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Paaske Randall opublikował 5 miesięcy, 1 tydzień temu
In this case-control study, we evaluated different quantitative parameters derived from routine multi-detector computed tomography (MDCT) scans with respect to their ability to predict incident osteoporotic vertebral fractures of the thoracolumbar spine.
16 patients who received baseline and follow-up contrast-enhanced MDCT and were diagnosed with an incident osteoporotic vertebral fracture at follow-up, and 16 age-, sex-, and follow-up-time-matched controls were included in the study. Vertebrae were labelled and segmented using a fully automated pipeline. Volumetric bone mineral density (vBMD), finite element analysis (FEA)-based failure load (FL) and failure displacement (FD), as well as 24 texture features were extracted from L1 – L3 and averaged. Odds ratios (OR) with 95% confidence intervals (CI), expressed per standard deviation decrease, receiver operating characteristic (ROC) area under the curve (AUC), as well as logistic regression models, including all analyzed parameters as independent variablerior for fracture risk assessment.
We used a structured approach to validate chemotherapy information derived from a national routinely collected chemotherapy dataset and from national administrative hospital data.
10,280 patients who had surgical resection with stage III colon cancer were included. First, we compared information derived from the national chemotherapy dataset (SACT) and from the administrative hospital dataset (HES) in the English NHS with respect to receipt of adjuvant chemotherapy (ACT). Second, we compared regimen and number of cycles in linked patient-level records. Third, we carried out a sensitivity analysis to establish to what extent the impact of ACT receipt differed according to data source.
6,012 patients (58 %) received ACT according to either dataset. Of these patients, 3,460 (58 %) had ACT records in both datasets, 1,649 (27 %) in SACT alone, and 903 (15 %) in HES alone. Of the 3,460 patients with records in both datasets, 3,320 (96 %) had matching regimens. There was good agreement on cycle number with simpture, particularly of oral chemotherapy from administrative hospital data, and to minimise bias.Some theories of spatial learning predict that associative rules apply under only limited circumstances. For example, learning based on a boundary has been claimed to be immune to cue competition effects because boundary information is the basis for the formation of a cognitive map, whilst landmark learning does not involve cognitive mapping. This is referred to as the cue type hypothesis. However, it has also been claimed that cue stability is a prerequisite for the formation of a cognitive map, meaning that whichever cue type was perceived as stable would enter a cognitive map and thus be immune to cue competition, while unstable cues will be subject to cue competition, regardless of cue type. In experiments 1 and 2 we manipulated the stability of boundary and landmark cues when learning the location of two hidden goals. One goal location was constant with respect to the boundary, and the other constant with respect to the landmark cues. For both cue types, the presence of distal orientation cues provided dment, following training in which both landmarks and boundary cues signalled two goal locations, a new goal location was established with respect to the landmark cues, before testing with the boundary, which had never been used to define the new goal location. The results of this novel test of the interaction between boundary and landmark cues indicated that new learning with respect to the landmark had a profound effect on navigation with respect to the boundary, counter to the predictions of incidental cognitive mapping of boundaries.One of the major concerns in the application of nanocarriers in biosensing is the impair of the recognition molecules bioactivity loaded on their surfaces due to harsh and laborious cross-linking and random orientation, resulting in unsatisfactory sensitivity. Herein, we proposed a novel immunochromatographic test strip (FNS-ag-DICTS) by taking advantage of the antigen (ag) modified Fe2O3 nanostructures (FNSs) as new signal tags and goat anti-mouse IgG labeling on the detection line instead of ag, which was used for sensitive detection of aflatoxin B1 (AFB1). The fabricated FNS-ag can orientate the Fab region of monoclonal antibodies (mAbs), waiving the intrinsic limitations of traditional nanomaterials labeled mAbs. Under optimal conditions, FNS-ag-DICTS possessed excellent specificity and a wide detection range, with a visual limit of detection (vLOD) of 0.0125 ng mL-1. In addition, the biosensor successfully detected AFB1 in peanut, green bean and corn, with an average recovery rate of 82.8-124.9%.
Excess lipid accumulation can accelerate the development of various metabolic diseases. Blossoms of Citrus aurantium L. var. amara Engl. (CAVA) have been reported to possess inhibitory capacities on lipid deposition. However, the constituents responsible for the observed bioactivity and the underlying mechanisms are still not clearly understood.
To screen constituents from blossoms of CAVA with inhibitory effects on lipid accumulation and to explore the action mechanism.
The chloroform (CHL) extracts are prepared from blossoms of CAVA by fractional extraction and are characterized using LC-MS assay. 3T3-L1 preadipocytes are induced with differentiation medium (DMI) and treated with CHL extracts. High fat diet (HFD)-induced obese mice are further established and administrated with CHL extracts for 12 weeks. Hematoxylin and eosin (HE) staining, Oil Red O staining, ELISA, RT-qPCR, western blot and 16S rRNA gene sequence methods are employed.
14 compounds are identified in CHL extracts and trigonelline hyss lipid accumulation through inhibiting differentiation of 3T3-L1 cells and attenuating metabolic syndromes in HFD-fed mice.
These findings suggest that CHL extracts probably suppress lipid accumulation through inhibiting differentiation of 3T3-L1 cells and attenuating metabolic syndromes in HFD-fed mice.Yunaconitine and indaconitine are active ingredients from the rhizomes of Aconitum plants. In this study, an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to measure the concentrations of the yunaconitine and indaconitine in mouse blood, and the method was applied in measuring the pharmacokinetics of the two alkaloids after oral and intravenous administration. A UPLC HSS T3 column (2.1 mm × 100 mm, 1.8 μm particle size) was used for chromatographic separation by gradient elution using acetonitrile-water (0.1% formic acid) as the mobile phase at a flow rate of 0.4 mL/min. Multiple reaction monitoring (MRM) mode and electrospray ionization (ESI) (positive-ion mode) were used to monitor the transitions of each analyte by tandem mass spectrometry for quantitative analysis. Yunaconitine and indaconitine were administered to the mice orally at 2 mg/kg and intravenously at 0.05 mg/kg. Blood was collected at various time intervals, and the blood samples were processed after collection and analyzed by UPLC-MS/MS. The standard curve generated for each analyte was linear over the concentration range of 0.5-500 ng/mL. The intra-day and inter-day accuracy of yunaconitine and indaconitine were 90%-103% and 86%-106%, respectively, and the precision (RSD, %) was less than 15% for both intra-day and inter-day measurements. The matrix effect ranged from 96% to 109%, and the recovery was higher than 72%. The UPLC-MS/MS method developed herein was successfully applied to measuring the pharmacokinetic parameters of yunaconitine and indaconitine in mice after intravenous and oral administration. The bioavailability of yunaconitine and indaconitine were 27.4% and 25.8%, respectively.Knowledge of the metabolic profile is essential for doping control analysis in sport since most drugs are excreted after an elaborate biotransformation process. Currently, Zebrafish Water Tank (ZWT) model has been applied to investigate the metabolism of different doping agents. Nevertheless, the class of glucocorticoids has not been subjected to this model for metabolism studies. In the present work, budesonide (BUD) was applied as a pilot to investigate the metabolic pathways of glucocorticoids in the ZWT model. The BUD biotransformation in ZWT model was compared to the described metabolism in humans. Samples from ZWT experiments were collected after BUD administration and analyzed by Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS). Following the identification and characterization of all significant metabolites described for humans, it was observed that the ZWT was able to produce in a relevant amount the main target for doping control purposes the 6β-hydroxy BUD. In addition, prior knowledge about the lack of butyrylcholinesterase activity in the zebrafish organism was considered for the evaluation for the formation of the 16α-hydroxy prednisolone, the most intense BUD metabolite in human urine. Biotransformation of BUD by ZWT focused on metabolites with the acetal fraction preserved, including the intermediate metabolite for the 16α-hydroxy prednisolone pathway. However,analternative metabolic pathway for the complete biotransformation of the 16α-hydroxy prednisolone intermediate was not observed, leading to the absence of the major human metabolite in the ZWT model. The findings reported in this study elucidate for the first time the application and limitations of the ZWT model to evaluate the metabolism of other glucocorticoids.Simultaneous determination of kynurenines, neurotransmitters, pterins and steroids linked to various neurological and metabolic diseases have important diagnostic significance for related pathology and drug monitoring. An improved, sensitive and selective ultra-high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometric (UHPLC-MS/MS) method, based on our earlier publication, has been proposed for the quantitative measurement of 42 metabolites in human urine. The assay covers a larger number of analytes, uses an advanced, Waters Atlantis T3 chromatographic column and similarly meets the guideline of European Medicines Agency (EMA) on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all > 0.998. Intra-day and inter-day accuracy and precision were 87-118%, 81-120% and 2-20%, respectively including the lower limit of quantification (LLOQ). The assay is expected to facilitate the diagnosis and allows drug level monitoring from urine.A novel magnetic nanocomposite of chitosan-grafted-poly(N-vinylcaprolactam) (Fe3O4/SiO2/CHT-g-PNVCL MNC) were synthesized. Chitosan was prepared from shrimp shells Penaeus monodon by a green deacetylation approach. N-vinylcaprolactam was first polymerized on the surface of Fe3O4 magnetic nanoparticles using surface-initiated atom transfer radical polymerization. Then, the Fe3O4 nanoparticles modified with carboxyl-terminated- poly(N-vinylcaprolactam) was grafted onto chitosan. Various techniques were used to characterize of physicochemical properties of synthesized nanomaterials. The application of Fe3O4/SiO2/CHT-g-PNVCL MNC was utilized as a novel adsorbent for the simultaneous extraction of trans-resveratrol and its major phase II metabolites from rat plasma. A qualitative analysis was performed using ultra-performance liquid chromatography triple-quadrupole tandem mass spectrometry. Response surface methodology based on central composite design was used to optimize the extraction procedure including pH, amount of adsorbent, extraction time, desorption time, and volume of elution solvent.