Experimental investigation of the flow downstream of a dysfunctional bileaflet mechanical aortic valve.

Mechanical heart valve replacement is the preferred alternative in younger patients with severe symptomatic aortic valve disease. However, thrombus and pannus formations are common complications associated with bileaflet mechanical heart valves. This leads to risks of valve leaflet dysfunction, a life-threatening event. In this experimental study, we investigate, using time-resolved planar particle image velocimetry, the flow characteristics in the ascending aorta in the presence of a dysfunctional bileaflet mechanical heart valve. Several configurations of leaflet dysfunction are investigated and the induced flow disturbances in terms of velocity fields, viscous energy dissipation, wall shear stress, and accumulation of viscous shear stresses are evaluated. We also explore the ability of a new set of parameters, solely based on the analysis of the normalized axial velocity profiles in the ascending aorta, to detect bileaflet mechanical heart valve dysfunction and differentiate between the different configurations tested in this study. Our results show that a bileaflet mechanical heart valve dysfunction leads to a complex spectrum of flow disturbances with each flow characteristic evaluated having its own worst case scenario in terms of dysfunction configuration. We also show that the suggested approach based on the analysis of the normalized axial velocity profiles in the ascending aorta has the potential to clearly discriminate not only between normal and dysfunctional bilealfet heart valves but also between the different leaflet dysfunction configurations. This approach could be easily implemented using phase-contrast MRI to follow up patients with bileaflet mechanical heart valves.

A guideline for the distance measurement plans of site-directed spin labels for structural prediction of nucleic acids.

CONTEXT AND RESULTS: Site-directed spin labeling (SDSL) combined with electron paramagnetic resonance spectroscopy methods has been successfully used to predict the structures of nucleic acids. These methods measure the distances between spin labels yielding distance equations that are solved using numerical algorithms to provide one or several structural predictions. In this work, the minimum number of SDSL distance measurements and distance measurement types required to predict a unique nucleic acid structure were investigated. Our results indicate that at least six distance measurements should be obtained given that the distance measurements do not connect one SDSL on one arm with more than three SDSLs on the other arm. Moreover, there may be a preference for 1-to-1 SLs distance measurements rather than 1-to-many SLs as the latter was linked to undefined structures discussed in this study. METHODS: Pairs of double-helical arms of nucleic acid were simulated using the finite element software Pro/ENGINEER (PTC Inc., Boston, MA). In each simulation, a specific SDSL distance measurement plan was adopted and the resulting structure was tested for movability. Immovable structures indicate that this plan will potentially result in a unique structural prediction of the nucleic acid. All the possible plans for SDSL distance measurements were investigated either by direct measurement or by extrapolation.

Red blood cell flow in the cardiovascular system: a fluid dynamics perspective.

The dynamics of red blood cells (RBCs) is one of the major aspects of the cardiovascular system that has been studied intensively in the past few decades. The dynamics of biconcave RBCs are thought to have major influences in cardiovascular diseases, the problems associated with cardiovascular assistive devices, and the determination of blood rheology and properties. This article provides an overview of the works that have been accomplished in the past few decades and aim to study the dynamics of RBCs under different flow conditions. While significant progress has been made in both experimental and numerical studies, a detailed understanding of the behavior of RBCs is still faced with many challenges. Experimentally, the size of RBCs is considered to be a major limitation that allows measurements to be performed under conditions similar to physiological conditions. In numerical computations, researchers still are working to develop a model that can cover the details of the RBC mechanics as it deforms and moves in the bloodstream. Moreover, most of reported computational models have been confined to the behavior of a single RBC in 2-dimensional domains. Advanced models are yet to be developed for accurate description of RBC dynamics under physiological flow conditions in 3-dimensional regimes.

Hemodynamic Performance of Dysfunctional Prosthetic Heart Valve with the Concomitant Presence of Subaortic Stenosis: In Silico Study.

The prosthetic heart valve is vulnerable to dysfunction after surgery, thus a frequent assessment is required. Doppler electrocardiography and its quantitative parameters are commonly used to assess the performance of the prosthetic heart valves and provide detailed information on the interaction between the heart chambers and related prosthetic valves, allowing early detection of complications. However, in the case of the presence of subaortic stenosis, the accuracy of Doppler has not been fully investigated in previous studies and guidelines. Therefore, it is important to evaluate the accuracy of the parameters in such cases to get early detection, and a proper treatment plan for the patient, at the right time. In the current study, a CFD simulation was performed for the blood flow through a Bileaflet Mechanical Heart Valve (BMHV) with concomitant obstruction in the Left Ventricle Outflow Tract (LVOT). The current study explores the impact of the presence of the subaortic on flow patterns. It also investigates the accuracy of (BMHV) evaluation using Doppler parameters, as proposed in the American Society of Echocardiography (ASE) guidelines.

Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.

Accuracy of Doppler-echocardiographic parameters for the detection of aortic bileaflet mechanical prosthetic valve dysfunction.

AIMS: In vitro and in vivo studies were performed to evaluate the diagnostic accuracy of the different Doppler-echocardiographic parameters proposed in the American Society of Echocardiography guidelines to identify dysfunction of bileaflet mechanical valves (BMV) in the aortic position. METHODS AND RESULTS: Two models of BMV (St Jude HP, MCRI On-X) of different sizes (21;23;25;27 mm) were tested in vitro under a wide range of cardiac outputs (3-7 L/min). The motion of one or both leaflets was restricted to induce a mild (25% restriction in total valve orifice area) and moderate-to-severe (50% restriction in total valve area). Doppler-echocardiographic parameters of valve function were also measured in 17 patients with BMV of whom 4 had valve dysfunction confirmed by cinefluoroscopy. The specificity of all the parameters was high (in vitro: 83-100%; in vivo: 69-100%), but the sensitivity was low (range: 0-83% and 25-100%, respectively). A higher cut-off value for the ratio of peak left ventricular outflow tract velocity to peak aortic velocity or Doppler velocity index (DVI) (<0.35 instead of 0.3 or 0.25) improved the sensitivity (>90%) for the detection of moderate-to-severe dysfunction but remained low for mild dysfunction (50%). Furthermore, a difference of normal reference effective orifice area (EOA) minus measured EOA (EOA-D) >1 standard deviation identified mild and moderate-to-severe dysfunction with sensitivity of 61 and 100%, respectively. CONCLUSION: The Doppler-echocardiographic parameters and criteria proposed in the guidelines lack sensitivity for the detection of BMV dysfunction. The utilization of a DVI < 0.35 or an EOA-D > 1 SD improved the sensitivity (>90%) for the detection of moderate-to-severe dysfunction, but the sensitivity remained suboptimal (<65%) for detection of mild dysfunction.