Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa.

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription

Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice.

Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis

Machine Learning-Based Indoor Relative Humidity and CO2 Identification Using a Piecewise Autoregressive Exogenous Model: A Cob Prototype Study

The population of developed nations spends a significant amount of time indoors, and the implications of poor indoor air quality (IAQ) on human health are substantial. Many premature deaths attributed to exposure to indoor air pollutants result from diseases exacerbated by poor indoor air. CO2, one of these pollutants, is the most prevalent and often serves as an indicator of IAQ. Indoor CO2 concentrations can be significantly higher than outdoor levels due to human respiration and activity. The primary objective of this research was to numerically investigate the indoor relative humidity and CO2 in cob buildings through the CobBauge prototype, particularly during the first months following the building delivery. Both in situ experimental studies and numerical predictions using an artificial neural network were conducted for this purpose. The study presented the use of a piecewise autoregressive exogenous model (PWARX) for indoor relative humidity (RH) and CO2 content in a building constructed with a double walling system consisting of cob and light earth. The model was validated using experimental data collected over a 27-day period, during which indoor RH and CO2 levels were measured alongside external conditions. The results indicate that the PWARX model accurately predicted RH levels and categorized them into distinct states based on moisture content within materials and external conditions. However, while the model accurately predicted indoor CO2 levels, it faced challenges in finely classifying them due to the complex interplay of factors influencing CO2 levels in indoor environments

Monitoring of drying kinetics evolution and hygrothermal properties of new earth-based materials using climatic chamber simulation

This study focuses on the drying kinetics of cob and light-earth layers comprising a hybrid walling system. Volumetric water content sensors are immersed and placed at different positions on the walls of a building to measure the drying kinetics. In addition, an experimental analysis of the effect of temperature, relative humidity (RH), and wind velocity variations on thermal conductivity in a climatic chamber under winter and summer conditions was conducted. The analysis of samples in laboratory aims to investigate the hygrothermal properties of cob and light-earth materials, and their dependency on the aforementioned parameters. The in situ drying kinetics of both materials involves water content reduction and stabilization; however, in the laboratory, although the water content of materials decreases, the drying is incomplete. Which may be due to the limited wind speed. The hydrothermal properties show that open porosity affects water vapor permeability and modifies the RH of cob and light-earth. At 23 °C, when the relative humidity (RH) range was 10–30%, the absorbed water vapor of cob and light earth was 0–2%. However, when the RH is 40–90%, the absorbed water vapor of light earth (2–9%) exceeds that of cob (0.5–2%). Moreover, the response to relative humidity (RH) with regard to the mixing law of components and samples differs. The resistance factor to water vapor diffusion values for cob and light-earth are 12.9 and 8.2, respectively. In this study, the thermal conductivity measurements under summer and winter conditions provide the relationship between the thermal conductivity, density, and water content of cob and light-earth materials

Earth construction: Field variabilities and laboratory reproducibility

Building construction is a major polluting sector. As a result, there is increasing global interest in the development of sustainable building materials with low environmental impact. Earth-based materials are among the materials of interest and building with earth-based materials has thus received a particular renewal of attention. Previous research has focused on the physical characteristics and durability of these materials. The aim of this study is to assess the variability of materials made in-situ and their reproducibility in the laboratory using an automatic normal Proctor machine with different compaction energies. Both cob and light earth were investigated. Cylindrical and prismatic specimens were produced on-site and in the laboratory: cob was made of silt, silty clay, sandy silt, and flax straw; and a separate layer of light earth was made of elastic silt and reed fibres. An experimental program was designed to evaluate the properties of the materials in terms of their water content, density, porosity, compressive strength, and thermal conductivity. The results revealed that the in-situ densities could be reproduced in the laboratory with compaction energies of 0.6 MJ/m3 and 0.2 MJ/m3 for cob and light earth, respectively. These compaction energies will allow the research to produce laboratory specimens that were representative of the materials implemented on-site. Regarding the compressive strength, the values obtained in the laboratory were higher than those of the in-situ specimens. Correction factors of 0.88 and 0.67 for cob and light earth. These values should be applied to calibrate the laboratory results in relation to in-situ. Concerning the thermal conductivity, the values obtained in the laboratory were similar for cob and higher for light earth. A correction factor of 0.87 should be applied to calibrate the laboratory results to those obtained in-situ

Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

Vitamin E, the most important lipophilic radical scavenging antioxidant in vivo, has a pivotal role in brain. In an earlier study, we observed that adult mice with a defect in the gene encoding plasma phospholipid transfer protein (PLTP) display a moderate reduction in cerebral vitamin E levels, and exacerbated anxiety despite normal locomotion and memory functions. Here we sought to determine whether dietary vitamin E supplementation can modulate neurotransmitter levels and alleviate the increased anxiety phenotype of PLTP-deficient (PLTP−/−) mice. To address this question, a vitamin E-enriched diet was used, and two complementary approches were implemented: (i) “early supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice born from vitamin E-supplemented parents; and (ii) “late supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice fed a vitamin E-enriched diet from weaning. Our results show for the first time that an inadequate supply of vitamin E during development, due to moderate maternal vitamin E deficiency, is associated with reduced brain vitamin E levels at birth and irreversible alterations in brain glutamate levels. They also suggest this deficiency is associated with increased anxiety at adulthood. Thus, the present study leads to conclude on the importance of the micronutrient vitamin E during pregnancy

Insight into the Optimization of Implementation Time in Cob Construction: Field Test and Compressive Strength Versus Drying Kinetics

Mastering construction times is of paramount importance in making vernacular earth construction techniques attractive to modern clients. The work presented here is a contribution towards the optimization of the construction time of cob buildings. Therefore, this paper follows the evolution of a cob’s mechanical properties during its drying process in the case of a double-walling CobBauge system. Laboratory tests and in situ measurements were performed, and further results were described. Volumetric water content sensors were immersed in the walls of a CobBauge prototype building during its construction. The evolution of the cob layer’s compressive strength and Clegg Impact Value (CIV) as a function of its water content has been experimentally studied and discussed. These studies showed that compressive strength and CIV are correlated with water content, and both properties decrease exponentially with time. In this study, a new tool to evaluate cob’s mechanical performances in situ has been proposed, Clegg Impact Soil Tester. This was linked to compressive strength, and a linear relationship between these two properties was found. Finally, appropriate values of compressive strength and CIV to satisfy before formwork stripping and re-lifting were proposed. For this study’s conditions, these values are reached after approximately 27 days

RF Discharge Mirror Cleaning for ITER Optical Diagnostics Using 60 MHz Very High Frequency

For the fusion reactor ITER, a mandatory monitor of the fusion device and plasma will be performed with optical diagnostic systems. For the metallic first mirrors, the recovery of the reflectivity losses due to dust deposition is proposed to be carried out for 14 different optical diagnostic systems by the plasma cleaning technique. In this work, we studied the influence of the electrode area on the electrode potential as a function of the applied power with a 60 MHz radio very high frequency source. Unshielded copper disks with different diameters were constructed to study the impact of the electrode area in the range of 90 cm2 to 1200 cm2, which corresponds to an Edge Thomson Scattering area ratio of 0.15 to 2. It was observed that the absolute value of the resulting bias decreased from 280 V to 15 V with the increase of the area for a given RF power. Moreover, the power consumption was reduced by 43 langid = english, keywords = End-of-Cleaning indicator,First mirror,ITER,Plasma cleanin

Surface Modification of ITER-like Mirrors after One Hundred Cleaning Cycles Using Radio-Frequency Plasma

In ITER, the metallic first mirrors (FMs) will undergo erosion due to their proximity to the fusion plasma and deposition of materials originated from the first walls (mainly beryllium). In-situ plasma cleaning is a promising technique to conserve the FMs optical properties by means of ion sputtering. In this work, the evolution of the optical properties of single-crystal (Sc) and nanocrystalline (Nc) molybdenum (Mo) and rhodium (Rh) mirrors were investigated up to 100 cycles of consecutive contamination and cleaning. Aluminum oxide (AlO) was used as contaminant to replace the toxic beryllium. The plasma cleaning was carried out using a capacitively coupled argon (Ar) plasma excited by a 60 MHz radio-frequency generator resulting in the formation of a self-bias applied on the mirrors of -280 V. The plasma potential being around 30 V, the Ar ion energy was about 310 eV. The optical properties of the mirrors were assessed using ex-situ reflectivity measurements. Moreover, the surface topography was characterized by means of scanning electron microscopy (SEM), focused ion beam (FIB) and roughness measurements using atomic force microscopy (AFM). ScMo and ScRh mirrors formerly exposed to 80 successful cleaning cycles using aluminum/tungsten (Al/W) deposits and air storage exhibit drastic changes in their optical properties after being subject to cleaning cycles using AlO as contaminant. Additionally, freshly polished ScRh were exposed to identical cleaning cycles. All Sc mirrors exhibited pits induced by the polishing procedure using diamond paste in addition of mounds/wavy patterns. The carbon incorporated during the polishing process was demonstrated to be responsible for the pitting of the surface. The Nc mirrors preserved their initial reflectivities after up to 100 cycles. The surface topography was systematically characterized and an average erosion rate for NcRh mirrors of about 59 nm per cycle has been estimated from FIB cross-sections. The optical properties of the Nc mirrors showed a superiority in the present study in comparison to the Sc materials due to the influence of their polishin

Four-color multiplex real-Time PCR assay prototype targeting azithromycin resistance mutations in Mycoplasma genitalium

peer reviewedBackground: The worldwide expansion of macrolide-resistant Mycoplasma genitalium (MG) in cases of genital infections has led to an increased recurrence rate of these infections after first-line azithromycin treatment. By detecting the presence of azithromycin-resistant MG, the patient's antibiotic treatment can be targeted and the spread of resistance prevented. With this aim in mind, macrolide-resistance detection kits are helpful tools for the physician. Methods: Azithromycin resistance mutations in MG are targeted using a four-color multiplex real-Time RT-PCR assay. Tested targets include plasmid DNA (as positive controls) as well as macrolide-sensitive and macrolide-resistant genomic DNA from characterized cell lines and clinical samples. Results: The analytical data presented here were generated from plasmid DNA and genomic RNA/DNA and include adaptation to an internal control, specificity between targets, specificity vs non-MG species, limit of detection (LoD) and interference studies (co-infection and endogenous substances). The clinical data were based on the application of the assay to clinical samples characterized by sequencing. Conclusions: A new NAAT (nucleic acid amplification test) prototype has been developed in collaboration with the Diagenode s.a. company, this prototype targets MG and azithromycin-resistance mutations in that pathogen. © 2019 The Author(s)