Carotid intima media thickness and blood biomarkers of atherosclerosis in patients after stroke or myocardial infarction

Aim To test if circulating levels of markers of inflammation, endothelial function, and chronic infections, as well as association between these markers and carotid intima media thickness (CIMT), depend on the stage of atherosclerosis expressed as a history of a major vascular event. Methods The associations were analyzed separately in 75 healthy controls, 79 patients 3-6 months after the first-ever non-cardioembolic ischemic stroke (IS), and 37 patients 3-6 months after the first-ever myocardial infarction (MI). Data were collected prospectively in 2005. We measured high sensitivity C-reactive protein (hs-CRP), procalcitonin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), serum level of immune complexes (IC), and identified antibodies against Herpes simplex virus type 1 (HSV), Cytomegalovirus, Chlamydia pneumonia, and Helicobacter pylori. Correlations with CIMT were determined using Pearson R and verified after adjustment for age, sex, hypertension, diabetes, and statin therapy. Results Median ICAM-1 concentration was significantly lower in controls than in post-IS patients (188 μg/L vs 215 μg/L), and significantly lower in post-IS patients than in post-MI patients (215 μg/L vs 260 μg/L). Control patients also had significantly lower IC level (0.03 U/L) and HSV antibody index (6.0) compared to both post-IS (0.6 U/L, 9.6) and post-MI (0.4 U/L, 9.2) patients. CIMT was correlated with age (Pearson R = 0.38, P = 0.001) in the control group, immune complexes (R = 0.26, P = 0.023) in the post-IS group, and with hs-CRP (R = 0.40, P = 0.017) in the post-MI group. These correlations were confirmed using multiple regression analysis. Conclusions Our study supports linear correlations between CIMT and IC and hs-CRP levels. However, these associations seem to depend on the type of vascular burden

Understanding the Origins of Bacterial Resistance to Aminoglycosides through Molecular Dynamics Mutational Study of the Ribosomal A-Site

Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493) in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations

Parametrization of 2-thiouracil and 4-thiouracil in CHARMM all-atom empirical force field

Abstract: A new set of force field parameters complementing the CHARMM27 all atom empirical force field for nucleic acids was developed for 2-thiouracil and 4-thiouracil, two naturally modified RNA bases. The new parameters allow for molecular modeling and molecular dynamics simulations of RNA containing 2-thiouracil and 4-thiouracil

Key Issues of Design and Investigations on Additive Manufactured Regular Cellular Structures

Celem niniejszej pracy jest przedstawienie wybranych aspektów związanych z projektowaniem i badaniem energochłonnych regularnych struktur komórkowych typu 2D wykonanych za pomocą addytywnych technik wytwarzania. Zaproponowana przez autorów metodyka badawcza obejmowała wytwarzanie struktur za pomocą dwóch technik druku 3D zróżnicowanych pod względem technologicznym i możliwości wytwórczych. Metoda FDM (ang. Fused Deposition Modelling) pozwoliła na przeanalizowanie procesu deformacji szerokiego spektrum topologii w zakresie obciążenia quasi-statycznego i udarowego. Z kolei metoda LENS (ang. Laser Engineered Net Shaping) umożliwiła wykonanie struktur ze stopu tytanu Ti6Al4V charakteryzującego się wysoką wytrzymałością mechaniczną. W pracy przedstawiono najważniejsze problemy związane z procesem badania regularnych struktur komórkowych w różnych warunkach obciążenia, w szczególności w warunkach dynamicznego odkształcenia z wykorzystaniem techniki dzielonego pręta Hopkinsona (SHPB). Przedstawiono główne zagadnienia związane z budową stanowiska SHPB oraz opisano specyfikę badania struktur komórkowych w klasycznym układzie prętów Hopkinsona i w układzie tzw. bezpośredniego uderzenia. Ponadto, dokonano obszernego omówienia problematyki modelowania numerycznego deformacji struktur komórkowych, ze szczególnym uwzględnieniem definicji założeń koniecznych do poprawnego ich zamodelowania.The aim of this paper is to present main issues concerning designing and investigation on 2D regular cellular structures produced using additive manufacturing techniques. Proposed by authors experimental methodology was based on two types of technologically different 3D printings methods with various manufacturing capabilities. FDM (Fused Deposition Modelling) technique allowed to analyze wide spectrum of structure topologies under static and impact loading conditions. LENS (Laser Engineered Net Shaping) method enabled to produce high strength structures made of titanium alloy Ti6Al4V. This paper presents the most important issues related to the testing process of the regular cellular structures under various loading conditions, in particular under dynamic deformation using the split Hopkinson pressure bar technique (SHPB). The main issues concerning the construction of SHPB experimental setup were presented as well as the specificity of the research methodology on cellular materials in two different Hopkinson bar systems: classic and so-called direct impact. In addition, the extensive discussions on numerical modelling of cellular structures deformation was made. In particular, the emphasis of assumptions necessary for their correct modelling was defined