Martinussensonne1481

Background There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. Methods This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer's Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural differentiation provides a powerful alternative tool to understand the cellular aspects of human neurological disorders. In this review, we summarize recent progress on studying mRNA targeting and local protein synthesis in stem cell-derived neurons, and discuss how perturbation of these processes may impact synapse development and functions that are relevant to cognitive deficits in ASD.Background Exosomes derived from mesenchymal stem cells (MSC-exos) have been demonstrated with great potential in the treatment of multiple human diseases including acute kidney injury (AKI) by virtue of their intrinsic cargoes. However, there are major challenges of low yield and the lack of an established biomanufacturing platform to efficiently produce MSC-exos, thereby limiting their therapeutic application. Here, we aimed to establish a novel strategy to produce MSC-exos with a hollow fiber bioreactor-based three-dimensional (3D) culture system and evaluate the therapeutic efficacy of 3D-exosomes (3D-exos) on AKI. Methods Mesenchymal stem cells (MSCs) were isolated from fresh human umbilical cord and cultured in two-dimensional (2D) flasks. 2 × 108 MSCs were inoculated into the hollow fiber bioreactor for 3D culture. The culture supernatants were collected every 1 or 2 days for isolating exosomes. Exosomes from 2D (2D-exos) and 3D cultures were characterized by transmission electron microscopy, nanopartiration. Impressively, 3D-exos were more effective than 2D-exos. Moreover, 3D-exos were taken up by tubular epithelial cells (TECs) with improved efficiency, thereby exhibiting superior anti-inflammatory effect and improved viability of TECs in vitro. Conclusions In summary, our findings demonstrate that the hollow fiber 3D culture system provides an efficient strategy for the continuous production of MSC-exos which has enhanced therapeutic potential for cisplatin-induced AKI.Background and purpose Interpretation of T2 values remains difficult due to limited comparability across hardware and software systems and the lack of validated measurement recommendations for the number and orientation of mandatory slices. Rapamune research buy Our aims were to provide a standardized comparison of intra- and inter-individual T2 values in the short and long axes and to investigate inter-scanner reproducibility. Method and materials Ninety cardiovascular magnetic resonance (CMR) studies in 30 healthy subjects were performed with three identical 1.5 T CMR scanners (same hardware and software) using a balanced steady-state free precession (bSSFP) gradient echo sequence in three short axis (SAx) and three long axis (LAx) views. A commercially available T2 mapping software package of the latest generation with automatic in-line motion correction was used for acquisition. Regions of interest were manually drawn in each of the 16 myocardial segments according to the American Heart Association (AHA) model in three SAx and three LAx acquisitions. Analysis of inter-scanner, inter-segmental, intra-segmental, inter-regional and inter-level differences was performed. Results Inter-scanner reproducibility was high and the mean myocardial T2 value for all evaluated segments was 45.7 ± 3.4 ms. Significant inter-segmental variations of mean T2 values were found. Mean intra-segmental T2 values were comparable between LAx and SAx acquisitions in 72%. Significantly higher T2 values were found in apical segments and a significant disparity among different regions was found for SAx and LAx orientations. Conclusion Standardized cardiac T2 mapping is highly reproducible on identical CMR systems. T2 values vary significantly between single heart segments, regions, levels, and axes in young, healthy subjects.Background Although Staphylococcus aureus bloodstream infections (SA-BSI) are a common and important infection, polymicrobial SA-BSI are infrequently reported. The aim of this study was to investigate the clinical characteristics and risk factors of polymicrobial SA-BSI in comparison with monomicrobial SA-BSI. Methods A single-center retrospective observational study was performed between Jan 1, 2013, and Dec 31, 2018 at a tertiary hospital. All patients with SA-BSI were enrolled, and their clinical data were gathered by reviewing electronic medical records. Results A total of 349 patients with SA-BSI were enrolled including 54 cases (15.5%) with polymicrobial SA-BSI. In multivariable analysis, burn injury (adjusted odds ratio [OR], 7.04; 95% confidence interval [CI], 1.71-28.94), need of blood transfusion (aOR, 2.72; 95% CI, 1.14-6.50), use of mechanical ventilation (aOR, 3.11; 95% CI, 1.16-8.30), the length of prior hospital stay (aOR, 1.02; 95% CI, 1.00-1.03), and pneumonia as primary site of infection (aOR, 4.