In Vitro Response of Retinal Pigment Epithelial Cells Exposed to Chitosan Materials Prepared with Different Cross-Linkers

The interaction between cells and biopolymers is the evaluation indicator of the biocompatibility of materials. The purpose of this work was to examine the responses of retinal pigment epithelial (RPE) cells to genipin (GP) or glutaraldehyde (GTA) cross-linked chitosan by means of cell viability assays, cytokine expression analyses, and apoptosis assays. Evaluations of non-cross-linked chitosan were conducted simultaneously for comparison. Both GP and GTA treated samples with the same extent of cross-linking (around 80%) were prepared by varying cross-linking time. Our results showed that GP cross-linking was carried out by either radical polymerization of the monomers or SN2 nucleophilic substitution reaction involving the replacement of the ester group on the monomer with a secondary amide linkage. On the other hand, GTA could react with free amino groups of chitosan, leading to the formation of either the Schiff bases or the Michael-type adducts with terminal aldehydes. The biocompatibility of non-cross-linked chitosan membranes was demonstrated by the absence of any signs of toxicity or inflammation reaction. The present study showed that the ARPE-19 cells exposed to GTA cross-linked chitosan membranes had significantly higher cytotoxicity, interleukin-6 levels, and number of TUNEL-positive nuclei than did those exposed to GP treated samples. In addition, the materials modified with GTA trigger apoptosis at an early stage and may induce toxicity in the RPE cells later. The findings suggest that while the chitosan molecules bridged by GP are satisfactorily cytocompatible, the counterparts treated by GTA do not seem to be tolerated. In terms of material safety, the GP cross-linked chitosan may be compatible with human RPE cells and may have a potential application as delivery carriers in the treatment of posterior segment diseases

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Genomewide Scan for Gout in Taiwanese Aborigines Reveals Linkage to Chromosome 4q25

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all) statistic]; empirical P=.0006; LOD=4.3, P=4.4×10(-6) by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3×10(-6)). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene

Moderate Hypothermia (33 °C) Decreases the Susceptibility to Pacing-Induced Ventricular Fibrillation Compared with Severe Hypothermia (30 °C) by Attenuating Spatially Discordant Alternans in Isolated Rabbit Hearts

Background Severe hypothermia (SH, 30 °C) increases the risk of pacing-induced ventricular fibrillation (PIVF) by enhancing spatially discordant alternans (SDA). Whether moderate hypothermia (MH, 33 °C), which is clinically used for therapeutic hypothermia, also facilitates SDA remains unclear. We hypothesized that MH attenuates SDA occurrence compared with that achieved by SH, and decreases the susceptibility of PIVF. Methods Using an optical mapping system, action potential duration (APD)/conduction velocity restitutions and thresholds of APD alternans were determined by S1 pacing in Langendorff-perfused isolated rabbit hearts. In the MH group (n = 7), S1 pacing was performed at baseline (37 °C), after 5-min MH, and after 5-min rewarming (37 °C). In the SH group (n = 9), pacing was also performed at baseline (37 °C), after 5-min SH, and after 5-min rewarming (37 °C). The thresholds of APD alternans were defined as the longest S1 pacing cycle length at which APD alternans were detected. Results Although the thresholds of APD alternans were not different between the MH (273 ± 46 ms) and the SH (300 ± 35 ms) (p = 0.281) groups, SDA threshold was shorter (at a faster heart rate) during MH (228 ± 33 ms) than that during SH (289 ± 42 ms) (p = 0.028). At APD alternans threshold, SH hearts showed more SDA than that during MH (SH: 7 hearts, MH: 2 hearts, p = 0.049). SDA could be induced in all 9 SH hearts (100%), while only 4 MH hearts (57%) had SDA (p = 0.029). The PIVF inducibility during SH (44 ± 53%) was higher than that during MH (0%) (p = 0.043). Conclusions Compared with SH, the MH group showed greater attenuation of SDA and decreased the susceptibility of PIVF. Therefore, MH is safer as a procedural guideline for use in clinical therapeutic hypothermia than SH

The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan

Background: Epidemiology of fosfomycin susceptibility and the plasmid-mediated fosfomycinase genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Taiwan remain unclear. Methods: 642 CRKP clinical isolates were collected from a nation-wide surveillance study (16 hospitals) in Taiwan in 2012–2013. Antimicrobial susceptibilities were determined. PFGE and MLST determined the clonal relatedness. Carbapenemases and fosfomycinases genes were detected by PCR, and their flanking regions were determined by PCR and sequencing. Synergistic activity of meropenem with fosfomycin was examined by the checkerboard method. Results: In total, 36.4% (234/642) of CRKP isolates in Taiwan were resistant to fosfomycin. Among 234 fosfomycin-resistant CRKP isolates, PFGE analysis revealed 81 pulsotypes. Pulsotype XXIII (n = 63) was predominant and belonged to ST11. 71 had carbapnemases (65 blaKPC-2-positive, 1 blaVIM-1-positive and 5 blaIMP-8-positive) and 62 had fosfomycinases (35 fosA3-positive and 27 foskp96-positive). Only 18.5% (5/27) of foskp96-positive isolates carried foskp96 and blaKPC-2, while 71.4% (25/35) of fosA3-positive isolates contained fosA3 and blaKPC-2. There were five types of flanking sequences for fosA3, and 85.7% (30/35) of fosA3 genes were flanked by IS26, suggesting possible horizontal gene transfer. Synergistic effect of fosfomycin and meropenem was observed in all 25 randomly selected pulsotype XXIII strains (100%; 25/25), even those containing fosfomycinase (48%, 12/25) or carbapnemase (96%, 24/25). Conclusions: A clone (pulsotype XXIII, ST11) has been found to be prevailing among fosfomycin-resistant CRKP in Taiwan. According to the in vitro data, the combination of fosfomycin and meropenem is a potentially alternative choice

Fuzzy-identification-based adaptive backstepping control using a self-organizing fuzzy system

[[abstract]]In this paper, a fuzzy-identification-based adaptive backstepping control (FABC) scheme is proposed. The FABC system is composed of a backstepping controller and a robust controller. The backstepping controller, which uses a self-organizing fuzzy system (SFS) with the structure and parameter learning phases to on-line estimate the controlled system dynamics, is the principal controller, and the robust controller is designed to dispel the effect of approximation error introduced by the SFS. The developed SFS automatically generates and prunes the fuzzy rules by the proposed structure adaptation algorithm and the parameters of the fuzzy rules and membership functions tunes on-line in the Lyapunov sense. Thus, the overall closed-loop FABC system can guarantee that the tracking error and parameter estimation error are uniformly ultimately bounded; and the tracking error converges to a desired small neighborhood around zero. Finally, the proposed FABC system is applied to a chaotic dynamic system to show its effectiveness. The simulation results verify that the proposed FABC system can achieve favorable tracking performance even with unknown controlled system dynamics.[[incitationindex]]SCI[[booktype]]紙