Activity of N-Acetylcysteine Alone and in Combination with Colistin against Pseudomonas aeruginosa Biofilms and Transcriptomic Response to N-Acetylcysteine Exposure

Chronic colonization by Pseudomonas aeruginosa is critical in cystic fibrosis (CF) and other chronic lung diseases, contributing to disease progression. Biofilm growth and a propensity to evolve multidrug resistance phenotypes drastically limit the available therapeutic options. In this perspective, there has been growing interest in evaluating combination therapies, especially for drugs that can be administered by nebulization, which allows high drug concentrations to be reached at the site of infections while limiting systemic toxicity. Here, we investigated the potential antibiofilm activity of N-acetylcysteine (NAC) alone and in combination with colistin against a panel of P. aeruginosa strains (most of which are from CF patients) and the transcriptomic response of a P. aeruginosa CF strain to NAC exposure. NAC alone (8,000 mg/L) showed a limited and strain-dependent antibiofilm activity. Nonetheless, a relevant antibiofilm synergism of NAC-colistin combinations (NAC at 8,000 mg/L plus colistin at 2 to 32 mg/L) was observed with all strains. Synergism was also confirmed with the artificial sputum medium model. RNA sequencing of NAC-exposed planktonic cultures revealed that NAC (8,000 mg/L) mainly induced (i) a Zn21 starvation response (known to induce attenuation of P. aeruginosa virulence), (ii) downregulation of genes of the denitrification apparatus, and (iii) downregulation of flagellar biosynthesis pathway. NAC-mediated inhibition of P. aeruginosa denitrification pathway and flagellum-mediated motility were confirmed experimentally. These findings suggested that NAC-colistin combinations might contribute to the management of biofilm-associated P. aeruginosa lung infections. NAC might also have a role in reducing P. aeruginosa virulence, which could be relevant in the very early stages of lung colonization. © 2022 Valzano et al

In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 \ub5g/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability

Objective. The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. Method. In a multicenter study, a phantom with spheres of different diameters (6.5–57.4 mm) was filled with 18F-FDG at different target-to-background ratios (TBR: 2.5–70) and scanned for different acquisition periods (2–5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. Results. The goodness of the model fit was high (R2: 0.74–0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. Conclusions. Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration

Impact of amendments on the physical properties of soil under tropical long-term no till conditions

Tropical regions have been considered the world's primary agricultural frontier; however, some physico-chemical deficiencies, such as low soil organic matter content, poor soil structure, high erodibility, soil acidity, and aluminum toxicity, have affected their productive capacity. Lime and gypsum are commonly used to improve soil chemical fertility, but no information exists about the long-term effects of these products on the physical attributes and C protection mechanisms of highly weathered Oxisols. A field trial was conducted in a sandy clay loam (kaolinitic, thermic Typic Haplorthox) under a no-tillage system for 12 years. The trial consisted of four treatments: a control with no soil amendment application, the application of 2.1 Mg ha-1 phosphogypsum, the application of 2.0 Mg ha-1 lime, and the application of lime + phosphogypsum (2.0 + 2.1 Mg ha-1, respectively). Since the experiment was established in 2002, the rates have been applied three times (2002, 2004, and 2010). Surface liming effectively increased water-stable aggregates > 2.0 mm at a depth of up to 0.2 m; however, the association with phosphogypsum was considered a good strategy to improve the macroaggregate stability in subsoil layers (0.20 to 0.40 m). Consequently, both soil amendments applied together increased the mean weight diameter (MWD) and geometric mean diameter (GMD) in all soil layers, with increases of up to 118 and 89%, respectively, according to the soil layer. The formation and stabilization of larger aggregates contributed to a higher accumulation of total organic carbon (TOC) on these structures. In addition to TOC, the MWD and aggregate stability index were positively correlated with Ca2+ and Mg2+ levels and base saturation. Consequently, the increase observed in the aggregate size class resulted in a better organization of soil particles, increasing the macroporosity and reducing the soil bulk density and penetration resistance. Therefore, adequate soil chemical management plays a fundamental role in improving the soil's physical attributes in tropical areas under conservative management and highly affected by compaction caused by intensive farming

CoCoNet: towards coast to coast networks of marine protected areas (from the shore to the high and deep sea), coupled with sea-based wind energy potential

This volume contains the main results of the EC FP7 “The Ocean of Tomorrow” Project CoCoNet, divided in two sections: 1) a set of guidelines to design networks of Marine Protected Areas in the Mediterranean and the Black Seas; 2) a smart wind chart that will allow evaluating the possibility of installing Offshore Wind Farms in both seas. The concept of Cells of Ecosystem Functioning, based on connectivity, is introduced to define natural units of management and conservation. The definition of Good Environmental Status, as defined in the Marine Strategy Framework Directive, is fully embraced to set the objectives of the project, by adopting a holistic approach that integrates a full set of disciplines, ranging from physics to bio-ecology, economics, engineering and many sub-disciplines. The CoCoNet Consortium involved scientist sfrom 22 states, based in Africa, Asia, and Europe, contributing to build a coherent scientific community

Effects of gypsum and stubble retention on the chemical and physical properties of a sodic grey Vertosol in western Victoria

Copyright © 2001 CSIROThe effects of gypsum (0 and 10 t/ha) and stubble management [retained (SR) or burnt (SB)] on a range of soil chemical, physical, and micromorphological properties were investigated on a grey Vertosol soil near Natimuk, Victoria, Australia. After 2.5 years and 3 winter crops, gypsum, and to a lesser extent the stubble treatments, resulted in significant changes to the composition of the exchangeable and soluble cations, and to soil physical properties. When gypsum was combined with SR, the beneficial effects of this ameliorant on soil properties were present in both the A and B horizons of the soil. When combined with SB, the gypsum treatments were only effective in the A horizon. Organic carbon levels in the A and B horizons were not significantly affected by the gypsum or stubble treatments. However, micromorphological evidence indicated that in the A horizon, biological activity was greater in SR plots than SB plots. Soil dispersion, penetrometer resistance, and bulk density were reduced in plots treated with gypsum compared with plots without gypsum. A stubble management effect was also present, showing lower dispersion scores, penetrometer resistance values, and bulk densities in SR plots than SB plots. The available water holding capacity of the soil from Natimuk was significantly (P < 0.05) higher in the gypsum-treated plots than in plots without gypsum. This effect was limited to the A horizon of the SB plots, but was apparent for the A and B horizons of the plots treated with SR. The use of gypsum in combination with SR (and break crops) may improve soil physical and chemical properties at a greater depth than the use of gypsum with SB alone.F. P. Valzano, R. S. B. Greene, B. W. Murphy, P. Rengasamy and S. D. Jarwa

Best Practices for the 3D Documentation of the Grotta dei Cervi of Porto Badisco, Italy

The Grotta dei Cervi is a Neolithic cave where human presence has left many unique pictographs on the walls of many of its chambers. It was closed for conservation reasons soon after its discovery in 1970. It is for these reasons that a 3D documentation was started. Two sets of high resolution and detailed three-dimensional (3D) acquisitions were captured in 2005 and 2009 respectively, along with two-dimensional (2D) images. From this information a textured 3D model was produced for most of the 300-m long central corridor. Carbon dating of the guano used for the pictographs and environmental monitoring (Temperature, Relative humidity, and Radon) completed the project. This paper presents this project, some results obtained up to now, the best practice that has emerged from this work and a description of the processing pipeline that deals with more than 27 billions 3D coordinates.Peer reviewed: YesNRC publication: Ye

Pleuritis with pleural effusion due to a Bacillus megaterium infection

Pleural effusions may be related to pleuro-pulmonary or systemic disorders, including malignancy. Thoracentesis and thoracoscopy may be useful to diagnosis. In some cases, the diagnosis may be difficult and uncommon. We report the case of a hospitalized male for a pleuritis, with pleural effusion caused by a Bacillus megaterium infection, a Gram-positive, aerobic, spore-forming, and rod-shaped bacterium. To our knowledge, our case report is the first evidence of pleuritis due to B. megaterium. In the literature, up to now, B. megaterium infection has only been reported as involving the eye, skin, and brain

Pleuritis with pleural effusion due to a Bacillus megaterium

Pleural effusions may be related to pleuro-pulmonary or systemic disorders, including malignancy. Thoracentesis and thoracoscopy may be useful to diagnosis. In some cases, the diagnosis may be difficult and uncommon. We report the case of a hospitalized male for a pleuritis, with pleural effusion caused by a Bacillus megaterium infection, a Gram-positive, aerobic, spore-forming, and rod-shaped bacterium. To our knowledge, our case report is the first evidence of pleuritis due to B. megaterium. In the literature, up to now, B. megaterium infection has only been reported as involving the eye, skin, and brain