Does morphine administration affect ticagrelor conversion to its active metabolite in patients with acute myocardial infarction? A sub-analysis of the randomized, double-blind, placebo- -controlled IMPRESSION trial

Background. Therapy with aspirin and one of the platelet P2Y12 receptor inhibitors, preferably ticagrelor or prasugrel, is the mainstay of acute myocardial infarction (AMI) treatment. Morphine is the most commonly used analgesic in AMI patients. The IMPRESSION study was the first randomized trial to confirm that morphine use in this clinical setting leads to a delayed and attenuated exposure to ticagrelor and its active metabolite (AR-C124910XX). The mechanism underlying this drug-drug interaction remains hypothetical. Material and methods. A post hoc sub-analysis of the IMPRESSION study, a phase IV, single center, randomized, double-blind, placebo-controlled trial, was performed to examine whether morphine administration interferes with the proportion of AR-C124910XX produced from ticagrelor in AMI patients. Pharmacokinetic results of all subjects pretreated with placebo (n = 35) and morphine (n = 35) were analyzed. The ratio of total exposure to AR-C124910XX to total exposure to ticagrelor for 12 h was used to illustrate the rate of ticagrelor metabolism. Total exposure to investigated compounds was measured as the area under the plasma concentration-time curve (AUC). Results. The ratios of AUC(0–12) for AR-C124910XX to AUC(0–12) for ticagrelor were comparable between morphine and placebo pretreated patients (20.9 [13.9–34.6] v. 24.7 [18.1–29.6] %; p = 0.58). Importantly, visual inspection of the relationship between AUC(0–12) for AR-C124910XX and AUC(0–12) for ticagrelor revealed that regression lines for the morphine and placebo groups were located closely to each other, with a tendency for superimposing. Additionally, we observed similar values of slope coefficients for both study arms in the linear regression equations illustrating the relationship between AUC(0–12) for AR-C124910XX and AUC(0–12) for ticagrelor (0.19 [± 0.03] v. 0.21 [± 0.04]; p for the statistical significance of both slope coefficients < 0.0001). Conclusions. In the IMPRESSION study, conversion of ticagrelor to AR-C124910XX in AMI patients was not affected by morphine administration

National comparison of methods for determination of radon in water

The article describes three interlaboratory experiments concerning 222Rn determination in water samples. The fi rst two experiments were carried out with the use of artifi cial radon waters prepared by the Laboratory of Radiometric Expertise (LER), Institute of Nuclear Physics, Polish Academy of Sciences in Kraków in 2014 and 2018. The third experiment was performed using natural environment waters collected in the vicinity of the former uranium mine in Kowary in 2016. Most of the institutions performing radon in water measurements in Poland were gathered in the Polish Radon Centre Network, and they participated in the experiments. The goal of these exercises was to evaluate different measurement techniques used routinely in Polish laboratories and the laboratories’ profi ciency of radon in water measurements. In the experiment performed in 2018, the reference values of 222Rn concentration in water were calculated based on the method developed at LER. The participants’ results appeared to be worse for low radon concentration than for high radon concentrations. The conclusions drawn on that base indicated the weaknesses of the used methods and probably the sampling. The interlaboratory experiments, in term, can help to improve the participants’ skills and reliability of their results

Full-Field Strain Measurement and Numerical Analysis of a Microalloyed Steel Subjected to Deformation with Strain Path Change

This study presents an effective technique for taking advantage of the full-field measurement method of Digital Image Correlation (DIC) for the assessment of the strain distribution during the metal forming process when the strain path change was performed. The applied methodology is based on the combination of a numerical simulation for the stress calculation and full-field surface strain measurement in a forward/reverse three-point bending test. In the numerical part, the Chaboche model and dislocation density-based model were selected and verified in terms of the prediction of a softening/hardening effect occurring during strain reversal. The Chaboche model parameters identification procedure, on the basis of a cyclic torsion test, combined with inverse analysis, was also described. The results of the study showed the advantages and disadvantages of both of the analyzed work hardening models. The obtained results were analyzed in the light of the deformation inhomogeneity and reorganization of the dislocation structure during the cyclic deformation test

Experimental and Molecular Dynamic Study of Grain Refinement and Dislocation Substructure Evolution in HSLA and IF Steels after Severe Plastic Deformation

In this study, large-scale molecular dynamic simulations were performed to analyze the dislocation substructure interaction with various types of obstacles present in microalloyed steels during severe plastic deformation. Specifically, fully functional numerical models of the atomic upsetting test were developed, with particular emphasis on the presence of precipitates inside the microstructure grains. The obtained results compared with the microstructural tests, performed using Electron Backscatter Diffraction (EBSD) and Transmission Electron Microscope (TEM) techniques, allowed for a more accurate assessment of the microstructure refinement mechanisms by means of the in-situ recrystallization effect in the deformed samples subjected to the multi-axis compression using the MaxStrain system (Dynamic Systems Inc., New York, NY, USA)

How the Thermomechanical Processing Can Modify the High Strain Rate Mechanical Response of a Microalloyed Steel

The effects of thermomechanical processing (TMP) on the mechanical response of microalloyed steels subjected to dynamic loading conditions were examined. The deformation conditions in the thermomechanical laboratory rolling processes were selected on the basis of dilatometric tests. It allowed (with a constant value of total deformation) us to obtain microstructures with different compositions and morphology of the particular components. Several samples characterized by a particularly complex and unexpected representation of the obtained microstructures were selected for further research. Plastometric tests, i.e., compression and tensile tests, were performed under quasi-static loading with digital image correlation (DIC) analysis, and under dynamic loading on the Split Hopkinson Pressure Bar (SHPB) apparatus with strain rates of 1400 and 2000 s−1. Samples deformed in such conditions were subjected to microstructural analysis and hardness measurements. It has been observed that the use of various combinations of TMP parameters can result in the formation of specific microstructures, which in turn are the source of an attractive mechanical response under dynamic loading conditions. This opens up new possible areas of application for such popular structural materials which are microalloyed steels

Abiotrophia defectiva endocarditis – Diagnostic and therapeutic challenge: Case report

Belonging to the normal oral, gastrointestinal, and urogenital flora, Abiotrophia defectiva is responsible for 1–2 % of all infective endocarditis (IE) cases. The manifestation of A.defectiva endocarditis may by atypical, without fever. Difficult to isolate pathogen requires special culture media. A 45-year-old female was admitted due to anemia and progressive weight loss (8 kg in 6 months). She had a history of benign mitral valve (MV) prolapse and non-stenotic bicuspid aortic valve (BAV). In echocardiography, large vegetations on MV and small vegetation on BAV were found. An enriched medium for fastidious pathogens was used. A. defectiva was identified using biochemical analysis with VITEK-2 Compact. In the fourth week of antibiotic therapy, she required urgent MV replacement due to MV regurgitation progression while vegetation on BAV disappeared. Although patient's frailty and underweight caused prolonged postoperative wound healing, she was transferred to rehabilitation in good conditions. No relapse of IE was observed during five-month follow-up