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Background: Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial. Materials and methods: We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models. Results: We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (P = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (P = 0.38). We observed no difference in the pathological complete response rate between both groups. Conclusions: We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.

The enzyme lecithin:cholesterol acyl transferase has been measured both in total plasma and in the fraction of plasma from which very low and low density lipoproteins have been removed by ultracentrifugation. The correlation between the activity of the enzyme and the free cholesterol concentration was positive in whole plasma and negative in apoB-deficient plasma. On the other hand, the positive correlation between plasma triglycerides and cholesterol esterification was not changed by the removal of apoB-containing lipoproteins. Subjects with the highest levels of high density lipoprotein cholesterol were found to have the lowest enzyme activity, but this correlation was disclosed only in apoB-deficient plasma. This inverse relationship was abolished when the enzyme activity was measured in the absence of all lipoproteins with a density less than 1.125 g/ml. Cholesterol esterification, when determined after removal of lipoproteins with a density less than 1.063 g/ml, was negatively correlated with the in vivo plasma concentration of lipoproteins in the density range 1.063-1.125 g/ml. The same results were obtained in vitro by addition of increasing amounts of this class of high density lipoproteins either in total plasma or in the ultracentrifuged fractions of plasma. This provides further evidence that the lighter density class of high density lipoproteins inhibits the enzyme reaction under physiological conditions.

High resolution mass spectrometry (HRMS) can resolve thousands of compounds in complex mixtures such as natural organic matter. However, HRMS is seldom sufficient to fully resolve the molecular heterogeneity of Humus in the soil matrix, especially if no preliminary simplification of Humus complexity is applied and if a single ionization technique is used. Here we show that HRMS, when applied with both photoionization (APPI) and electrospray ionization (ESI) and combined with the extensive molecular simplification provided by a humeomic fractionation, significantly increases identification of the molecular composition of soil Humus. Different sequential extractions separate the soil Humeome in three organosoluble fractions (ORG1-3) and two hydrosoluble fractions (AQU2 and RESOM), which showed distinct molecular characteristics. The ORG fractions were particularly homogeneous and rich in alkyl compounds including unsaturated hydrocarbons and lipid compounds found mainly in ORG 1 and ORG 3, but also aromatic compounds comprising lignin-like molecules and condensed structures mainly detected in ORG2. The AQU2 fractions revealed greater complexity and heterogeneity due to the simultaneous detection of sugars, amino sugars, tannins and N-containing compounds not detectable in appreciable concentrations in other fractions. The most recalcitrant RESOM fraction contained highly reduced molecules and condensed structures. The combined use of APPI and ESI showed a marked selectivity in the detection of chemically different molecules separated in each fraction, thereby enhancing their molecular characterization. Specifically, APPI tended to ionize less oxidized and N-containing molecules, and compounds with high concentrations of unsaturation or aromatics, while ESI was more prone to detect highly oxidized compounds consisting of large O/C ratios. Our findings indicate that the combination of a soil Humeome fractionation with a detailed high resolution characterization of differently ionized molecules in the separated fractions enables a far deeper understanding of the molecular composition of soil Humus and the comprehension of its environmental reactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Three methods of membrane separation by dead-end, tangential, and centrifugal ultrafiltration (UF) were considered in order to understand the physicochemical phenomena occurring during the preconcentration of the colloidal phase of soil water. The analytical approach used involved dynamic light scattering (DLS), transmission electron microscopy (TEM), determination of total organic carbon (TOC-metry) and mass spectrometry (ICP-MS). The mass amounts of the major components of the colloidal phase, i.e. Al, Fe and total organic carbon (TOC), as well as the mass amount of uranium considered as a trace element of environmental interest, were determined, both in soil water, and in the concentrates (i.e. retentates) and filtrates of this water obtained by the 3 methods tested. Dead-end ultrafiltration led to an enlargement of the size distribution towards larger sizes because of agglomeration/aggregation phenomena. This method also generated enrichment of concentrates, in particular in organic matter. The consequence was that large structures were observed coating or embedding the particles initially present individually dispersed in the test sample. The mass amounts of elements and TOC increased more importantly than expected, which confirmed the enrichment of the concentrates from the dissolved phase probably by sorption on colloidal objects. To a lesser extent similar effects were observed after tangential ultrafiltration. Such phenomena were not observed after centrifugal ultrafiltration. From a practical point of view, both tangential and centrifugal ultrafiltration proved to be both the most practical and the best suited for the preconcentration of soil water sample. Finally, centrifugal ultrafiltration has proved to be the best compromise given the preservation of colloidal particles and method practicality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A comprehensive method for the determination and characterization of 15 common explosive compounds in water samples by ultra-high pressure liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) is presented. The method allows the determination of 10 nitroaromatics, two nitroamines and three nitrate ester compounds. Among these, 1,3,5-Triamino-2,4,6-trinitrobenzene (TATB) was quantified and detected for the first time in our knowledge at trace levels (0.2 µg/L). Furthermore, the collision induced dissociation (CID) mass spectrum of TATB is discussed and a fragmentation mechanism is proposed. The signal for each explosive was normalized by isotopically-enriched congeners used as internal standards. The limits of detection (LOD) reached 20 ng/L, depending on the type of energetic molecule, which are adequate for water samples and the linearity was verified from 1.4 to 2 orders of magnitude. The sensitivity of the UHPLC-APCI-MS/MS approach allows direct injection of aqueous samples without preceding extraction for concentration. Besides, the method displays a good reliability with low signal suppression in various matrices such as spring water, mineral water, acidified water or ground water. The effectiveness of the method is demonstrated by the analysis of underground water samples containing traces of explosives from test fields in France., (Copyright © 2015 Elsevier B.V. All rights reserved.)