Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of ...thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin.
This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention.
The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%;
=0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B (
=0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 95% CI, 0.7901-12.13;
=0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment (
=0.014).
The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I).
Bioresorbable vascular scaffolds (BVSs) have been studied in chronic coronary artery disease, but not in acute ST-segment elevation myocardial infarction (STEMI). This prospective multicentre study ...analysed the feasibility and safety of BVS implantation during primary percutaneous coronary intervention (p-PCI) in STEMI.
Bioresorbable vascular scaffold implantation became the default strategy for all consecutive STEMI patients between 15 December 2012 and 30 August 2013. A total of 142 patients underwent p-PCI; 41 of them (28.9%) fulfilled the inclusion/exclusion criteria for BVS implantation. The BVS device success was 98%, thrombolysis in myocardial infarction 3 flow was restored in 95% of patients, and acute scaffold recoil was 9.7%. An optical coherence tomography (OCT) substudy (21 patients) demonstrated excellent procedural results with only a 1.1% rate of scaffold strut malapposition. Edge dissections were present in a 38% of patients, but were small and clinically silent. Reference vessel diameter measured by quantitative coronary angiography was significantly lower than that measured by OCT by 0.29 (±0.56) mm, P = 0.028. Clinical outcomes were compared between BVS group and Control group; the latter was formed by patients who had implanted metallic stent and were in Killip Class I or II. Combined clinical endpoint was defined as death, myocardial infarction, or target vessel revascularization. Event-free survival was the same in both groups; 95% for BVS and 93% for Control group, P = 0.674.
Bioresorbable vascular scaffold implantation in acute STEMI is feasible and safe. The procedural results evaluated by angiography and OCT are excellent. The early clinical results are encouraging.
Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune ...response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim of the study is to analyze the relationship of plasma levels of TRP metabolites, inflammation, and OS in patients with neurovascular diseases (acute ischemic stroke (AIS), significant carotid artery stenosis (SCAS)) and in healthy controls. Blood samples were collected from 43 patients (25 with SCAS, 18 with AIS) and from 25 healthy controls. The concentrations of twelve TRP metabolites, riboflavin, neopterin (NEO, marker of inflammation), and malondialdehyde (MDA, marker of OS) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations of seven TRP metabolites (TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), anthranilic acid (AA), melatonin (MEL), tryptamine (TA)), NEO, and MDA were significantly different in the studied groups. Significantly lower concentrations of TRP, KYN, 3-HAA, MEL, TA, and higher MDA concentrations were found in AIS compared to SCAS patients. MDA concentration was higher in both AIS and SCAS group (
< 0.001,
= 0.004, respectively) compared to controls, NEO concentration was enhanced (
< 0.003) in AIS. MDA did not directly correlate with TRP metabolites in the study groups, except for 1) a negative correlation with kynurenine acid and 2) the activity of kynurenine aminotransferase in AIS patients (
= -0.552,
= 0.018;
= -0.504,
= 0.033, respectively). In summary, TRP metabolism is clearly more deregulated in AIS compared to SCAS patients; the effect of TRP metabolites on OS should be further elucidated.
The production of H13 tool steel (TS) by material extrusion (MEX) is a promising method in various applications, but as-built surface roughness does not comply with the quality requirements. Hence, ...this study investigated the effects of cutting parameters on tool wear, cutting forces, surface quality, microhardness, structure, and residual stresses when machining H13 TS produced by MEX. Dry machining (DM) proved advantageous in certain indicators such as tool wear and cutting forces in comparison to the flood cooling (FC). The lowest surface roughness (0.08 µm) was achieved at the cutting speed of 80 m/min, feed per tooth of 0.005 mm, and FC which corresponded to a 41 % decrease compared to DM under same conditions. Surface microhardness increased by 20 % after machining, decreasing with distance from the surface. The highest compressive residual stresses were observed under FC, while the DM resulted in a 78.2 % decrease in residual stresses due to a partial annealing effect caused by higher surface temperature. Overall, DM exhibited great potential for achieving high-quality surfaces with a favorable structure and residual stresses. This study´s novelty and robustness lie in its significant contribution to practical industrial applications, such as mold and core production.
•The tests carried out under the dry machining, resulted in lower tool wear than the flood cooling of the tool.•The higher cutting speed generated the higher cutting forces, which exhibited a linear dependence with cutting length.•The dry machining resulted with the lower surface roughness in all tests than tests performed with the flood cooling.
Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more ...important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events.
We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque.
This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques.
The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification.
Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.
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S1 nuclease from Aspergillus oryzae is a single‐strand‐specific nuclease from the S1/P1 family that is utilized in biochemistry and biotechnology. S1 nuclease is active on both RNA and DNA but with ...differing catalytic efficiencies. This study clarifies its catalytic properties using a thorough comparison of differences in the binding of RNA and DNA in the active site of S1 nuclease based on X‐ray structures, including two newly solved complexes of S1 nuclease with the products of RNA cleavage at atomic resolution. Conclusions derived from this comparison are valid for the whole S1/P1 nuclease family. For proper model building and refinement, multiple lattice‐translocation defects present in the measured diffraction data needed to be solved. Two different approaches were tested and compared. Correction of the measured intensities proved to be superior to the use of the dislocation model of asymmetric units with partial occupancy of individual chains. As the crystals suffered from multiple lattice translocations, equations for their correction were derived de novo. The presented approach to the correction of multiple lattice‐translocation defects may help to solve similar problems in the field of protein X‐ray crystallography.
Differences between the binding of RNA and DNA in S1 nuclease were analysed using X‐ray crystallography. In order to properly interpret the obtained diffraction data, a correction for multiple lattice‐translocation defects was applied.
During coagulation, the soluble fibrinogen is converted into insoluble fibrin. Fibrinogen is a multifunctional plasma protein, which is essential for hemostasis. Various oxidative posttranslational ...modifications influence fibrinogen structure as well as interactions between various partners in the coagulation process. The aim was to examine the effects of oxidative stress conditions on fibrin clot formation in arterial atherothrombotic disorders. We studied the changes in in vitro fibrin network formation in three groups of patients—with acute coronary syndrome (ACS), with significant carotid artery stenosis (SCAS), and with acute ischemic stroke (AIS), as well as a control group. The level of oxidative stress marker malondialdehyde measured by LC-MS/MS was higher in SCAS and AIS patients compared with controls. Turbidic methods revealed a higher final optical density and a prolonged lysis time in the clots of these patients. Electron microscopy was used to visualize changes in the in vitro-formed fibrin network. Fibers from patients with AIS were significantly thicker in comparison with control and ACS fibers. The number of fibrin fibers in patients with AIS was significantly lower in comparison with ACS and control groups. Thus, oxidative stress-mediated changes in fibrin clot formation, structure and dissolution may affect the effectiveness of thrombolytic therapy.
The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes ...of several strains of this Gram‐negative bacterium code for a FAD‐dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using SmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. SmTetX shares its fold with the tetracycline destructase TetX from Bacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.
Stenotrophomonas maltophilia codes for a tetracycline‐modifying FAD‐dependent monooxygenase that shares an overall fold with the tetracycline destructase TetX and possesses a unique active site within this enzyme family.
Incomplete stent apposition and uncovered struts are associated with a higher risk of stent thrombosis. No data exist on the process of neointimal coverage and late apposition status of the ...bioresorbable vascular scaffold (BVS) when implanted in the highly thrombogenic setting of ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to assess the serial changes in strut apposition and early neointimal coverage of the BVS using optical coherence tomography (OCT) in selected patients enrolled in the PRAGUE-19 study. Intracoronary OCT was performed in 50 patients at the end of primary percutaneous coronary intervention for acute STEMI. Repeated OCT of the implanted BVS was performed in 10 patients. Scaffold area, scaffold mean diameter and incomplete strut apposition (ISA) were compared between baseline and control OCT. Furthermore, strut neointimal coverage was assessed during the control OCT. Mean scaffold area and diameter did not change between the baseline and control OCT (8.59 vs. 9.06 mm
2
;
p
= 0.129 and 3.31 vs. 3.37 mm;
p
= 0.202, respectively). Differences were observed in ISA between the baseline and control OCT (0.63 vs. 1.47 %;
p
< 0.05). We observed 83.1 % covered struts in eight patients in whom the control OCT was performed 4–6 weeks after BVS implantation, and 100 % covered struts in two patients 6 months after BVS implantation. Persistent strut apposition and early neointimal coverage were observed after biodegradable vascular scaffold implantation in patients with acute ST-segment elevation myocardial infarction.
The aim of this study is to observe the effect of process parameters on residual stresses and relative density of Ti6Al4V samples produced by Selective Laser Melting. The investigated parameters were ...hatch laser power, hatch laser velocity, border laser velocity, high-temperature preheating and time delay. Residual stresses were evaluated by the bridge curvature method and relative density by the optical method. The effect of the observed process parameters was estimated by the design of experiment and surface response methods. It was found that for an effective residual stress reduction, the high preheating temperature was the most significant parameter. High preheating temperature also increased the relative density but caused changes in the chemical composition of Ti6Al4V unmelted powder. Chemical analysis proved that after one build job with high preheating temperature, oxygen and hydrogen content exceeded the ASTM B348 limits for Grade 5 titanium.
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