Sertraline associated with gold nanoparticles reduce cellular toxicity and induce sex-specific responses in behavior and neuroinflammation biomarkers in a mouse model of anxiety.

This study aimed to evaluate the effects of sertraline associated with gold nanoparticles (AuNPs) in vitro cell viability and in vivo behavior and inflammatory biomarkers in a mouse model of anxiety. Sertraline associated with AuNPs were synthesized and characterized. For the in vitro study, NIH3T3 and HT-22 cells were treated with different doses of sertraline, AuNPs, and sertraline + AuNPs and their viability was evaluated using the MTT assay. For the in vivo study, pregnant Swiss mice were administered a single dose of lipopolysaccharide (LPS) on the ninth day of gestation. The female and male offspring were divided into five treatment groups on PND 60 and administered chronic treatment for 28 days. The animals were subjected to behavioral testing and were subsequently euthanized. Their brains were collected and analyzed for inflammatory biomarkers. Sertraline associated with AuNPs exhibited significant changes in surface characteristics and increased diameters. Different doses of sertraline + AuNPs showed higher cell viability in NIH3T3 and HT-22 cells compared with sertraline alone. The offspring of LPS-treated dams exhibited anxiety-like behavior and neuroinflammatory biomarker changes during adulthood, which were ameliorated via sertraline + AuNPs treatment. The treatment response was sex-dependent and brain region-specific. These results suggest that AuNPs, which demonstrate potential to bind to other molecules, low toxicity, and reduced inflammation, can be synergistically used with sertraline to improve drug efficacy and safety by decreasing neuroinflammation and sertraline toxicity.

Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.