine primary care health records? A cross-sectional and prospective analysis.

BACKGROUND: People with low health literacy (HL) are at increased risk of poor health outcomes, and receive less benefit from healthcare services. However, healthcare practitioners can effectively adapt healthcare information if they are aware of their patients' HL. Measurements are available to assess HL levels but may not be practical for use within primary care settings. New alternative methods based on demographic indicators have been successfully developed, and we aim to test if such methodology can be applied to routinely collected consultation records. METHODS: Secondary analysis was carried out from a recently completed prospective cohort study that investigated a primary care population who had consulted about a musculoskeletal pain problem. Participants completed questionnaires (assessing general health, HL, pain, and demographic information) at baseline and 6 months, with linked data from the participants' consultation records. The Single Item Literacy Screener was used as a benchmark for HL. We tested the performance of an existing demographic assessment of HL, whether this could be refined/improved further (using questionnaire data), and then test the application in primary care consultation data. Tests included accuracy, sensitivity, specificity, and area under the curve (AUC). Finally, the completed model was tested prospectively using logistic regression producing odds ratios (OR) in the prediction of poor health outcomes (physical health and pain intensity). RESULTS: In total 1501 participants were included within the analysis and 16.1% were categorised as having low HL. Tests for the existing demographic assessment showed poor performance (AUC 0.52), refinement using additional components derived from the questionnaire improved the model (AUC 0.69), and the final model using data only from consultation data remained improved (AUC 0.64). Tests of this final consultation model in the prediction of outcomes showed those with low HL were 5 times more likely to report poor health (OR 5.1) and almost 4 times more likely to report higher pain intensity (OR 3.9). CONCLUSIONS: This study has shown the feasibility of the assessment of HL using primary care consultation data, and that people indicated as having low HL have poorer health outcomes. Further refinement is now required to increase the accuracy of this method

Comparability of children’s sedentary time estimates derived from wrist worn GENEActiv and hip worn ActiGraph accelerometer thresholds

Objectives: to examine the comparability of children’s free-living sedentary time (ST) derived from raw acceleration thresholds for wrist mounted GENEActiv accelerometer data, with ST estimated using the waist mounted ActiGraph 100 count∙min-1 threshold. Design: Secondary data analysis Method: 108 10-11-year-old children (n=43 boys) from Liverpool, UK wore one ActiGraph GT3X+ and one GENEActiv accelerometer on their right hip and left wrist, respectively for seven days. Signal vector magnitude (SVM; mg) was calculated using the ENMO approach for GENEActiv data. ST was estimated from hip-worn ActiGraph data, applying the widely used 100 count∙min-1 threshold. ROC analysis using 10-fold hold-out cross-validation was conducted to establish a wrist-worn GENEActiv threshold comparable to the hip ActiGraph 100 count∙min-1 threshold. GENEActiv data were also classified using three empirical wrist thresholds and equivalence testing was completed. Results: Analysis indicated that a GENEActiv SVM value of 51mg demonstrated fair to moderate agreement (Kappa: 0.32-0.41) with the 100 count∙min-1 threshold. However, the generated and empirical thresholds for GENEActiv devices were not significantly equivalent to ActiGraph 100 count∙min-1. GENEActiv data classified using the 35.6 mg threshold intended for ActiGraph devices generated significantly equivalent ST estimates as the ActiGraph 100 count∙min-1. Conclusions: The newly generated and empirical GENEActiv wrist thresholds do not provide equivalent estimates of ST to the ActiGraph 100 count∙min-1 approach. More investigation is required to assess the validity of applying ActiGraph cutpoints to GENEActiv data. Future studies are needed to examine the backward compatibility of ST data and to produce a robust method of classifying SVM-derived ST

Converting between estimates of moderate-to-vigorous physical activity derived from raw accelerations measured at the wrist and from ActiGraph counts measured at the hip: The Rosetta Stone

The ability to compare published group-level estimates of objectively measured moderate-to-vigorous physical activity (MVPA) across studies continues to increase in difficulty. The objective of this study was to develop conversion equations and demonstrate their utility to compare estimates of MVPA derived from the wrist and hip. Data from three studies of youth (N = 232, 9-12yrs, 50% boys) who concurrently wore a hip-worn ActiGraph and a wrist-worn GENEActiv for 7-days. ActiGraph hip count data were reduced using four established cutpoints: Evenson, Pate, Puyau, and Freedson 3MET. Wrist accelerations were reduced using the Hildebrand MVPA 200 mg threshold. Conversion equations were developed on a randomly selected subsample of 132 youth. Equations were cross-validated and absolute error, absolute percent error, and modified Bland-Altman plots were evaluated for conversion accuracy. Across equations R2adj was 0.51-0.56 with individual-level absolute error in minutes ranging from 7 (wrist-to-hip Puyau) to 14.5 minutes (wrist-to-hip Freedson 3MET) and absolute percent differences ranging from 13.9%-24.5%. Group-level cross-validation to convert hip-to-wrist MVPA resulted in average absolute percent errors ranging from 3.1%-4.9%. Conversion of wrist- to-hip MVPA resulted in average absolute percent errors ranging from 3.0%-10.0%. We recommend the use of these equations to compare published estimates of MVPA between the wear-site cut-point combinations presented

Seasonal variation in objectively measured physical activity, sedentary time, cardio-respiratory fitness and sleep duration among 8–11 year-old Danish children: a repeated-measures study

Abstract Background Understanding fluctuations in lifestyle indicators is important to identify relevant time periods to intervene in order to promote a healthy lifestyle; however, objective assessment of multiple lifestyle indicators has never been done using a repeated-measures design. The primary aim was, therefore, to examine between-season and within-week variation in physical activity, sedentary behaviour, cardio-respiratory fitness and sleep duration among 8–11 year-old children. Methods A total of 1021 children from nine Danish schools were invited to participate and 834 accepted. Due to missing data, 730 children were included in the current analytical sample. An accelerometer was worn for 7 days and 8 nights during autumn, winter and spring, from which physical activity, sedentary time and sleep duration were measured. Cardio-respiratory fitness was assessed using a 10-min intermittent running test. Results The children had 5% more sedentary time, 23% less time in moderate-to-vigorous physical activity and 2% longer sleep duration during winter compared to spring and cardio-respiratory fitness was 4% higher during spring compared to autumn (P < 0.001). Sedentary time was higher and total physical activity, moderate-to-vigorous physical activity and sleep duration (boys only) were lower during weekends at all seasons (P ≤ 0.01). Intraclass correlation coefficients between seasons ranged from 0.47-0.74, leaving 45-78% to seasonal variation. Conclusions Overall, sedentary time was higher and physical activity lower during winter and during weekends. The most accurate and unbiased estimates of physical activity came from autumn; however, the considerable intra-individual variation suggests that a single measurement may not adequately characterise children’s habitual sleep and activity

A Multiwell Platform for Studying Stiffness-Dependent Cell Biology

Adherent cells are typically cultured on rigid substrates that are orders of magnitude stiffer than their tissue of origin. Here, we describe a method to rapidly fabricate 96 and 384 well platforms for routine screening of cells in tissue-relevant stiffness contexts. Briefly, polyacrylamide (PA) hydrogels are cast in glass-bottom plates, functionalized with collagen, and sterilized for cell culture. The Young's modulus of each substrate can be specified from 0.3 to 55 kPa, with collagen surface density held constant over the stiffness range. Using automated fluorescence microscopy, we captured the morphological variations of 7 cell types cultured across a physiological range of stiffness within a 384 well plate. We performed assays of cell number, proliferation, and apoptosis in 96 wells and resolved distinct profiles of cell growth as a function of stiffness among primary and immortalized cell lines. We found that the stiffness-dependent growth of normal human lung fibroblasts is largely invariant with collagen density, and that differences in their accumulation are amplified by increasing serum concentration. Further, we performed a screen of 18 bioactive small molecules and identified compounds with enhanced or reduced effects on soft versus rigid substrates, including blebbistatin, which abolished the suppression of lung fibroblast growth at 1 kPa. The ability to deploy PA gels in multiwell plates for high throughput analysis of cells in tissue-relevant environments opens new opportunities for the discovery of cellular responses that operate in specific stiffness regimes

Development of a complex intervention to test the effectiveness of peer support in type 2 diabetes

BACKGROUND: Diabetes is a chronic illness which requires the individual to assume responsibility for their own care with the aim of maintaining glucose and blood pressure levels as close to normal as possible. Traditionally self management training for diabetes has been delivered in a didactic setting. In recent times alternatives to the traditional delivery of diabetes care have been investigated, for example, the concept of peer support which emphasises patient rather than professional domination. The aim of this paper is to describe the development of a complex intervention of peer support in type 2 diabetes for a randomised control trial in a primary care setting. METHODS: The Medical Research Council (MRC) framework for the development and evaluation of complex interventions for randomised control trials (RCT) was used as a theoretical guide to designing the intervention. The first three phases (Preclinical Phase, Phase 1, Phase 2) of this framework were examined in depth. The Preclinical Phase included a review of the literature relating to type 2 diabetes and peer support. In Phase 1 the theoretical background and qualitative data from 4 focus groups were combined to define the main components of the intervention. The preliminary intervention was conducted in Phase 2. This was a pilot study conducted in two general practices and amongst 24 patients and 4 peer supporters. Focus groups and semi structured interviews were conducted to collect additional qualitative data to inform the development of the intervention. RESULTS: The four components of the intervention were identified from the Preclinical Phase and Phase 1. They are: 1. Peer supporters; 2. Peer supporter training; 3. Retention and support for peer supporters; 4. Peer support meetings. The preliminary intervention was implemented in the Phase 2. Findings from this phase allowed further modeling of the intervention, to produce the definitive intervention. CONCLUSION: The MRC framework was instrumental in the development of a robust intervention of peer support of type 2 diabetes in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42541690