Ischemic and non-ischemic patterns of late gadolinium enhancement in heart failure with reduced ejection fraction

Background: Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) may revealmyocardial fibrosis which is associated with adverse clinical outcomes in patients undergoing implantablecardioverter-defibrillator (ICD) placement. At the same time, transmural LGE in the posterolateral wall isrelated to nonresponse to conventional cardiac resynchronization therapy (CRT). Herein, the aim was toassess the presence and determinants of LGE in CMR in heart failure (HF) with reduced ejection fraction.Methods: Sixty-seven patients were included (17.9% female, aged 45 [29–60] years), who underwentLGE-CMR and had left ventricular ejection fraction (LVEF) as determined by echocardiography.Results: In HF patients with LVEF ≤ 35% (n = 29), ischemic and non-ischemic patterns of LGE wereobserved in 51.7% and 34.5% of patients, respectively. In controls (n = 38), these patterns were noted in23.7% and 42.1% of patients, respectively. HF patients with LVEF ≤ 35% and transmural LGE in theposterolateral wall (31.0%) were characterized by older age, coronary artery disease (CAD) and previousmyocardial infarction (MI) (61 ± 6 vs. 49 ± 16 years, p = 0.008, 100% vs. 40%, p = 0.003 and 78%vs. 25%, p = 0.014, respectively). In patients with LVEF ≤ 35%, LGE of any type, diagnosed in 86.2%of patients, was associated with CAD (68% vs. 0%, p = 0.02), while only trends were observed for itsassociation with older age and previous MI (p = 0.08 and p = 0.12, respectively).Conclusions: Among HF patients with LVEF ≤ 35%, clinical factors including older age, CAD, andprevious MI are associated with transmural LGE in the posterolateral wall, while CAD is associated with LGE. This data may have potential implications for planning ICD and CRT placement procedures

The dynamics of liquid slugs forced by a syringe pump

Microfluidic processes for chemical synthesis have become popular in recent years. The small scale of the chemical reactions promise greater control over reaction conditions and more timely creation of products. The small scale of microfluidics poses its own set of problems, however. At the microscale, the dominant fluid forces are viscous resistance and surface tension. The effects of viscosity and scale reduce the Reynolds number and make mixing difficult. Much work has been done to control mixing at the microscale. This problem is concerned with a different microfluidic problem: delivering reactants to the site of reaction. A common setup is to attach syringes full of reactant to a reaction chamber by narrow hydrophobic tubing. Using a stepper motor, a controlled dose of liquid may be injected into the tube. The hydrophobosity causes the dose to curve outward on the sides, becoming a "slug" of reactant with air in front and behind. The syringe at the rear is then switched for one full of air, and air pressure is used to drive the slug to the reaction site. If too much pressure is applied, the slug will arrive with a significant back pressure that will be relieved through bubbling in the reaction site. This causes the formation of a foam and is highly undesirable. We present a simple model based on Boyle’s law for the motion of a slug through a tube. We then extend this model for trains of slugs separated by air bubbles. Last, we consider the case of a flooded reaction site, where the forward air bubble must be pushed through the flooding liquid. In conclusion, we have determined the dynamics of a single slug moving towards an empty reaction chamber giving the final equilibrium position of the slug. A phase-plane analysis then determined a condition on the size of the slug needed to ensure that it comes to rest without oscillating about the equilibrium position. The effect of a flooded reaction chamber was then considered. In this case it is impossible to avoid bubbling due to the design of the device. We found that it is possible, however, to reduce the bubbling by minimising the back pressure behind the slug. Finally, the dynamics of multiple slugs with or without a flooded reaction chamber has been investigated

Endothelial function assessment in atherosclerosis: Comparison of brachial artery flow‑mediated vasodilation and peripheral arterial tonometry

INTRODUCTION Endothelial dysfunction, characterized by the loss of nitric oxide bioavailability, is a key element in the pathogenesis of atherosclerosis and an important prognostic factor in cardiovascular diseases. Therefore, the development of reliable, safe, and noninvasive methods of endothelial function assessment is important for their use in cardiovascular risk stratification. Brachial artery flow‑mediated dilation (FMD) is widely used in research but technical difficulties and problems with calibration between laboratories limit its clinical use. Reactive hyperemia–peripheral artery tonometry (RH‑PAT, EndoPAT) has been developed as a simpler, cheaper, and potentially more reproducible method. OBJECTIVES We aimed to investigate associations between RH‑PAT and FMD in relation to atherosclerotic risk factor profile. PATIENTS AND METHODS The study involved 80 subjects (52 men, 28 women) aged 43.6 ±14.8 years, with moderate‑to‑low cardiovascular risk (mean SCORE, 2.2% ±2%), in whom FMD, RH‑PAT, and intima–media thickness (IMT) were determined. RESULTS The reactive hyperemia index (RHI) measured by RH‑PAT correlated with FMD (r = 0.35, P <0.01). However, no significant correlation was observed between RHI and IMT, SCORE, or the number of classical atherosclerotic risk factors (hypertension, smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated with IMT (r = –0.53, P <0.001), risk factors (r = –0.55, P <0.05), and SCORE (r = –0.4, P <0.05). CONCLUSIONS Despite its technical requirements, FMD is a more sensitive method than RH‑PAT in evaluating the effect of classical atherosclerotic risk factors on vascular endothelial function. Microvasculature response during RH‑PAT needs to be further studied, including the assessment of nonendothelial factors that may affect the measurements, before RH‑PAT becomes the universal tool for the evaluation of the endothelial cells

Molecular evolution of epididymal lipocalin genes localized on mouse chromosome 2

Producción CientíficaWe previously identified two murine secretory proteins, mE-RABP(Lcn5) and mEP17(Lcn8), belonging to the lipocalin family and specifically expressed in the epididymis. The genes are contiguous and localized on mouse chromosome 2. We now show that five other related lipocalin genes, Lcn9, Lcn10, Lcn11, Lcn12, and Lcn13, that evolved by in situ tandem duplication are present on the same locus. Lcn9, Lcn10, Lcn12, and Lcn13 genes, like Lcn5 and Lcn8 genes, are specifically expressed in the mouse epididymis. However, each gene has a distinct spatial expression within the epididymis and different regulation. Analysis of the human genome sequence shows the presence of genes encoding lipocalins with genomic organization, chromosomal arrangement, and orientation similar to that of the corresponding murine genes, indicating that the epididymal cluster is evolutionary conserved. A phylogenetic analysis of the new epididymal proteins reveals their spread position in the lipocalin protein family tree. This suggests the preservation of the regulatory sequences, while protein sequences have greatly diverged, reflecting functional diversity and possibly multifunctionality. In terms of the cluster ancestry, epididymal expression possibly appeared in a PGDS-like lipocalin in amniotes, and the duplications generating the cluster occurred at least in the common ancestor of rodents and primates. The presence and conservation of a cluster of five genes encoding epididymal lipocalins, differently regulated and regionalized in the epididymis, strongly suggests that these proteins may play an important role for male fertility

Human homolog of Drosophila Hairy and enhancer of split 1, Hes1, negatively regulates δ-catenin (CTNND2) expression in cooperation with E2F1 in prostate cancer

<p>Abstract</p> <p>Background</p> <p>Neuronal synaptic junction protein δ-catenin (<it>CTNND2</it>) is often overexpressed in prostatic adenocarcinomas but the mechanisms of its activation are unknown. To address this question, we studied the hypothesis that Hes1, human homolog of <it>Drosophila </it>Hairy and enhancer of split (Hes) 1, is a transcriptional repressor of δ-catenin expression and plays an important role in molecular carcinogenesis.</p> <p>Results</p> <p>We identified that, using a <it>δ-catenin </it>promoter reporter assay, Hes1, but not its inactive mutant, significantly repressed the upregulation of δ-catenin-luciferase activities induced by E2F1. Hes1 binds directly to the E-boxes on <it>δ-catenin </it>promoter and can reduce the expression of δ-catenin in prostate cancer cells. In prostate cancer CWR22-Rv1 and PC3 cell lines, which showed distinct δ-catenin overexpression, E2F1 and Hes1 expression pattern was altered. The suppression of Hes1 expression, either by γ-secretase inhibitors or by siRNA against Hes1, increased δ-catenin expression. γ-Secretase inhibition delayed S/G2-phase transition during cell cycle progression and induced cell shape changes to extend cellular processes in prostate cancer cells. In neuroendocrine prostate cancer mouse model derived allograft NE-10 tumors, δ-catenin showed an increased expression while Hes1 expression was diminished. Furthermore, <it>E2F1 </it>transcription was very high in subgroup of NE-10 tumors in which <it>Hes1 </it>still displayed residual expression, while its expression was only moderately increased in NE-10 tumors where Hes1 expression was completely suppressed.</p> <p>Conclusion</p> <p>These studies support coordinated regulation of δ-catenin expression by both the activating transcription factor E2F1 and repressive transcription factor Hes1 in prostate cancer progression.</p

Molecular cloning and hormonal regulation of a murine epididymal retinoic acid-binding protein messenger ribonucleic acid

A complementary DNA encoding the mouse epididymal secretory protein MEP 10 (mouse epididymal protein 10) was cloned and is now renamed murine epididymal retinoic acid binding protein (mE-RABP). The analysis of the predicted primary amino acid sequence showed that mE-RABP has a 75% identity with rat ESP I (epididymal secretory protein I), another epididymal retinoic acid-binding protein. The homology strongly suggests that mE-RABP is the mouse orthologue of rat ESP I. A computer analysis of the predicted three- dimensional structure confirmed that mE-RABP can accommodate retinoic acid as ligand. In the rat, ESP I messenger RNA (mRNA) is expressed in the efferent ducts and in the entire caput epididymidis. However, in the mouse, the expression of a 950-bp mE-RABP mRNA was detected only in principal cells of the mid/distal caput epididymidis, suggesting that the regulation of region- specific expression is different in rat and mouse. Northern blot analyses showed that mE-RABP gene expression is no longer detected 10 days after castration but progressively rebounds between days 15 and 60. However, mE- RABP protein could not be detected by Western blot 30 days after castration. Androgen replacement, begun 5 days after castration and continued for 4 days restored significant expression of mE-RABP mRNA. Efferent duct ligation for 10 days did not affect gene expression. Taken together, these results indicate that mE-RABP mRNA expression is regulated by androgens but not by testicular factors. The overall similarity in the primary amino acid sequence of mE-RABP with ESP I and other members of the lipocalin superfamily suggests that they are evolutionarily related

Computational and Experimental Investigation of Interfacial Area in Near-Field Diesel Spray Simulation

[EN] The dense spray region in the near-field of diesel fuel injection remains an enigma. This region is difficult to interrogate with light in the visible range and difficult to model due to the rapid interaction between liquid and gas. In particular, modeling strategies that rely on Lagrangian particle tracking of droplets have struggled in this area. To better represent the strong interaction between phases, Eulerian modeling has proven particularly useful. Models built on the concept of surface area density are advantageous where primary and secondary atomization have not yet produced droplets, but rather form more complicated liquid structures. Surface area density, a more general concept than Lagrangian droplets, naturally represents liquid structures, no matter how complex. These surface area density models, however, have not been directly experimentally validated in the past due to the inability of optical methods to elucidate such a quantity. Optical diagnostics traditionally measure near-spherical droplet size far downstream, where the spray is optically thin. Using ultra-small-angle x-ray scattering (USAXS) measurements to measure the surface area and x-ray radiography to measure the density, we have been able to test one of the more speculative parts of Eulerian spray modeling. The modeling and experimental results have been combined to provide insight into near-field spray dynamics.Authors acknowledge that part of this work was partially funded by the Spanish Ministry of Economy and Competitiveness in the frame of the COMEFF (TRA2014-59483-R) project.Pandal, A.; Pastor Enguídanos, JM.; Payri, R.; Kastengren, A.; Duke, DJ.; Matusik, KE.; Giraldo-Valderrama, JS.... (2017). Computational and Experimental Investigation of Interfacial Area in Near-Field Diesel Spray Simulation. SAE International Journal of Fuel and Lubricants. 10(2):1-9. doi:10.4271/2017-01-0859S1910

Energy solutions to one-dimensional singular parabolic problems with BVBV data are viscosity solutions

We study one-dimensional very singular parabolic equations with periodic boundary conditions and initial data in $BV$, which is the energy space. We show existence of solutions in this energy space and then we prove that they are viscosity solutions in the sense of Giga-Giga.Comment: 15 page

Experimental and Computational Investigation of Subcritical Near-Nozzle Spray Structure and Primary Atomization in the Engine Combustion Network Spray D

[EN] In order to improve understanding of the primary atomization process for diesel-like sprays, a collaborative experimental and computational study was focused on the near-nozzle spray structure for the Engine Combustion Network (ECN) Spray D single-hole injector. These results were presented at the 5th Workshop of the ECN in Detroit, Michigan. Application of x-ray diagnostics to the Spray D standard cold condition enabled quantification of distributions of mass, phase interfacial area, and droplet size in the near-nozzle region from 0.1 to 14 mm from the nozzle exit. Using these data, several modeling frameworks, from Lagrangian-Eulerian to Eulerian-Eulerian and from Reynolds-Averaged Navier-Stokes (RANS) to Direct Numerical Simulation (DNS), were assessed in their ability to capture and explain experimentally observed spray details. Due to its computational efficiency, the Lagrangian-Eulerian approach was able to provide spray predictions across a broad range of conditions. In general, this "engineering-level" simulation was able to reproduce the details of the droplet size distribution throughout the spray after calibration of the spray breakup model constants against the experimental data. Complementary to this approach, higher-fidelity modeling techniques were able to provide detailed insight into the experimental trends. For example, interface-capturing multiphase simulations were able to capture the experimentally observed bimodal behavior in the transverse interfacial area distributions in the near-nozzle region. Further analysis of the spray predictions suggests that peaks in the interfacial area distribution may coincide with regions of finely atomized droplets, whereas local minima may coincide with regions of continuous liquid structures. The results from this study highlight the potential of x-ray diagnostics to reveal salient details of the near-nozzle spray structure and to guide improvements to existing primary atomization modeling approaches.Battistoni, M.; Magnotti, GM.; Genzale, CL.; Arienti, M.; Matusik, KE.; Duke, DJ.; Giraldo-Valderrama, JS.... (2018). Experimental and Computational Investigation of Subcritical Near-Nozzle Spray Structure and Primary Atomization in the Engine Combustion Network Spray D. SAE International Journal of Fuel and Lubricants. 11(4):337-352. https://doi.org/10.4271/2018-01-0277S33735211