What's the best secondary treatment for patients who fail initial triple therapy for H pylori?

Q: What's the best secondary treatment for patients who fail initial triple therapy for H pylori? Evidence-based answer: treating patients with Helicobacter pylori infection who have failed clarithromycin-based triple therapy with either levofloxacin-based triple therapy (with amoxicillin and a proton pump inhibitor [PPI]) or a bismuth-based quadruple therapy produces cure rates of 75% to 81%. Ten-day regimens produce higher cure rates than 7-day regimens. Repeating the initial clarithromycin-based triple therapy cures fewer than half of patients (strength of recommendation [SOR]: A, meta-analyses of randomized controlled trials [RCTs]). Treating with a metronidazole-based triple therapy (with amoxicillin and a PPI) also produces high (87%) cure rates (SOR: A, meta-analyses of RCTs in exclusively Japanese populations). Selecting a secondary treatment regimen based on H pylori antibiotic susceptibility testing probably doesn't improve cure rates over empiric antibiotic treatment (SOR: B, meta-analyses of RCTs with conflicting results). However, after 2 treatment failures it may be necessary (SOR: C, expert opinion-based guidelines). Bismuth-based quadruple therapy has a more complex dosing regimen, and bismuth isn't available in some countries. Rising rates of H pylori resistance to levofloxacin in certain areas could make levofloxacin-based triple therapy less effective in the future (SOR: C, expert opinion-based guidelines).Leanne Jones, MD; Julien Ta, PharmD; Gary Kelsberg, MD (Valley Family Medicine Residency, University of Washington at Valley Medical Center, Renton) ; Sarah Safranek, MLIS (University of Washington Health Sciences Library, Seattle

Prediction of thermal radiative properties (300–1000 K) of La2NiO4+δ ceramics.

A multiscale numerical model is developed to predict the thermal radiative properties (TRP) of rough La2NiO4+δ coatings. The model integrates intrinsic and extrinsic contributions related to the chemical composition and the texture, respectively. High-temperature infrared reflectivity and thermogravimetric measurements on a La2NiO4+δ single crystal make it possible to understand the role of the excess oxygen in the intrinsic TRP. We show that dense ceramics with thicknesses higher than 4 μm are optically thick, and that one can adjust the surface roughness parameters to predict their TRP

Demonstration of relativistic electron beam focusing by a laser-plasma lens

Laser-plasma technology promises a drastic reduction of the size of high energy electron accelerators. It could make free electron lasers available to a broad scientific community, and push further the limits of electron accelerators for high energy physics. Furthermore the unique femtosecond nature of the source makes it a promising tool for the study of ultra-fast phenomena. However, applications are hindered by the lack of suitable lens to transport this kind of high-current electron beams, mainly due to their divergence. Here we show that this issue can be solved by using a laser-plasma lens, in which the field gradients are five order of magnitude larger than in conventional optics. We demonstrate a reduction of the divergence by nearly a factor of three, which should allow for an efficient coupling of the beam with a conventional beam transport line

Ultrafast filling of an electronic pseudogap in photoexcited (LaS) 1.196 VS 2

We investigate by angle and time resolved photoemission spectroscopy the unusual insulating state of strongly distorted triangular V slabs in (LaS)1.196VS2. We show that the electronic structure is dominated by the lowest band of the V t2g manifold, which disperses over 0.7 eV and is nearly filled. Hence, (LaS)1.196VS2 is not a Mott insulator. The spectra are strongly temperature dependent, shifting by 100 meV upon cooling to 50 K. The sudden photoexcitation at 50K induces a partial filling of the electronic pseudogap within less than 80 fs. The electronic energy flows into the lattice modes on a comparable timescale. We conclude that a very strong electron-phonon coupling makes this state extremely sensitive to small perturbations of the V clusters distortions

Assessment of Spatio-Temporal Changes of Land Use and Land Cover over South-Western African Basins and Their Relations with Variations of Discharges

West African basins play a vital role in the socio-economic development of the region. They are mostly trans-boundary and sources of different land use practices. This work attempts to assess the spatio-temporal land use and land cover changes over three South Western African basins (Volta, Mono and Sassandra basins) and their influence on discharge. The land use and land cover maps of each basin were developed for 1988, 2002 and 2016. The results show that all the studied basins present an increase in water bodies, built-up, agricultural land and a decline in vegetative areas. These increases in water bodies and land use are as a result of an increase in small reservoirs, of dugouts and of dam constructions. However, the decline in some vegetative clusters could be attributed to the demographic and socio-economic growth as expressed by the expansion of agriculture and urbanization. The basic statistical analysis of precipitation and discharge data reveals that the mean annual discharge varies much more than the total annual precipitation at the three basins. For instance, in the entire Volta basin, the annual precipitation coefficient of variation (CV) is 10% while the annual discharge CV of Nawuni, Saboba and Bui are 43.6%, 36.51% and 47.43%, respectively. In Mono basin, the annual precipitation CV is 11.5% while the Nangbeto and Athieme annual discharge CV are 37.15% and 46.60%, respectively. The annual precipitation CV in Sassandra basin is 7.64% while the annual discharge CV of Soubre and Dakpadou are 29.41% and 37%, respectively. The discharge varies at least three times much more than the precipitation in the studied basins. The same conclusion was found for all months except the driest months (December and January). We showed that this great variation in discharge is mainly due to land use and land cover changes. Beside the hydrological modification of the land use and land cover changes, the climate of the region as well as the water quality and availability and the hydropower generation may be impacted by these changes in land surfaces conditions. Therefore, these impacts should be further assessed to implement appropriate climate services and measures for a sustainable land use and water management

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy

Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2

The general transcription factor IIH (TFIIH) plays crucial roles in transcription as part of the pre-initiation complex (PIC) and in DNA repair as part of the nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3′-endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and structurally characterized the interaction between the Tfb1 subunit of TFIIH and Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several segments of the Rad2 spacer region yield yeast with enhanced sensitivity to UV irradiation. Isothermal titration calorimetry studies demonstrate that two acidic segments of the Rad2 spacer bind to Tfb1PH with nanomolar affinity. Structure determination of a Rad2–Tfb1PH complex indicates that Rad2 binds to TFIIH using a similar motif as TFIIEα uses to bind TFIIH in the PIC. Together, these results provide a mechanistic bridge between the role of TFIIH in transcription and DNA repair