Beneficial effects of nasal high flow oxygen therapy after weaning from non-invasive ventilation: A prospective observational study

It remains unknown whether application of nasal high flow (NHF) is effective after liberation from non-invasive ventilation (NIV). This study was aimed at investigating the effect of NHF in patients ready for weaning from NIV. With institutional ethic committee approval, patients receiving NIV due to hypoxemic respiratory failure for more than 24 hours were enrolled. After passing the weaning criteria with continuous positive airway pressure (CPAP) mode [fraction of inspiratory oxygen (FIO2) ≦0.5, positive end expiratory pressure (PEEP) 4 cmH2O], patients received NHF (Flow 50 L/min, FIO2 ≦0.5) immediately after liberation from NIV. Before the initiation of the study, eight sequential patients who received oxygen via face mask after NIV treatment, served as the historical control. Respiratory parameters [partial pressure of arterial oxygen (PaO2) to FIO2 ratio (P/F ratio), respiratory rate (RR)] 1 hour after liberation from NIV were evaluated with those during NIV as the primary outcome. The frequency of rescue NIV therapy, intubation, and respiratory failure were also recorded. Nine eligible patients received NHF therapy after liberation from NIV. P/F ratio and RR did not change significantly compared with those during NIV (231 ± 43.6 versus 250.7 ± 34.2 mmHg, 20.8 ± 2.3 versus 21 ± 1.6 /min), while P/F ratio decreased significantly in the historical control group (194.3 ± 20.1 versus 255.9 ± 58.1 mmHg, p=0.013). Rescue NIV therapy, intubation, and respiratory failure never occurred in the NFH group, although two patients received NIV rescue therapy, of whom one was intubated in the historical control. NHF after liberation from NIV might be effective in patients recovering from hypoxemic respiratory failure

Convenient modular method for affinity labeling (MoAL method) based on a catalytic amidation

金沢大学医薬保健研究域薬学系A modular methodology for affinity labeling, in which three essential elements generally constituting affinity probes are prepared separately as individual molecules, has been developed based on a catalytic amidation. © 2009 The Royal Society of Chemistry

Mycobacterium marinum Escapes from Phagosomes and Is Propelled by Actin-based Motility

Mycobacteria are responsible for a number of human and animal diseases and are classical intracellular pathogens, living inside macrophages rather than as free-living organisms during infection. Numerous intracellular pathogens, including Listeria monocytogenes, Shigella flexneri, and Rickettsia rickettsii, exploit the host cytoskeleton by using actin-based motility for cell to cell spread during infection. Here we show that Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of actively inducing actin polymerization within macrophages. M. marinum that polymerized actin were free in the cytoplasm and propelled by actin-based motility into adjacent cells. Immunofluorescence demonstrated the presence of host cytoskeletal proteins, including the Arp2/3 complex and vasodilator-stimulated phosphoprotein, throughout the actin tails. In contrast, Wiskott-Aldrich syndrome protein localized exclusively at the actin-polymerizing pole of M. marinum. These findings show that M. marinum can escape into the cytoplasm of infected macrophages, where it can recruit host cell cytoskeletal factors to induce actin polymerization leading to direct cell to cell spread

Atmospheric behaviors of particulate-bound polycyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons in Beijing, China from 2004 to 2010

Airborne particulates were collected at an urban site (site 1) from 2004 to 2010 and at a suburban site (site 2) in 2010 in Beijing. Nine polycyclic aromatic hydrocarbons (PAHs) and five nitropolycyclic aromatic hydrocarbons (NPAHs) in the airborne particulates were determined by HPLC with fluorescence and chemiluminescence detection, respectively. The concentrations of PAHs and NPAHs were higher in heating season than in non-heating season at the two sites. Both the concentrations of PAHs and NPAHs decreased in the non-heating season but only the concentrations of NPAHs decreased in heating season at site 1, from 2004 to 2010. These findings suggest that source control measures implemented by the city of Beijing helped to reduce air pollution in Beijing. The concentrations of PAHs increased at site 1 in 2010, possibly because of the transport of emissions from windward other areas, such as Shanxi province. Several diagnostic ratios of PAHs and NPAHs showed that the different sources contributed to Beijing\u27s air pollution, although coal combustion was the main source in the heating season and vehicle emission was the main source in the non-heating season. An analysis of physical parameters at Beijing showed that high wind speed can remove atmospheric PAHs and NPAHs in the heating season and that high relative humidity can remove them in the non-heating season. © 2017 Elsevier LtdEmbargo Period 12 month

Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene

Abstract: The carboxyl-terminal domain of RNA polymerase II (RNAP2) is phosphorylated during transcription in eukaryotic cells. While residue-specific phosphorylation has been mapped with exquisite spatial resolution along the 1D genome in a population of fixed cells using immunoprecipitation-based assays, the timing, kinetics, and spatial organization of phosphorylation along a single-copy gene have not yet been measured in living cells. Here, we achieve this by combining multi-color, single-molecule microscopy with fluorescent antibody-based probes that specifically bind to different phosphorylated forms of endogenous RNAP2 in living cells. Applying this methodology to a single-copy HIV-1 reporter gene provides live-cell evidence for heterogeneity in the distribution of RNAP2 along the length of the gene as well as Serine 5 phosphorylated RNAP2 clusters that remain separated in both space and time from nascent mRNA synthesis. Computational models determine that 5 to 40 RNAP2 cluster around the promoter during a typical transcriptional burst, with most phosphorylated at Serine 5 within 6 seconds of arrival and roughly half escaping the promoter in ~1.5 minutes. Taken together, our data provide live-cell support for the notion of efficient transcription clusters that transiently form around promoters and contain high concentrations of RNAP2 phosphorylated at Serine 5

Current Status of Large Helical Device and Its Prospect for Deuterium Experiment

Achievement of reactor relevant plasma condition in Helical type magnetic devices and exploration in its related plasma physics and fusion engineering are the aim of the Large Helical Device (LHD) project. In the recent experiments on LHD, we have achieved ion-temperature of 8.1 keV at 1 × 1019 m−3 by the optimization of wall conditioning using long pulse discharge by Ion Cyclotron Heating (ICH). The electron temperature of 10 keV at 1.6 × 1019 m−3 was also achieved by the optimization of Electron Cyclotron Heating (ECH). For further improvement in plasma performance, the upgrade of the Large Helical Device (LHD), including the deuterium experiment, is planned. In this paper, the recent achievements on LHD and the upgrade of LHD are described

Impurity emission characteristics of long pulse discharges in Large Helical Device

Line spectra from intrinsic impurity ions have been monitored during the three kinds of long-pulse discharges (ICH, ECH, NBI). Constant emission from the iron impurity shows no preferential accumulation of iron ion during the long-pulse operations. Stable Doppler ion temperature has been also measured from Fe XX, C V and C III spectra

Recent results from deuterium experiments on the large helical device and their contribution to fusion reactor development

In recent deuterium experiments on the large helical device (LHD), we succeeded in expanding the temperature domain to higher regions for both electron and ion temperatures. Suppression of the energetic particle driven resistive interchange mode (EIC) by a moderate electron temperature increase is a key technique to extend the high temperature domain of LHD plasmas. We found a clear isotope effect in the formation of the internal transport barrier in high temperature plasmas. A new technique to measure the hydrogen isotope fraction was developed in the LHD in order to investigate the behavior of the isotope mixing state. The technique revealed that the non-mixing and the mixing states of hydrogen isotopes can be realized in plasmas. In deuterium plasmas, we also succeeded in simultaneously realizing the formation of the edge transport barrier (ETB) and the divertor detachment. It is found that resonant magnetic perturbation plays an important role in the simultaneous formation of the ETB and the detachment. Contributions to fusion reactor development from the engineering point of view, i.e. negative-ion based neutral beam injector research and the mass balance study of tritium, are also discussed

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)

Background Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated. Methods We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations. Results Sixty-six patients in 48 families (33 males/females; 0-59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype-phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE. Conclusion This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.Genetics of disease, diagnosis and treatmen