Establishing early physical activity (PA) habits is vital for long-term health, with parents considered as key influencers on children's PA. Yet, most previous parent-offspring dyads examining PA asso Show more
Establishing early physical activity (PA) habits is vital for long-term health, with parents considered as key influencers on children's PA. Yet, most previous parent-offspring dyads examining PA associations were cross-sectional, rarely used device-based measures, and often overlooked movement composition. The aim of this study was to determine whether mother's and father's waking movement composition is cross-sectionally or longitudinally associated with those of their children. The SOPHYA cohort recruited families from a nation-wide population-based random sample stratified by child's sex, birth year, and language. All youth aged 6-16 years and their parents officially residing in Switzerland, were eligible. Baseline and follow-up assessment occurred in 2013-2015 and 2019-2020, respectively. Questionnaire information and accelerometer measurements were collected remotely. The main predictor was parental movement composition at baseline. The associations between parental and child movement compositions were examined using Dirichlet regression models, adjusting for child's age and sex, parental education, and language region. The endpoints were children's movement composition at baseline (cross-sectional) and follow-up (longitudinal), respectively. Baseline assessment provided accelerometer and self-reported covariate data for the same measurement week in 686 mother-child and 373 father-child pairs. Follow-up assessment provided accelerometer data for 263 children with maternal and 149 with paternal baseline data. Cross-sectionally, replacing parental sedentary behaviour (SB) with moderate-to-vigorous activity (MVPA) (mothers: 0.10, p < 0.001; fathers: 0.09, p = 0.002) or replacing SB with light physical activity (LPA) (mothers: 0.13; < 0.001; fathers: 0.09; p < 0.005) was associated with similar, but smaller shifts in children. Longitudinally, replacing parental SB with LPA was associated with similar, but smaller shifts in children five years later (mothers: coefficient: 0.12, p = 0.021; fathers: coefficient: 0.10, p = 0.108). The cross-sectional change in children's LPA/SB ratio predicted from a parent's 20% decrease in SB and corresponding 20% increase in LPA was about 18-fold smaller than the observed maternal shift and about 29-fold smaller than the paternal shift from which it was predicted. Dirichlet regression results suggest that parental movement composition may predict children's movement composition, highlighting parental movement patterns, particularly SB, as potentially effective targets for short- and long-term interventions to increase PA in both parents and children. Show less
The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural Show more
The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents. Show less
Structural modification of a series of dual LXRα/β agonists led to the identification of a new class of LXRβ partial agonists. An X-ray co-crystal structure shows that a representative member of this Show more
Structural modification of a series of dual LXRα/β agonists led to the identification of a new class of LXRβ partial agonists. An X-ray co-crystal structure shows that a representative member of this series, pyrrole 5, binds to LXRβ with a reversed orientation compared to 1. Show less
The in vivo organ distribution of particulate drug carriers is decisively influenced by the interaction with plasma proteins after i.v. administration. Serum protein adsorption on lipid drug conjugate Show more
The in vivo organ distribution of particulate drug carriers is decisively influenced by the interaction with plasma proteins after i.v. administration. Serum protein adsorption on lipid drug conjugate nanoparticles, a new carrier system for i.v. application, was investigated by 2-dimensional electrophoresis (2-DE). The particles were surface-modified to target them to the brain. To assess the protein adsorption pattern after i.v. injection in mice prior to in vivo studies, the particles were incubated in mouse serum. Incubation in human serum was carried out in parallel to investigate similarities or differences in the protein patterns obtained from men and mice. Distinct differences were found. Particles incubated in human serum showed preferential adsorption of apolipoproteins A-I, A-IV and E. Previously, preferential adsorption of ApoE was reported as one important factor for targeting of Tween(R)80 modified polybutylcyanoacrylate nanoparticles to the brain. Preferential adsorption of ApoA-I and A-IV took place after incubation in mouse serum, adsorption of ApoE could not be clearly confirmed. In vivo localization of the LDC nanoparticles at the blood-brain barrier and diffusion of the marker Nile Red into the brain could be shown by confocal laser-scanning microscopy. Differences of the obtained adsorption patterns are discussed with regard to their relevance for correlations of in vitro and in vivo data obtained from different species. Show less