Nonlinear refraction in CH3NH3PbBr3 single crystals.

We measure both nonlinear absorption and nonlinear refraction in a ${{\rm CH}_3}{{\rm NH}_3}{{\rm PbBr}_3}$CH3NH3PbBr3 single crystal using the Z-scan technique with femtosecond laser pulses. At 1000 nm, we obtain values of 5.2 cm/GW and ${+}{9.5} \cdot {{10}^{ - 14}}\;{{\rm cm}^2}/{\rm W}$+9.5⋅10-14cm2/W for nonlinear absorption and nonlinear refraction, respectively. The sign and magnitude of the observed refractive nonlinearity are reproduced well by the two-band model. Our results suggest that the large nonlinear refractive index measured in perovskite nanostructures cannot be explained by an intrinsically high bound-electronic nonlinear refractive index in this emerging material class but is possibly caused by free carriers or quantum confinement effects.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood, and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients.

Evaluation of three MALDI-TOF mass spectrometry libraries for the identification of filamentous fungi in three clinical microbiology laboratories in Manitoba, Canada.

Matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) is commonly used by clinical microbiology laboratories to identify bacterial pathogens and yeasts, but not for the identification of moulds. Recent progress in extraction protocols and the composition of comparative libraries support potential application of MALDI-TOF MS for mould identification in clinical microbiology laboratories. We evaluated the performance of the Bruker Microflex™ MALDI-TOF MS instrument (Billerica, MA, USA) to identify clinical isolates and reference strains of moulds using 3 libraries, the Bruker mould library, the National Institutes of Health (NIH) library and the Mass Spectrometry Identification (MSI) online library, and compared those results to conventional (morphological) and molecular (18S/ITS; gold standard) identification methods. All 3 libraries demonstrated greater accuracy in genus identification (≥94.9%) than conventional methods (86.4%). MALDI-TOF MS identified 73.3% of isolates to species level compared to only 31.7% by conventional methods. The MSI library demonstrated the highest rate of species-level identification (72.0%) compared to NIH (19.5%) and Bruker (13.6%) libraries. Greater than 20% of moulds remained unidentified to species level by all 3 MALDI-TOF MS libraries primarily because of library limitations or imperfect spectra. The overall identification rate of each MALDI-TOF MS library depended on the number of species and the number of spectra representing each species in the library.

CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2.

CagA is a multifunctional toxin of Helicobacter pylori that is secreted into host epithelial cells by a type IV secretion system. Following host cell translocation, CagA interferes with various host-cell signalling pathways. Most notably this toxin is involved in the disruption of apical-basolateral cell polarity and cell adhesion, as well as in the induction of cell proliferation, migration and cell morphological changes. These are processes that also play an important role in epithelial-to-mesenchymal transition and cancer cell invasion. In fact, CagA is considered as the only known bacterial oncoprotein. The cellular effects are triggered by a variety of CagA activities including the inhibition of serine-threonine kinase Par1b/MARK2 and the activation of tyrosine phosphatase SHP-2. Additionally, CagA was described to affect the activity of Src family kinases and C-terminal Src kinase (Csk) suggesting that interference with multiple cellular kinase- and phosphatase-associated signalling pathways is a major function of CagA. Here, we describe the effect of CagA on protein kinase C-related kinase 2 (PRK2), which acts downstream of Rho GTPases and is known to affect cytoskeletal rearrangements and cell polarity. CagA interacts with PRK2 and inhibits its kinase activity. Because PRK2 has been linked to cytoskeletal rearrangements and establishment of cell polarity, we suggest that CagA may hijack PRK2 to further manipulate cancer-related signalling pathways.

Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation.

Lipopolysaccharide (LPS) is a major component on the surface of Gram negative bacteria and is composed of lipid A-core and the O antigen polysaccharide. O polysaccharides of the gastric pathogen Helicobacter pylori contain Lewis antigens, mimicking glycan structures produced by human cells. The interaction of Lewis antigens with human dendritic cells induces a modulation of the immune response, contributing to the H. pylori virulence. The amount and position of Lewis antigens in the LPS varies among H. pylori isolates, indicating an adaptation to the host. In contrast to most bacteria, the genes for H. pylori O antigen biosynthesis are spread throughout the chromosome, which likely contributed to the fact that the LPS assembly pathway remained uncharacterized. In this study, two enzymes typically involved in LPS biosynthesis were found encoded in the H. pylori genome; the initiating glycosyltransferase WecA, and the O antigen ligase WaaL. Fluorescence microscopy and analysis of LPS from H. pylori mutants revealed that WecA and WaaL are involved in LPS production. Activity of WecA was additionally demonstrated with complementation experiments in Escherichia coli. WaaL ligase activity was shown in vitro. Analysis of the H. pylori genome failed to detect a flippase typically involved in O antigen synthesis. Instead, we identified a homolog of a flippase involved in protein N-glycosylation in other bacteria, although this pathway is not present in H. pylori. This flippase named Wzk was essential for O antigen display in H. pylori and was able to transport various glycans in E. coli. Whereas the O antigen mutants showed normal swimming motility and injection of the toxin CagA into host cells, the uptake of DNA seemed to be affected. We conclude that H. pylori uses a novel LPS biosynthetic pathway, evolutionarily connected to bacterial protein N-glycosylation.

Scalable high-repetition-rate sub-half-cycle terahertz pulses from spatially indirect interband transitions.

Intense phase-locked terahertz (THz) pulses are the bedrock of THz lightwave electronics, where the carrier field creates a transient bias to control electrons on sub-cycle time scales. Key applications such as THz scanning tunnelling microscopy or electronic devices operating at optical clock rates call for ultimately short, almost unipolar waveforms, at megahertz (MHz) repetition rates. Here, we present a flexible and scalable scheme for the generation of strong phase-locked THz pulses based on shift currents in type-II-aligned epitaxial semiconductor heterostructures. The measured THz waveforms exhibit only 0.45 optical cycles at their centre frequency within the full width at half maximum of the intensity envelope, peak fields above 1.1 kV cm-1 and spectral components up to the mid-infrared, at a repetition rate of 4 MHz. The only positive half-cycle of this waveform exceeds all negative half-cycles by almost four times, which is unexpected from shift currents alone. Our detailed analysis reveals that local charging dynamics induces the pronounced positive THz-emission peak as electrons and holes approach charge neutrality after separation by the optical pump pulse, also enabling ultrabroadband operation. Our unipolar emitters mark a milestone for flexibly scalable, next-generation high-repetition-rate sources of intense and strongly asymmetric electric field transients.

Helicobacter pylori induces expression and secretion of oncostatin M in macrophages in vitro.

BACKGROUND: Helicobacter pylori is pathogenic bacterium that is associated with several gastric diseases in humans. Disease is characterized by severe inflammatory responses is the stomach that are induced by various chemokines and cytokines. Previous reports indicated that some of these responses are mediated through Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. METHODS: We performed JAK/STAT specific microarrays to identify new components of this signaling pathway, which are affected by Helicobacter pylori infection of THP-1 cells. RESULTS: We found that expression and secretion of oncostatin M and of its receptor were strongly up-regulated by Helicobacter pylori. OSM secretion was independent of CagA, VacA or Type IV secretion system. Helicobacter pylori culture supernatant induced OSM secretion. CONCLUSION: The induction of the pleiotropic cytokine oncostatin M suggests a possible role in Helicobacter pylori-mediated inflammation and diseases.

The complete genome sequence of Helicobacter pylori strain G27.

Helicobacter pylori is a gram-negative pathogen that colonizes the stomachs of over half the world's population and causes a spectrum of gastric diseases including gastritis, ulcers, and gastric carcinoma. The H. pylori species exhibits unusually high levels of genetic variation between strains. Here we announce the complete genome sequence of H. pylori strain G27, which has been used extensively in H. pylori research.

Pulmonary epithelial lining fluid concentrations after use of systemic amphotericin B lipid formulations.

Amphotericin B (AMB) concentrations were determined in pulmonary epithelial lining fluid (ELF) of 44 critically ill patients, who were receiving treatment with liposomal AMB (LAMB) (n = 11), AMB colloidal dispersion (ABCD) (n = 28), or AMB lipid complex (ABLC) (n = 5). Mean AMB levels (+/- standard errors of the means) in ELF amounted to 1.60 +/- 0.58, 0.38 +/- 0.07, and 1.29 +/- 0.71 microg/ml in LAMB-, ABCD-, and ABLC-treated patients, respectively (differences are not significant).

Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity.

Detergent-resistant membranes of eukaryotic cells are enriched in many important cellular signalling molecules and frequently targeted by bacterial pathogens. To learn more about pathogenic mechanisms of Helicobacter pylori and to elucidate novel effects on host epithelial cells, we investigated how bacterial co-cultivation changes the protein composition of detergent-resistant membranes of gastric adenocarcinoma (AGS) tissue culture cells. Using iTRAQ (isobaric tags for relative and absolute quantification) analysis we identified several cellular proteins, which are potentially related to H. pylori virulence. One of the proteins, which showed a significant infection-dependent increase in detergent resistance, was the polarity-associated serine/threonine kinase MARK2 (EMK1/Par-1b). We demonstrate that H. pylori causes the recruitment of MARK2 from the cytosol to the plasma membrane, where it colocalizes with the bacteria and interacts with CagA. Using Mardin Darby Canine Kidney (MDCK) monolayers and a three-dimensional MDCK tissue culture model we showed that association of CagA with MARK2 not only causes disruption of apical junctions, but also inhibition of tubulogenesis and cell differentiation.

Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells.

The serine/threonine kinase Par1 is a core component of the machinery that sets up polarity in the embryo and regulates cell fate decisions but its role in the homeostasis of adult tissues is poorly understood. Inhibition of Par1 by the bacterium Helicobacter pylori (H. pylori) represents the only established pathology that affects Par1 function in an adult epithelium. Thus, during chronic H. pylori infection of the gastric mucosa Par1 is one of the targets of the non-obligate H.pylori cytotoxic protein and oncogene CagA, which stimulates inflammation and triggers morphological changes, both believed to contribute to the gastric cancer risk imposed by H. pylori infection. Based on Par1's role in cell polarity, it has been speculated that Par1 inhibition affects epithelial polarity. Here we report the unexpected finding that CagA-mediated Par1-inhibition promotes the generation of DNA Double Strand Breaks in primary gastric epithelial cells, which likely contributes to the reported accumulation of mutations in chronically infected mucosal cells. Abbreviations: AGS: human gastric adenocarcinoma cell line; CM: CagA Multimerization (and Par1 binding) domain; H. pylori: Helicobacter pylori; DSB: Double Strand Break; HGECs: human (primary) gastric epithelial cells; IB: immunoblot; IF: immunofluorescence; MOI: Multiplicity of Infection; ROS: reactive oxygen species; Par1: Partitioning Defective 1 kinase; WT: wild type.

Correlation of optical properties and interface morphology in type-II semiconductor heterostructures.

(Ga,In)As/GaAs/Ga(As,Sb) and (Ga,In)As/GaAs/Ga(N,As) type-II double quantum well heterostructures have been grown by metal-organic vapor phase epitaxy. A growth interruption procedure was used to intentionally modify the morphology of the internal interfaces. The heterostructures were investigated using continuous wave and time-resolved photoluminescence as well as optical pump-optical probe spectroscopy. We find a correlation between the interface morphology and optical and kinetic properties. A growth interruption of about 120 s yielded substantially smoother interfaces both on vertical as well as lateral length scales. On the other hand a considerably enhanced type-II recombination time as well as a longer electron tunneling time are observed. We attribute this to a reduced interface localization in case of smoother interfaces.

Characteristics of neighborhood environment (social cohesion and safety) and common mental disorders in ELSA-Brasil study: a multilevel analysis.

The purpose of this study was to determine if self-reported characteristics of social cohesion and local neighborhood safety positively affect the mental health of their residents, regardless of individual characteristics. A sample of participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline was used. The Clinical Interview Schedule-Revised (CIS-R) instrument was used for tracking common mental disorders (CMD). Social cohesion and safety were measured by validated scales of neighborhood environment self-reported characteristics. The multilevel logistic regression model was used to estimate the effect in neighborhoods (level 2) and individuals (level 1), as well as the odds ratios for each neighborhood explanatory variable and social characteristics in the CMD. The results showed that part of the variance (2.3%), in the common mental disorders prevalence is attributed to local neighborhoods. The characteristics of social cohesion and safety remained significant, even after the adjustment of individual explanatory variables. This study confirmed the hypothesis that individuals living in neighborhoods where they perceive low social cohesion and safety present a higher chance of developing CMD.

Room-Temperature Stimulated Emission and Lasing in Recrystallized Cesium Lead Bromide Perovskite Thin Films.

Cesium lead halide perovskites are of interest for light-emitting diodes and lasers. So far, thin-films of CsPbX3 have typically afforded very low photoluminescence quantum yields (PL-QY < 20%) and amplified spontaneous emission (ASE) only at cryogenic temperatures, as defect related nonradiative recombination dominated at room temperature (RT). There is a current belief that, for efficient light emission from lead halide perovskites at RT, the charge carriers/excitons need to be confined on the nanometer scale, like in CsPbX3 nanoparticles (NPs). Here, thin films of cesium lead bromide, which show a high PL-QY of 68% and low-threshold ASE at RT, are presented. As-deposited layers are recrystallized by thermal imprint, which results in continuous films (100% coverage of the substrate), composed of large crystals with micrometer lateral extension. Using these layers, the first cesium lead bromide thin-film distributed feedback and vertical cavity surface emitting lasers with ultralow threshold at RT that do not rely on the use of NPs are demonstrated. It is foreseen that these results will have a broader impact beyond perovskite lasers and will advise a revision of the paradigm that efficient light emission from CsPbX3 perovskites can only be achieved with NPs.

CagA of Helicobacter pylori alters the expression and cellular distribution of host proteins involved in cell signaling.

To expand our knowledge of Helicobacter pylori virulence mechanisms, we used iTRAQ (isobaric tagging reagents for relative and absolute quantification)-based proteomic analysis to investigate the effect of H. pylori on gastric AGS tissue culture cells. In particular, we were interested in finding out which effects of H. pylori were dependent on the cytotoxins CagA and VacA. Protein analysis was restricted to detergent-resistant membranes (DRMs), because both toxins were described previously to localize in lipid raft-like domains. Using H. pylori wild type and two isogenic mutants, DeltacagA and DeltavacA, we identified a total of 21 proteins that were either increased or decreased in the DRMs due to bacterial infection. The effect on three of these proteins, ezrin, syndecan-4 and Rab11-FIP1, were furthermore dependent on CagA. Because these proteins have been implicated in cell migration, adhesion and polarity, they might act as important mediators of CagA cytotoxicity.

Reliability of diagnoses coding with ICD-10.

OBJECTIVE: Reliability of diagnoses coding is essential for the use of routine data in a national health care system. The present investigation compares reliability of diagnoses coding with ICD-10 between three groups of coding subjects. METHOD: One hundred and eighteen students coded 15 diagnoses lists, 27 medical managers from hospitals 34 discharge letters, and 13 coding specialists 12 discharge letters. Agreement in principal diagnosis was assessed using Cohen's Kappa and the fraction of coincidences over the number of pairs, agreement for the full set of diagnoses with a previously developed measure p(om). RESULTS: Kappa values were fair (managers) or moderate (coders) for terminal codes with 0.27 and 0.42 (agreement 29.2% versus 46.8%), substantial for the chapter level with 0.71 and 0.72 (agreement 78.3% versus 80.8%). p(om) was lower for the full set of diagnoses than for principal diagnoses, for example in case of managers with 0.21 versus 0.29 for terminal codes. Best results were achieved by students coding diagnoses lists. In summary, the results are remarkably lower than in earlier publications. CONCLUSION: The refinement of the ICD-10 accompanied by innumerous coding rules has established a complex environment that leads to significant uncertainties even for experts. Use of coded data for quality management, health care financing, and health care policy requires a remarkable simplification of ICD-10 to receive a valid image of health care reality.

Tolerability of inhaled N-chlorotaurine in humans: a double-blind randomized phase I clinical study.

BACKGROUND: N-chlorotaurine (NCT), a long-lived oxidant produced by human leukocytes, can be synthesized chemically and used topically as a well-tolerated antiseptic to different body regions including sensitive ones. The aim of this study was to test the tolerability of inhaled 1% NCT in aqueous solution upon repeated application. METHODS: The study was performed double-blind and randomized with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). There were two Austrian centres involved, the hospitals, Natters and Vöcklabruck. Healthy, full age volunteers were included, 12 in each centre. A total of 12 patients were treated with NCT, and 12 with placebo, exactly half of each group from each centre. The single dose was 1.2 ml inhaled over a period of 10 min using an AKITA JET nebulizer. One inhalation was done every day for five consecutive days. The primary criterion of evaluation was the forced expiratory volume in 1 second (FEV1). Secondary criteria were subjective sensations, further lung function parameters such as airway resistance, physical examination, and blood analyses (gases, electrolytes, organ function values, pharmacokinetic parameters taurine and methionine, immune parameters). RESULTS: All included 15 females and 9 males completed the treatment and the control examinations according to the study protocol. FEV1 (100.83% ± 8.04% for NCT and 92.92% ± 11.35% for controls) remained unchanged and constant during the treatment and in control examinations 1 week and 3 months after the treatment (98.75% ± 7.37% for NCT and 91.17% ± 9.46% for controls, p > 0.082 between time points within each group). The same was true for all other objective parameters. Subjective mild sensations with a higher frequency in the test group were chlorine taste ( p < 0.01) and occasional tickle in the throat ( p = 0.057). Taurine and methionine plasma concentrations did not change within 60 min after inhalation or later on. CONCLUSIONS: Inhaled NCT is well tolerated as in other applications of different body regions. Side effects are mild, topical and transitory. The study was registered prospectively in the European Clinical Trials Database of the European Medicines Agency. The EudraCT number is 2012-003700-12.

[Non-invasive and invasive out of hospital ventilation in chronic respiratory failure : Consensus report of the working group on ventilation and intensive care medicine of the Austrian Society of Pneumology]. / Nichtinvasive und invasive außerklinische Beatmung beim chronisch respiratorischen Versagen : Konsensus-Report des Arbeitskreises für Beatmung & Intensivmedizin der Österreichischen Gesellschaft für Pneumologie.

The current consensus report was compiled under the patronage of the Austrian Society of Pneumology (Österreichischen Gesellschaft für Pneumologie, ÖGP) with the intention of providing practical guidelines for out-of-hospital ventilation that are in accordance with specific Austrian framework parameters and legal foundations. The guidelines are oriented toward a 2004 consensus ÖGP recommendation concerning the setup of long-term ventilated patients and the 2010 German Respiratory Society S2 guidelines on noninvasive and invasive ventilation of chronic respiratory insufficiency, adapted to national experiences and updated according to recent literature. In 11 chapters, the initiation, adjustment, and monitoring of out-of-hospital ventilation is described, as is the technical equipment and airway access. Additionally, the different indications-such as chronic obstructive pulmonary diseases, thoracic restrictive and neuromuscular diseases, obesity hypoventilation syndrome, and pediatric diseases-are discussed. Furthermore, the respiratory physiotherapy of adults and children on invasive and noninvasive long-term ventilation is addressed in detail.