Prediction of recurrent ventricular arrhythmia (VA) in survivors of an out-of-hospital cardiac arrest (OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of ...myocardial scarring assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to characterize myocardial scarring as defined by LGE-CMR in survivors of a VA-OHCA and investigate its potential role in the risk of new VA events.
Between 2015 and 2022, a total of 230 VA-OHCA patients without ST-segment elevation myocardial infarction had CMR before implantable cardioverter-defibrillator implantation for secondary prevention at Copenhagen University Hospital, Rigshospitalet, and Hospital Clínic, University of Barcelona, of which n = 170 patients had a conventional (no LGE protocol) CMR and n = 60 patients had LGE-CMR (including LGE protocol). Scar tissue including core, border zone (BZ) and BZ channels were automatically detected by specialized investigational software in patients with LGE-CMR. The primary endpoint was recurrent VA.
After exclusion, n = 52 VA-OHCA patients with LGE-CMR and a mean left ventricular ejection fraction of 49 ± 16% were included, of which 18 (32%) patients reached the primary endpoint of VA. Patients with recurrent VA in exhibited greater scar mass, core mass, BZ mass, and presence of BZ channels compared with patients without recurrent VA. The presence of BZ channels identified patients with recurrent VA with 67% sensitivity and 85% specificity (area under the ROC curve (AUC) 0.76; 95% CI: 0.63-0.89; p < .001) and was the strongest predictor of the primary endpoint.
The presence of BZ channels was the strongest predictor of recurrent VA in patients with an out of-hospital cardiac arrest and LGE-CMR.
To explore the genetic landscape of tumors from patients enrolled on the BOLERO-2 trial to identify potential correlations between genetic alterations and efficacy of everolimus treatment. The ...BOLERO-2 trial has previously demonstrated that the addition of everolimus to exemestane prolonged progression-free survival by more than twofold in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer previously treated with nonsteroidal aromatase inhibitors.
Next-generation sequencing was used to analyze genetic status of cancer-related genes in 302 archival tumor specimens from patients representative of the BOLERO-2 study population. Correlations between the most common somatic alterations and degree of chromosomal instability, and treatment effect of everolimus were investigated.
Progression-free survival benefit with everolimus was maintained regardless of alteration status of PIK3CA, FGFR1, and CCND1 or the pathways of which they are components. However, quantitative differences in everolimus benefit were observed between patient subgroups defined by the exon-specific mutations in PIK3CA (exon 20 v 9) or by different degrees of chromosomal instability in the tumor tissues.
The data from this exploratory analysis suggest that the efficacy of everolimus was largely independent of the most commonly altered genes or pathways in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The potential impact of chromosomal instabilities and low-frequency genetic alterations on everolimus efficacy warrants further investigation.
Retinoic acid inducible gene-I (RIG-I) is an innate RNA sensor that recognizes the influenza A virus (IAV) RNA genome and activates antiviral host responses. Here, we demonstrate that RIG-I signaling ...plays a crucial role in restricting IAV tropism and regulating host immune responses. Mice deficient in the RIG-I-MAVS pathway show defects in migratory dendritic cell (DC) activation, viral antigen presentation, and priming of CD8+ and CD4+ T cell responses during IAV infection. These defects result in decreased frequency of polyfunctional effector T cells and lowered protection against heterologous IAV challenge. In addition, our data show that RIG-I activation is essential for protecting epithelial cells and hematopoietic cells from IAV infection. These diverse effects of RIG-I signaling are likely imparted by the actions of type I interferon (IFN), as addition of exogenous type I IFN is sufficient to overcome the defects in antigen presentation by RIG-I deficient BMDC. Moreover, the in vivo T cell defects in RIG-I deficient mice can be overcome by the activation of MDA5 -MAVS via poly I:C treatment. Taken together, these findings demonstrate that RIG-I signaling through MAVS is critical for determining the quality of polyfunctional T cell responses against IAV and for providing protection against subsequent infection from heterologous or novel pandemic IAV strains.
This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies.
...Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy.
In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were randomly assigned to a group receiving enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (LVEF).
The mean age of patients was 50 ± 13 years old, and 43% were women. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a -3.1% absolute difference by echocardiography (p = 0.035) and -3.4% (p = 0.09) in the 59 patients who underwent CMR. The corresponding absolute difference (95% confidence interval CI) in LVEF was -6.38% (95% CI: -11.9 to -0.9) in patients with acute leukemia and -1.0% (95% CI: -4.5 to 2.5) in patients undergoing autologous HSCT (p = 0.08 for interaction between treatment effect and disease category). Compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02).
Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger studies. (Prevention of Left Ventricular Dysfunction During Chemotherapy OVERCOME; NCT01110824).
An investigation of the mechanical properties of high-purity niobium single crystals is presented. Specimens were cut with different crystallographic orientations from a large grain niobium disk and ...uniaxial tensile tests were conducted at strain rates between 10-4 and 103 s-1. The logarithmic strain rate sensitivity for crystals oriented close to the center of a tensile axis inverse pole figure (IPF) is ~0.14 for all strain rates. The strain at failure (ranging from 0.4 to 0.9) is very sensitive to crystal orientation and maximal at ~10-2 s-1 for crystals oriented close to the center of an IPF. The high anisotropy observed at quasi-static strain rates decreased with increasing strain rate. The activation of multiple slip systems in the dynamic tests could account for this reduction in anisotropy. A transition from strain hardening to softening in the plastic domain was observed at strain rates greater than approximately 6 × 10-2 s-1 for crystals oriented close to the center of a tensile axis IPF. Shear bands were observed in specimens with orientations having similarly high Schmid factors on both {110}and {112}slip families, and they are correlated with reduced ductility. Crystal rotations at fracture are compared for the different orientations using scanning electron microscopy images and EBSD orientation maps. A rotation toward the terminal stable 101 orientation was measured for the majority of specimens (with tensile axes more than ~17° from the 001 direction) at strain rates between 1.28 × 10-2 and 1000 s-1.
► Emulsifiers, enzymes and hydrocolloids were used to produce gluten-free breads. ► Rheological and calorimetric properties of gluten-free doughs were evaluated. ► Additives modified dough ...properties, but final bread quality was not improved. ► Additives are not essential for gluten free bread production. ► Ingredients’ specific interactions seem to govern the system’s behavior.
The objective of this work was to assess the effect of emulsifiers, hydrocolloids and enzymes on gluten-free dough rheology and thermal properties and bread quality, while relating dough properties parameters to bread technological quality. Breads were based on rice flour, cassava starch and full-fat active soy flour, with 65% or 75% (flour-starch basis) of water incorporation. Additives used were emulsifiers (diacetyl tartaric acid ester of monoglycerides – DATEM and sodium stearoyl lactylate – SSL), enzymes (glucose oxidase and α-amylase) and hydrocolloids (xanthan gum, carboxymethylcellulose, alginate and carrageenan). Results showed that additive incorporation modified dough behavior, evidenced by different calorimetric and rheological properties. Besides, the electrophoretic pattern of dough extracted proteins changed with glucose oxidase addition. These modifications resulted in breads with different characteristics, such as specific volume, firmness and firming rate, and crumb structure. Nonetheless, they did not necessarily show better quality parameters than the control bread. The control dough displayed good performance for obtaining gluten-free breads of acceptable volume, crumb structure and, principally, with lower hardening rate during storage. Contrary to widespread opinion, this work shows that the presence of additives is not essential for gluten-free bread production. This fact provides new perspectives to the gluten free market at the moment of selecting raw materials and technological parameters, reducing production costs and facilitating gluten free products development.
The in electrical vehicles, where the electric motor is inside the transmissielectrical compatibility of the automatic transmission fluids (ATFs) is very important on and in contact with the ATF. ...This work studies the influence of factors like temperature, time, and air exposition on the oxidation of three ATFs and their changes in electrical conductivity. The results showed that the higher content of additive the lower variations of electrical conductivity with the oxidation; the measurements of electrical conductivity are better than FT-IR ones for monitoring oil thermo-oxidative degradation at initial periods; the conventional ATFs could maintain good electrical compatibility in electrified drivelines, although their materials compatibility and copper corrosion protection of electrical components should be also tested.
•Electrical conductivity is a good parameter for monitoring the oxidation of ATFs.•Changes in EC of ATFs are more related to oxidation than to viscosity changes.•The impact of temperature, air flow and time on the ATFs oxidation depend on each oil.•ATFs seems to have electrical compatibility to be used in electrified drivelines.
The importance of chemical composition and microstructure on CO2 corrosion of carbon and low alloy steels has been widely recognized, still contradictory results can be found in the literature. The ...aim of this work is to assess the relationship between microstructure, surface condition and inhibitor efficiency in CO2 corrosion. A C-Mn steel with two different microstructures was tested in a deoxygenated 5% wt. NaCl solution saturated with CO2 at 40 deg C, pH 6. A commercial imidazoline-based inhibitor was added after different pre-corrosion periods. The results obtained showed that pre-corrosion decreases the inhibitor efficiency, but that its impact is microstructure dependent.
PDF
