👤 Anne Grote

Classification of physical activity (PA) depends on the cut-point method used to allocate PA counts from accelerometer measurements. This study investigates how three validated cut-point methods affect the time spent in various levels of PA and sedentary behaviour (SB), and how they impact toddlers estimated adherence to PA guidelines. PA was assessed using an ActiGraph wGT3X-BT accelerometer in a cohort of 653 two-year-old children participating in the Toddler Milk Intervention study. Children wearing the ActiGraph for at least four days, with a minimum of six hours wear-time per day, were included. Time spent in SB and different activity levels were estimated according to three cut-point methods and were standardized to individual mean wear-time. We used one cut-point method based on the vertical axis (VA) (Trost VA), with an epoch length of 15 s and two cut-point methods based on either the VA (Costa VA) or on the vector magnitude (VM) (Costa VM) with an epoch length of five seconds. Estimates of SB and PA for each method were compared with repeated measures ANOVA. The time toddlers spent in PA was significantly different depending on the cut-point methods. Costa VM classified on average 62 min (95% CI 61, 64] more per day as SB and 57 min (95% CI -58, -56] less per day as LPA compared to Trost VA (both p < 0.0001). For MVPA, the mean difference between Costa VA and Trost VA was 6.8 min (95% CI -7, -6; p < 0.0001). Concurrently, the proportion of children meeting the WHO recommendation of 180 min of total PA differed between cut-point methods, with 86% according to Costa VM and 97% according to Trost VA. The time toddlers engage in different intensities of PA is significantly determined by the selection of cut-point method. Notably, the use of a different cut-point method leads up to a 10% difference in the estimated time spent in LPA and SB, but only a 1% difference of moderate-vigorous PA. These differences change the estimated adherence to recommendations. Future research is needed to standardize the data processing methods for better comparability between studies analysing toddlers' PA. ClinicalTrials.gov, TRN: NCT02907502, Registration Date: 31 August 2016. Show less

In primary central nervous system tumours, epithelial-to-mesenchymal transition (EMT) gene expression is associated with increased malignancy. However, it has also been shown that EMT factors in gliomas are almost exclusively expressed by glioma vessel-associated pericytes (GA-Peris). In this study, we aimed to identify the mechanism of EMT in GA-Peris and its impact on angiogenic processes. In glioma patients, vascular density and the expression of the pericytic markers platelet derived growth factor receptor (PDGFR)-β and smooth muscle actin (αSMA) were examined in relation to the expression of the EMT transcription factor SLUG and were correlated with survival of patients with glioblastoma (GBM). Functional mechanisms of SLUG regulation and the effects on primary human brain vascular pericytes (HBVP) were studied in vitro by measuring proliferation, cell motility and growth characteristics. The number of PDGFR-β- and αSMA-positive pericytes did not change with increased malignancy nor showed an association with the survival of GBM patients. However, SLUG-expressing pericytes displayed considerable morphological changes in GBM-associated vessels, and TGF-β induced SLUG upregulation led to enhanced proliferation, motility and altered growth patterns in HBVP. Downregulation of SLUG or addition of a TGF-β antagonising antibody abolished these effects. We provide evidence that in GA-Peris, elevated SLUG expression is mediated by TGF-β, a cytokine secreted by most glioma cells, indicating that the latter actively modulate neovascularisation not only by modulating endothelial cells, but also by influencing pericytes. This process might be responsible for the formation of an unstructured tumour vasculature as well as for the breakdown of the blood-brain barrier in GBM. Show less