The aims of the study were to identify subclinical global systolic function abnormalities and evaluate influencing factors associated with left ventricular (LV) strain parameters in hypertensive subjects using cardiovascular magnetic resonance imaging feature tracking (CMR-FT). The study enrolled 57 patients with essential hypertension (mean age 43.04 ± 10.90 years; 35 males) and 26 healthy volunteers (mean age 38.69 ± 10.44 years; 11 males) who underwent clinical evaluation and CMR examination. Compared with controls, hypertensive patients had significantly impaired myocardial strain values while ejection fraction (EF) did not differ. After multivariate regression analyses adjustment for confounders, the global radial strains (GRS) was independently associated with the mean arterial pressure (MAP) and left ventricular mass index (LVMI) (β = -0.219, p = 0.009 and β = -0.224, p = 0.015, respectively; Adjusted R2 = 0.4); the global circumferential strains (GCS) was also independently associated with the MAP and LVMI (β = 0.084, p = 0.002 and β = 0.073, p = 0.01, respectively; Adjusted R2 = 0.439); the global longitudinal strains (GLS) was independently associated with the Age and MAP (β = 0.065, p = 0.021 and β = 0.077, p = 0.009, respectively; Adjusted R2 = 0.289). Myocardial strain can early detect the myocardial damage and may be an appropriate target for preventive strategies before abnormalities of EF.Modern cytometry methods allow collecting complex, multi-dimensional data sets from heterogeneous cell populations at single-cell resolution. While methods exist to describe the progression and order of cellular processes from snapshots of such populations, these descriptions are limited to arbitrary pseudotime scales. Here we describe MAPiT, an universal transformation method that recovers real-time dynamics of cellular processes from pseudotime scales by utilising knowledge of the distributions on the real scales. As use cases, we applied MAPiT to two prominent problems in the flow-cytometric analysis of heterogeneous cell populations (1) recovering the kinetics of cell cycle progression in unsynchronised and thus unperturbed cell populations, and (2) recovering the spatial arrangement of cells within multi-cellular spheroids prior to spheroid dissociation for cytometric analysis. Since MAPiT provides a theoretic basis for the relation of pseudotime values to real temporal and spatial scales, it can be used broadly in the analysis of cellular processes with snapshot data from heterogeneous cell populations.Hartmann's reversal procedures are often fraught with complications or failure to recover. This being a fact, it is often difficult to select patients with the optimal indications for a reversal. The post-recovery morbidity and mortality rates in the literature are heterogeneous between 0.8 and 44%. The identification of predictive risk factors of failure of such interventions would therefore be very useful to help the practitioner in his approach. Given these elements, it was important to us to analyze the practice of two French university hospitals in order to highlight such risk factors and to allow surgeons to select the best therapeutic strategy. We performed a bicentric observational retrospective study between 2010 and 2015 that studied the characteristics of patients who had undergone Hartmann surgery and were subsequently reestablished. The aim of the study was to identify factors influencing morbidity and postoperative mortality of Hartmann's reversal. Primary outcome was complications within the fia after Hartmann's reversal. Precarious nutritional status and cardiovascular comorbidities should clearly lead us to reconsider the surgical indication for continuity restoration.Phenylketonuria is a genetic disorder affecting the metabolism of phenylalanine (phe) due to a deficiency in the enzyme phenylalanine hydroxylase. This disorder is characterized by an elevated phe blood level, which can lead to severe intellectual disabilities in newborns. The current strategy to prevent these devastating consequences is limited to a life-long phe-free diet, which implies major lifestyle changes and restrictions. Recently, an injectable enzyme replacement therapy, Pegvaliase, has been approved for treating phenylketonuria, but is associated with significant side-effects. In this study a phe-metabolizing system suitable for oral delivery is designed to overcome the need for daily injections. Active phenylalanine ammonia-lyase (PAL), an enzyme that catalyses phe metabolism, is loaded into mesoporous silica microparticles (MSP) with pore sizes ranging from 10 to 35 nm. The surface of the MSP is lined with a semipermeable barrier to allow permeation of phe while blocking digestive enzymes that degrade PAL. The enzymatic activity can be partially preserved in vitro by coating the MSP with poly(allylamine) and poly(acrylic acid)-bowman birk (protease inhibitor) conjugate. The carrier system presented herein may provide a general approach to overcome gastro-intestinal proteolytic digestion and to deliver active enzymes to the intestinal lumen for prolonged local action.Recently, the critical roles played by genetic variants of TREM2 (Triggering Receptor Expressed on Myeloid cells 2) in Alzheimer's disease have been aggressively highlighted. https://www.selleckchem.com/products/abt-199.html However, few studies have focused on the deleterious roles of Nasu-Hakola disease (NHD) associated TREM2 variants. In order to get insights into the contributions made by these variants to neurodegeneration, we investigated the influences of four NHD associated TREM2 mutations (Y38C, W50C, T66M, and V126G) on loss-of-function, and followed this with in silico prediction and conventional molecular dynamics simulation. NHD mutations were predicted to be highly deleterious by eight different in silico bioinformatics tools and found to induce conformational changes by molecular dynamics simulation. As compared with the wild-type, the four variants produced substantial differences in the collective motions of loop regions, which not only promoted structural remodeling in the CDR2 (complementarity-determining region 2) loop but also in the CDR1 loop, by changing inter- and intra-loop hydrogen bonding networks. |