Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Acinetobacter baumannii </it>is a nosocomial pathogen of increasing importance, but the pathogenic mechanism of this microorganism has not been fully explored. This study investigated the potential of <it>A. baumannii </it>to invade epithelial cells and determined the role of <it>A. baumannii </it>outer membrane protein A (AbOmpA) in interactions with epithelial cells.</p> <p>Results</p> <p><it>A. baumannii </it>invaded epithelial cells by a zipper-like mechanism, which is associated with microfilament- and microtubule-dependent uptake mechanisms. Internalized bacteria were located in the membrane-bound vacuoles. Pretreatment of recombinant AbOmpA significantly inhibited the adherence to and invasion of <it>A. baumannii </it>in epithelial cells. Cell invasion of isogenic AbOmpA^-mutant significantly decreased as compared with wild-type bacteria. In a murine pneumonia model, wild-type bacteria exhibited a severe lung pathology and induced a high bacterial burden in blood, whereas AbOmpA^-mutant was rarely detected in blood.</p> <p>Conclusion</p> <p><it>A. baumannii </it>adheres to and invades epithelial cells. AbOmpA plays a major role in the interactions with epithelial cells. These findings contribute to the understanding of <it>A. baumannii </it>pathogenesis in the early stage of bacterial infection.</p

Emergent localized states at the interface of a twofold PT\mathcal{PT}-symmetric lattice

We consider the role of non-triviality resulting from a non-Hermitian Hamiltonian that conserves twofold PT-symmetry assembled by interconnections between a PT-symmetric lattice and its time reversal partner. Twofold PT-symmetry in the lattice produces additional surface exceptional points that play the role of new critical points, along with the bulk exceptional point. We show that there are two distinct regimes possessing symmetry-protected localized states, of which localization lengths are robust against external gain and loss. The states are demonstrated by numerical calculation of a quasi-1D ladder lattice and a 2D bilayered square lattice.Comment: 10 pages, 7 figure

Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

<p>Abstract</p> <p>Background</p> <p>Enzyme replacement therapy (ERT) with α-galactosidase A (α-Gal A) is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT.</p> <p>Methods</p> <p>A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA) was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3) levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted.</p> <p>Results</p> <p>Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT.</p> <p>Conclusions</p> <p>The rAAV2/8-hAGA mediated α-Gal A gene therapy provided improved efficiency over ERT in the Fabry disease mouse model. Furthermore, rAAV2/8-hAGA-mediated expression showed a greater effect in the kidney than ERT.</p

Results of Endoscopic Dacryocystorhinostomy under Local Anesthesia with Minimal Sedation

Purpose. We evaluated the tolerability and efficacy of endoscopic dacryocystorhinostomy (Endo-DCR) in patients treated in the leaning position and under local anesthesia with minimal sedation (LAS). Study Design. Questionnaire to determine subjective success of Endo-DCR. Methods. From May 2013 to August 2014, a total of 95 eyes with epiphora presented to the Myoung Eye Plastic Surgery Clinic in Seoul, Korea, and were treated with Endo-DCR under LAS. Three nerve blocks were administered to achieve local anesthesia. Postoperatively, the wound site was packed with Nasopore to control bleeding and promote wound healing. Outcome measures included a patient questionnaire completed on postoperative day 7 to evaluate intraoperative and postoperative pain based on the VAS (0 to 10). Results. Mean intraoperative and postoperative pain scores were 1.03 and 1.64, respectively, for 95 eyes. Of the 95 eyes treated, the patients in 82 eyes (86.31%) reported that they would prefer LAS over GA for a repeat Endo-DCR. The subjective and objective surgical success rates were 90.14% and 95.77%, respectively. Conclusions. Endo-DCR carried out under LAS with the patient in the leaning position is more useful, efficient, and feasible than Endo-DCR performed under GA with the patient in the supine position

Improved performance of polymer light-emitting diodes with nanocomposites

The characteristics of a hybrid polymer light-emitting diode (HPLED) with an active layer of poly [2-methoxy,5-(2-ethylhexoxy)-1,4-phenylenevinylene] blended with Au-capped TiO(2) nanocomposites are reported. Both the increased current in the active layer and low turn-on voltage were attributed to incorporation of Au-capped TiO(2) in the electroluminescent polymer. The maximal brightness of 11 630 cd/m(2) was observed in HPLED with a 1:1 ratio of Au-capped TiO(2). The enhanced performance was attributed to the roughness assisted charge transport induced by the Au-capped TiO(2) nanocomposites in the active polymer.open111

A Single-Center, Randomized Double-Blind Placebo-Controlled Study Evaluating the Effects of Poly-Gamma-Glutamate on Human NK Cell Activity after an 8-Week Oral Administration in Healthy Volunteers

A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly-γ-glutamate (γ-PGA) on human natural killer (NK) cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high dosage) of γ-PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ-PGA group were significantly higher (P<0.05 for all comparisons) compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production). These results suggest that the oral administration of γ-PGA induces a cell-mediated immunity by increasing the NK cell activity in humans

A nanohybrid system for taste masking of sildenafil

A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN–MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN–MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN–MMT and Viagra®, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN–MMT during the first 2 hours while almost 100% of drug was released from Viagra®. However, an in vivo experiment showed that the AEA-coated SDN–MMT exhibited higher drug exposure than Viagra®. For the AEA-coated SDN–MMT, the area under the plasma concentration– time curve from 0 hours to infinity (AUC0-∞) and maximum concentration (Cmax) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra® (AUC0-∞ = 69.2 ± 3.19 μg · hour/mL; Cmax = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure