Notes

Engaging do-it-yourself torture survivors from the worldwide combat personal.
Endogenous glycopeptides are significantly important in diverse pathological and physiological systems, but their direct analysis is severely hampered by their low abundance and presence of interfering species in biological fluids. In this study, we synthesized the amine-functionalized titanium metal-organic framework (NH2-MIL-125(Ti)) by a simple hydrothermal method, characterized and used for glycopeptides enrichment. The designed separation media is highly hydrophilic and stable which is suitable for hydrophilic interaction chromatography (HILIC). To make the process smooth, simple, reliable, and robust, NH2-MIL-125(Ti) crystals were packed in pipette-tip using hydrophilic melamine foam, as supporting frit. Free amine groups, present in the structure imparted hydrophilicity and a unique pattern of porosity, contributing to the size exclusion effect that excluded the large-sized proteins up to 1700 peptide to protein ratio. The prepared MOF particles possessed regular porosity, high surface area, good hydrophilicity, and offered an in-tip flow-based set-up enhanced the enrichment performance for N-linked glycopeptides. The affinity material showed a detection limit of 1 fmol.µL-1 and selectivity up to 11000 (HRP digest to BSA digest). Moreover, repeatability and reusability were evaluated up to five rounds of enrichment using the same affinity tip, and scanning electron microscopic images revealed no structural changes in the MOF crystals. Finally, the MOF packed in pipette tip was applied to selectively capture the N-linked endogenous glycopeptides from a healthy saliva sample and 64 unique endogenous glycopeptides were identified. These results demonstrated the excellent potential of NH2-MIL-125(Ti) based affinity tip for glycopeptides which can be used to enrich trace glycopeptide biomarkers from the biological fluids.To evaluate the endocannabinoid system in an animal model of Parkinson's disease, in-tube solid-phase microextraction (in-tube SPME) was directly coupled to a tandem mass spectrometry (MS/MS) system for determination of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples. In-tube SPME-which consisted of a microtube of restricted access material (RAM) with a hydrophilic diol external surface and a hydrophobic octyl inner surface-efficiently excluded (up to 95%) macromolecules from the biological samples and selectively pre-concentrated the analytes. In-tube SPME parameters, such as sample volume, mobile phases, flow rate, and pre-concentration time, were evaluated to improve the extraction efficiency and throughput performance. The selectivity of the in-tube SPME and MS/MS (MRM mode) techniques allowed them to be directly coupled online, which dismissed the need for the chromatographic separation step. The in-tube SPME-MS/MS method was validated and shown to be linear from 6.0 to 30.0 ng mL-1 for AEA and from 10.0 to 100.0 ng mL-1 for 2-AG; the intra- and inter-assay accuracy and precision were lower than 15%. Parallelism between the calibration curves constructed in the matrix and aqueous solution confirmed that there was no matrix effect. The method allowed endogenous concentrations of AEA and 2-AG to be determined in rat brain striatum from unilaterally 6-hydroxydopamine-lesioned animals. The concentrations of these endocannabinoids in striatum ipsilateral and contralateral to the lesion differed significantly (p less then 0.001).Lignocellulosic biomass is a promising resource of renewable energy. Its transformation to ethanol requires efficient pretreatment leading to complex liquid mixtures made of hundreds of oxygenated analytes. A large part of the released compounds belong to the carbohydrates family. Cytoskeletal Signaling inhibitor To overcome the complexity of such samples, a comprehensive on-line two-dimensional reversed-phase liquid chromatography hyphenated to high-resolution mass spectrometry (RPLC × RPLC-HRMS) was dedicated to the separation of carbohydrates and more specifically oligomers coming from pretreated lignocellulosic biomass. The first part of this study consisted in the optimization of such hyphenation (i.e. selection of stationary phases, mobile phases, sampling time, etc.). Then, the analytical method was applied to an industrial aqueous biomass product coming from the sulfuric acid-based pretreatment of a wheat straw. Around 70 well-resolved chromatographic peaks corresponding to oligomers were obtained. Occupation of the separation space between each chromatographic dimension was estimated to 75%. In the last part of this study, the interest of ion mobility-mass spectrometry in addition to RPLC × RPLC was discussed. Some examples highlighted the additional separation that can bring ion mobility to RPLC × RPLC-IMS-HRMS method. Using this four-dimensional hyphenation method, each analyte was described by two retention times, the collisional cross section and the molecular formula allowing to reach a level of detail never seen for biomass sample compositions.A novel magnetic solid-phase extraction (MSPE) material (Fe3O4@SiO2-NH2-G2) had been prepared and employed for adsorption and analysis of seven quaternary ammonium compounds (QACs) in infant fruit and vegetable products coupled with high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). In this paper, Fe3O4@SiO2-NH2-G2 was synthesized based on Fe3O4@SiO2-NH2 and dendrimer (G2) consisting of cyanuric chloride and imidazole. The morphology, configuration and magnetic behavior of the magnetic material were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). Critical parameters affecting extraction efficiency, such as the adsorbent amount, sample pH, extraction time, the type of eluent, and desorption time, were optimized. The proposed method provided good linearity with the correlation coefficients (R2) of 0.9992-0.9999, low limits of detection (LODs) (0.05-0.50 μg kg-1) and limits of quantitation (LOQs) (0.20-2.00 μg kg-1). The satisfactory method recoveries in three spiked infant fruit and vegetable products samples were between 80.12% and 101.35% with the relative standard deviations (RSDs) less than 12.04%. In summary, the established method was an effective sample preparation method and showed good prospect for the analysis of QACs in complex matrices.Cytokinins (CKs) are one class of important phytohormones widely investigated in most aspects of plant life. Similar to other phytohormones, CKs and their glycoconjugates are hydrophilic. Their ionization efficiencies for mass spectrometry (MS) detection are rather poor, whereas their retention and separation on reverse phase liquid chromatography (RPLC) are often unsatisfying. Chemical isotope labelling LC-MS analysis methods have been developed for most other phytohormones, enhancing their LC separations and quantitative sensitivity. However, there are currently no reports for chemical-labelled CKs. Here, we report a new chemical isotope labelling LC-MS analytical method for one-pot derivatization of CK bases and their glycoconjugates, based on differential benzylation labelling of the adenine skeleton of CKs with benzyl bromide and its deuterium isotope-labelled reagent. Benzylation alters the hydrophilicity of CKs and their glycoconjugates, improving their retention and separation on RPLC. The developed method demonstrated enhanced sensitivity, as the CKs and their glycoconjugates could be analysed with LODs within the range of 0.62-25.9 pg/mL. The method also demonstrated good intra- and inter-day precisions with standard deviations in the range of 1.9%-13.0%, and acceptable accuracy with recoveries in the range of 84.0%-119.9%. The developed method was employed on the quantitation of CKs in the fresh roots of Astragalus membranaceus collected from both fertilized and unfertilized fields. The significant impact that fertilizers had on endogenous CKs metabolism was observed. As such, monitoring endogenous CKs and their metabolites might be promising to control fertilizer abuse.
Despite treatment with radical cystectomy, patients with muscle invasive bladder cancer (MIBC) have a poor survival. It has been reported that survival is worse in NMIBC patients who progressed to MIBC in comparison to patients with de novo MIBC. The objective of this study was to compare survival of progressive versus de novo MIBC. Secondary objective was to explain this difference in survival by clinicopathological factors.

431 patients with MIBC who underwent radical cystectomy between 1998 and 2016 in the Radboudumc, Nijmegen, were retrospectively analyzed. 313 patients were identified with de novo MIBC and 118 with progressive MIBC.

5- and 10-year overall survival (OS) of patients with progressive MIBC was 37% and 20%, respectively. Patients with de novo MIBC had significantly better survival, with a 5- and 10-year OS of 49% and 39%, respectively. Patients with progressive MIBC were more frequently diagnosed with concomitant carcinoma in situ and positive surgical margins in bladder, ureters or urethra. In multivariable analysis that adjusted for these factors, progressive MIBC was associated with a hazard ratio of 1.40 (0.99 - 1.98). Kaplan-Meier survival curves show a detrimental effect of progressive MIBC in patients with pT2 versus pT3-4 tumors and in patients with negative versus positive surgical margins. In multivariable analysis, this effect modification disappeared.

Progressive MIBC is associated with poorer survival than de novo MIBC. Because most patients with progressive MIBC had a history of high risk NMIBC, considering radical cystectomy is most important in the highest risk NMIBC.
Progressive MIBC is associated with poorer survival than de novo MIBC. Because most patients with progressive MIBC had a history of high risk NMIBC, considering radical cystectomy is most important in the highest risk NMIBC.
With the introduction of new therapeutic options, the landscape of metastatic bladder cancer (mBC) management is shifting. We describe current clinical practice and outcomes of mBC patients as a benchmark for translation of developments into clinical practice in the near future.

Nation-wide population-based cohort study including all patients diagnosed with synchronous metastatic bladder cancer in the Netherlands in 2016-2017, identified through the Netherlands Cancer Registry (NCR). Clinical data on patient and disease characteristics, treatments and survival from the NCR were supplemented with specific information from electronic health records and descriptively analyzed. This study was part of the Prospective Bladder Cancer Infrastructure.

Synchronous metastatic bladder cancer was diagnosed in 636 patients in the Netherlands in 2016 and 2017. 35% (221 patients) received systemic treatment, of whom 88 received multiple treatment lines. Most common first-line regimen was carboplatin-based chemotherapy val corresponded relatively well with rates reported from trials among chemotherapy-treated patients. These data can serve as a benchmark for future studies evaluating the application of immunotherapy outside a trial setting.
To provide population-level estimates of the association of frailty with one-year outcomes after critical illness.

Retrospective cohort study of patients who survived an ICU admission between April 2002 and March 2015. Pre-existing frailty was classified using the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable Cox regression and Fine and Gray models were used to examine the association between frailty and mortality and hospital readmission.

Of 534,991 patients, 19.3% had pre-existing frailty. Compared to non-frail survivors, at one-year frail patients had higher mortality (18.3% vs 9.5%, adjusted HR 1.17 95% CI 1.15-1.19) and hospital readmission (44.4% vs 36.6%, adjusted HR 1.10 95% CI 1.08-1.11) and a CAN$19,628 (95% CI $19,279-$19,997) greater increase in healthcare costs compared to the year prior to hospitalization. The association between frailty and mortality was stronger among older individuals, but the risk of readmission among frail patients decreased with age.

Patients with pre-existing frailty who develop critical illness have higher rates of hospital readmission and death than patients without frailty, and age modifies these associations.
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