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- Watt, F. E., et al.
(författare)
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Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
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- Kam, K., et al.
(författare)
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Sleep oscillation-specific associations with Alzheimer's disease CSF biomarkers: novel roles for sleep spindles and tau
- 2019
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBased on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF A(42), P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.MethodsOne-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF A(42), P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.ResultsSpindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF A(42), P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.ConclusionsReduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
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- Lau, Hang Kuen, et al.
(författare)
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Microstructured Elastomer-PEG Hydrogels via Kinetic Capture of Aqueous Liquid–Liquid Phase Separation
- 2018
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Ingår i: Advanced Science. - : Wiley. - 2198-3844 .- 2198-3844. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Heterogeneous hydrogels with desired matrix complexity are studied for a variety of biomimetic materials. Despite the range of such microstructured materials described, few methods permit independent control over microstructure and microscale mechanics by precisely controlled, single-step processing methods. Here, a phototriggered crosslinking methodology that traps microstructures in liquid–liquid phase-separated solutions of a highly elastomeric resilin-like polypeptide (RLP) and poly(ethylene glycol) (PEG) is reported. RLP-rich domains of various diameters can be trapped in a PEG continuous phase, with the kinetics of domain maturation dependent on the degree of acrylation. The chemical composition of both hydrogel phases over time is assessed via in situ hyperspectral coherent Raman microscopy, with equilibrium concentrations consistent with the compositions derived from NMR-measured coexistence curves. Atomic force microscopy reveals that the local mechanical properties of the two phases evolve over time, even as the bulk modulus of the material remains constant, showing that the strategy permits control of mechanical properties on micrometer length scales, of relevance in generating mechanically robust materials for a range of applications. As one example, the successful encapsulation, localization, and survival of primary cells are demonstrated and suggest the potential application of phase-separated RLP-PEG hydrogels in regenerative medicine applications.
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- Parekh, Niyati, et al.
(författare)
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Associations of Parental Self-Efficacy With Diet, Physical Activity, Body Composition, and Cardiorespiratory Fitness in Swedish Preschoolers: Results From the MINISTOP Trial
- 2018
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Ingår i: Health Education & Behavior. - : SAGE PUBLICATIONS INC. - 1090-1981 .- 1552-6127. ; 45:2, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- Background. High parental self-efficacy (PSE) has been associated with healthy diets and higher levels of physical activity (PA) in children; however, data on PSE in relation to body weight and body composition are scarce. The objective of this study was to investigate associations of PSE with measures of diet, PA, body composition, and physical fitness in early childhood. Method. We used baseline data from the MINISTOP trial in healthy Swedish children (n = 301; 4.5 +/- 0.15 years). PSE was assessed using a questionnaire, dietary data were collected using a mobile technology-assisted methodology, and PA was obtained (sedentary behavior and moderate-to-vigorous) by accelerometry. Body composition was measured using the pediatric option for BodPod and cardiorespiratory fitness by the 20 m shuttle run. Linear regression was conducted to evaluate cross-sectional associations of the outcomes in relation to total PSE and scores computed for the individual PSE factors: (1) diet, (2) limit setting of unhealthful behaviors, and (3) PA. Results. Higher scores of total PSE and the diet factor were associated with higher fruit intake ( = 0.82 g/point and 1.99 g/point; p = .014 and .009, respectively) and lower consumption of unhealthy snacks ( = -0.42 g/point and -0.89 g/point; p = .012 and .020, respectively) after adjustment for parental body mass index and education, respondent, and childs sex and age. No associations were observed between PSE and PA, body composition, or cardiorespiratory fitness. Conclusions. Our study noted that PSE should be considered in conjunction with other strategies for a sustainable impact on childhood obesity.
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- Varga, A. W., et al.
(författare)
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Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid A beta 42 Levels in Cognitively Normal Elderly
- 2016
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 39:11, s. 2041-2048
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (A beta). We thus aimed to examine relationships between concentrations of A beta 42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF A beta 42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" A beta 42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF A beta 42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF A beta 42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF A beta 42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF A beta 42, suggesting that disturbed sleep might drive an increase in soluble brain A beta levels prior to amyloid deposition.
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