Evaluation of chemical contamination of crops produced in greenhouse by irrigation with reclaimed water.

Using reclaimed water for agricultural irrigation is increasing worldwide to compensate for water scarcity. The aim of this work was to evaluate the uptake of some of the most commonly detected organic contaminants of emerging concern (CECs) and pesticides in regenerated water in a field study. Furthermore, it was studied their distribution and accumulation in the different parts of a crop (soil, plant and fruit). Three crops (cucumber, pepper and melon) were grown under controlled agronomic conditions in a greenhouse. In order to make an accurate evaluation of the process, "regenerated blank water" was spiked with 70 chemicals (including antibiotics, anti-inflammatories, analgesics, anaesthetics, anxiolytics, anticonvulsants, pesticides) at environmental concentrations (∼1 µg/L) and used for continuous crop irrigation. After crop season, the average total concentration of contaminants detected in the soil samples ranged from 132 to 232 µg/kg d.w depending of the crops type. Between 7 and 10 different contaminants were found in the harvested fruits, up to levels of 27.8 µg/kg f.w. cucumber, 12.4 µg/kg f.w. melon and 7.8 µg/kg f.w pepper. In general, cucumber fruit showed higher accumulation levels of contaminants than pepper and melon for most target analytes. The accumulation rates followed the order: root (0.2 %) < stem/leaf (1-4 %) < fruit (1-6 %) < soil (17-30 %). The experimental data obtained in this study were also used to assess the risk associated with the reuse of reclaimed water for crop irrigation as well to identify those contaminants that, due to their physicochemical properties, show higher accumulation rates and environmental impact.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Acetonitrile cluster solvation in a cryogenic ethane-methane-propane liquid: Implications for Titan lake chemistry.

The atmosphere of Titan, Saturn's largest moon, exhibits interesting UV- and radiation-driven chemistry between nitrogen and methane, resulting in dipolar, nitrile-containing molecules. The assembly and subsequent solvation of such molecules in the alkane lakes and seas found on the moon's surface are of particular interest for investigating the possibility of prebiotic chemistry in Titan's hydrophobic seas. Here we characterize the solvation of acetonitrile, a product of Titan's atmospheric radiation chemistry tentatively detected on Titan's surface [H. B. Niemann et al., Nature 438, 779-784 (2005)], in an alkane mixture estimated to match a postulated composition of the smaller lakes during cycles of active drying and rewetting. Molecular dynamics simulations are employed to determine the potential of mean force of acetonitrile (CH3CN) clusters moving from the alkane vapor into the bulk liquid. We find that the clusters prefer the alkane liquid to the vapor and do not dissociate in the bulk liquid. This opens up the possibility that acetonitrile-based microscopic polar chemistry may be possible in the otherwise nonpolar Titan lakes.

The Hanes-Woolf linear QUESP method improves the measurements of fast chemical exchange rates with CEST MRI.

PURPOSE: Contrast agents for chemical exchange saturation transfer MRI often require an accurate measurement of the chemical exchange rate. Many analysis methods have been reported that measure chemical exchange rates. Additional analysis methods were derived as part of this study. This report investigated the accuracy and precision of each analysis method. METHODS: Chemical exchange saturation transfer spectra were simulated using the Bloch-McConnell equations modified for chemical exchange. Chemical exchange saturation transfer spectra of iopromide were obtained with a range of saturation times, saturation powers, and concentrations. These simulated and experimental results were used to estimate the chemical exchange rate using the QUESP, QUEST, Omega Plot (LB-QUESP), EH-QUESP, HW-QUESP, LB-Conc, EH-Conc, and HW-Conc methods. RESULTS: Bloch fitting produced the most precise estimates of chemical exchange rates, although substantial expertise and computation time were required to achieve these results. Of the more simplistic analysis methods, the HW-QUESP method produced the most accurate and precise estimates of fast exchange rates. The QUEST and LB-QUESP methods produced the most accurate estimates of slow exchange rates, especially with samples that have short T(1w) relaxation times. CONCLUSIONS: HW-QUESP is a simplistic analysis method that should be used when fast chemical exchange rates need to be estimated from chemical exchange saturation transfer MRI results.

[Mucopenetrating nanoparticles: vehicles for the oral administration of paclitaxel]. / Nanoparticules mucopénétrantes: véhicules pour l'administration orale du paclitaxel.

Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.

Novel analysis of cation solvation using a graph theoretic approach.

A new method for analyzing molecular dynamics simulation data is employed to study the solvent shell structure and exchange processes of mono-, di-, and trivalent metal cations in water. The instantaneous coordination environment is characterized in terms of the coordinating waters' H-bonding network, orientations, mean residence times, and the polyhedral configuration. The graph-theory-based algorithm provides a rapid frame-by-frame identification of polyhedra and reveals fluctuations in the solvation shell shape--previously unexplored dynamic behavior that in many cases can be associated with the exchange reactions of water between the first and second solvation shells. Extended solvation structure is also analyzed graphically, revealing details of the hydrogen bonding network that have practical implications for connecting molecular dynamics data to ab initio cluster calculations. Although the individual analyses of water orientation, residence time, etc., are commonplace in the literature, their combination with graphical algorithms is new and provides added chemical insight.

MoleculaRnetworks: an integrated graph theoretic and data mining tool to explore solvent organization in molecular simulation.

This work discusses scripts for processing molecular simulations data written using the software package R: A Language and Environment for Statistical Computing. These scripts, named moleculaRnetworks, are intended for the geometric and solvent network analysis of aqueous solutes and can be extended to other H-bonded solvents. New algorithms, several of which are based on graph theory, that interrogate the solvent environment about a solute are presented and described. This includes a novel method for identifying the geometric shape adopted by the solvent in the immediate vicinity of the solute and an exploratory approach for describing H-bonding, both based on the PageRank algorithm of Google search fame. The moleculaRnetworks codes include a preprocessor, which distills simulation trajectories into physicochemical data arrays, and an interactive analysis script that enables statistical, trend, and correlation analysis, and other data mining. The goal of these scripts is to increase access to the wealth of structural and dynamical information that can be obtained from molecular simulations.

Intrinsic electronic transitions of the absorption spectrum of (OPy)2Ti(TAP)2: implications toward photostructural modifications.

Theoretical calculations based on time-dependent density functional theory are used to characterize the electronic absorption spectrum of a heteroleptic Ti-alkoxide molecule, (OPy)(2)Ti(TAP)(2) [OPy = pyridine carbinoxide, TAP = 2,4,6 tris(dimethylamino)phenoxide] under investigation as a photosensitive precursor for use in optically initiated solution synthesis of the metal oxide. Computational results support the assignment of UV absorption features observed in solid-state precursor films to key intrinsic ground-state transitions that involve ligand-to-metal charge transfer and pi-pi* transitions within the cyclic ligand moieties present. The nature of electron density redistribution associated with these transitions provides early insight into the excitation wavelength dependence of photostructural modification previously observed in this precursor system.

Correlation of calculated excited-state energies and experimental quantum yields of luminescent Tb(III) ß-diketonates.

Theoretical calculations employing time-dependent density functional theory (TDDFT) are used to characterize the excited states of Tb(III) ß-diketonate complexes. Calculated results are compared directly with experimental results that together show a correlation between relative quantum yields and the excited-state energies that depend on the electronic properties of the p,p'-substituent group associated with the coordinating N-donor neutral ligand. It is found that changes in the electron donating nature of the neutral ligand structure lead to shifts in the lowest triplet energy level of the complex that consequently change the relative quantum yield. This work provides critical direction for the synthesis of high quantum yield terbium complexes.

Characterization of the structural and electronic properties of crystalline lithium silicates.

Density functional theory (DFT) calculations within the generalized gradient approximation (GGA) were performed to study the atomic and electronic structure of lithium silicate crystals that were fully optimized within the theory. It is found that the relative stability of two crystalline forms of lithium disilicate agrees well with experimental results. The calculated electronic density of states shows distinguishable contributions to the oxygen 2s and upper valence bands associated with bridging (BO) and nonbridging oxygen (NBO) atoms. Bond ionicity, characterized by determining the relative atomic charges, is used to distinguish BO and NBO atoms as well as the corresponding Si-BO and Si-NBO bonds. Results from this work reveal that atomic charges obtained by using population analysis methods based on electron deformation density rather than total electron density provide an accurate description of bond ionicity consistent with chemical intuition.

Molecular mechanisms of hydrogen-loaded beta-hydroquinone clathrate.

Molecular dynamics simulations are used to investigate the molecular interactions of hydrogen-loaded beta-hydroquinone clathrate. It is found that, at lower temperatures, higher loadings are more stable, whereas at higher temperatures, lower loadings are more stable. Attractive forces between the guest and host molecules lead to a stabilized minimum-energy configuration at low temperatures. At higher temperatures, greater displacements take the system away from the shallow energy minimum, and the trend reverses. The nature of the cavity structure is nearly spherical for a loading of one, leads to preferential occupation near the hydroxyl ring crowns of the cavity with a loading of two, and at higher loadings, leads to occupation of the interstitial sites (the hydroxyl rings) between cages by a single H(2) molecule with the remaining molecules occupying the equatorial plane of the cavity. Occupation of the interstitial positions of the cavities leads to facile diffusion.

Structure, dynamics, and electronic properties of lithium disilicate melt and glass.

Ab initio molecular dynamics simulations within the framework of density functional theory have been performed to study the structural, dynamic, and electronic properties of lithium disilicate melt and the glass derived from quenching the melt. It is found that lithium ions have a much higher diffusion coefficient and show different diffusion mechanisms than the network forming silicon and oxygen ions in the melt. The simulated lithium disilicate glass structure has 100% four coordinated silicon, close to theoretical nonbridging oxygen to bridging oxygen ratio (2:3), and Q(n) distributions of 20.8%, 58.4%, and 20.8% for n=2,3,4, respectively. In the melt there are considerable amounts (10%-15%) of silicon coordination defects; however, the average silicon coordination number remains about 4, similar to that in the glass. The lithium ion coordination number increases from 3.7 in the glass to 4.4 in the melt mainly due to the increase of bridging oxygen in the first coordination shell. The bond length and bond angle distributions, vibrational density of states, and static structure factors of the simulated glass were determined where the latter was found to be in good agreement with experimental measurement. Atomic charges were obtained based on Bader and Hirshfeld population analyses [Atoms in Molecule: A Quantum Theory (Oxford University Press, Oxford, 1990); Theor. Chim. Acta 44, 129 (1977)]. The average Bader charges found in lithium disilicate glass were -1.729, 3.419, and 0.915 for oxygen, silicon, and lithium, respectively. The corresponding Hirshfeld charges were -0.307, 0.550, and 0.229. The electronic densities of states of the melt and glass were calculated and compared with those of crystalline lithium disilicate.

Molecular dynamic simulation of disorder induced amorphization in pyrochlore.

The defect accumulation mechanism of amorphization has been studied for the La2Zr2O7 pyrochlore by means of classical molecular dynamic simulations. Present calculations show that the accumulation of cation Frenkel pairs is the main driving parameter for the amorphization process, while the oxygen atoms simply rearrange around cations. Under Frenkel pair accumulation, the structure follows the pyrochlore-fluorite-amorphous sequence. Present results consequently provide atomic-level interpretation to previous experimental irradiation observations of the two-step phase transition.

Cleavage and recovery of molecular water in silica.

The network response associated with the incorporation and reactivity of water molecules in bulk phases of amorphous and crystalline silica are investigated using density functional theory. The extent of network relaxation is found to change the relative stabilities of the reactant and product states. A highly reactive site, with a low activation barrier, is associated with a highly strained site in which network relaxation significantly stabilizes the silanol state by effectively annealing the local structure. Diffusion and exchange reaction paths are found to likely be associated with minimum energy paths in which the stability of the product and reactant states are equal. These latter paths are associated with minimal network response, although the ability of the silanol groups to take on several conformations has an overall effect of changing the stability along a given reaction path.

Self-trapped excitons at the quartz(0001) surface.

We have studied self-trapped excitons in alpha-quartz using density functional theory (DFT), both in the crystal and at the (0001) surface. The excitons are triplet excited states that distort the crystal locally. They have a long lifetime, of the order of a millisecond, and become thermally equilibrated. We have calculated the drop in the exciton energy as it approaches the surface from the interior of the crystal. In the subsurface layer of the -OH terminated (0001) surface, the energy has dropped by 0.7 eV. Another 0.4 eV drop occurs as the exciton enters the surface layer, where it breaks off an OH radical. The drop in energy can be understood from the greater ease of structural distortion at the surface. These calculations illustrate that excitons formed in the bulk could migrate out to the surface and form chemically active surface species. Molecules adsorbed at the surface could also serve as traps for the excitons and could, in principle, be induced to undergo structural or chemical transitions.

Peroxidase antibody test for mucocutaneous leishmaniasis serology: performance index and comparison with a fluorescent antibody test

Os parâmetros sorológicos do teste de imunoperoxidase foram comparados aos do teste de imunofluorescência. O teste de imunoperoxidase mostrou ter sensibilidade e valor de prediçäo negativo estatisticamente mais alto que aqueles do teste de imunofluorescência porém, os limites de confiança 95% da especificidade e do valor de prediçäo positivo estavam contidos naqueles encontrados para o teste de imunofluorescência. Tais diferenças se mantiveram quando os cálculos dos índices foram feitos com e sem a inclusäo de soros de doença de Chagas ou leishmaniose visceral. A análise estatística mostrou que os dois testes tinham um grau substancial de concordância mas o teste de imunofluorescência tinha um índice de especificidade e o valor de prediçäo positivo igual a 100,0% quando os soros de Chagas e leishmaniose visceral foram excluídos. Neste caso, o teste positivo se torna o teste diagnóstico da doença em face da näo existência de falso-positivos. O conjugado de peroxidase poderá se constituir em fonte de problemas técnicos na sorologia se a relaçäo enzima/proteína se afastar das quantidades ótimas de marcaçäo

Statistical analysis of performance of a liquid chromatographic assay of anticonvulsants involving solvent-demixing extraction and reciprocal internal standardization.

Analysis of variance both factorial and nested was used to validate a HPLC method intended for routine clinical assay of ethosuximide, phenobarbital, phenytoin and carbamazepine. Drugs were salted out, together with the solvent, from 0.5 ml acetonitrile-deproteinized plasma samples with 80-90% recovery. The acetonitrile extraction solution contained a known amount of all four drugs. This added amount of any drug was used when absent from plasma as an internal standard for those present and when present as a calibrator. Results showed that assay precision was acceptable (CV 6%) over and above the therapeutic range when additions did not exceed the lower therapeutic plasma level and if as many replications were made as there were drugs to assay. In return for some loss of sensitivity, reciprocal internal standardization provides increased assay reliability owing to the usual availability of more than one internal standard and to easier identification of interfering chromatographic peaks.