Long-term follow-up of asymptomatic or mildly symptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular function

OBJECTIVES: The timing for mitral valve surgery in asymptomatic patients with severe mitral regurgitation and preserved left ventricular function remains controversial. We analyzed the immediate and long-term outcomes of these patients after surgery. METHODS: From January 1992 to December 2012, 382 consecutive patients with severe chronic degenerative mitral regurgitation, with no or mild symptoms, and preserved left ventricular function (ejection fraction ≥ 60%) were submitted to surgery and followed for up to 22 years (3209 patient-years). Patients with associated surgeries, other than tricuspid valve repair, were excluded. Cox proportional-hazard survival analysis was performed to determine predictors of late mortality and mitral reoperation. Subgroup analysis involved patients with atrial fibrillation or pulmonary hypertension. RESULTS: Mitral valvuloplasty was performed in 98.2% of cases. Thirty-day mortality was 0.8%. Overall survival at 5, 10, and 20 years was 96.3% ± 1.0%, 89.7% ± 2.0%, and 72.4% ± 5.8%, respectively, and similar to the expected age- and gender-adjusted general population. Patients with atrial fibrillation/pulmonary hypertension had a 2-fold risk of late mortality compared with the remaining patients (hazard ratio, 2.54; 95% confidence interval, 1.17-4.80; P = .018). Benefit was age-dependent only in younger patients (<65 years; P = .016). Patients with atrial fibrillation/pulmonary hypertension (hazard ratio, 4.20, confidence interval, 1.10-11.20; P = .037) and patients with chordal shortening were at increased risk for reoperation, whereas patients with P2 prolapse (hazard ratio, 0.06; confidence interval, 0.008-0.51; P = .037) and patients with myxomatous valves (hazard ratio, 0.072; confidence interval, 0.008-0.624; P = .017) were at decreased risk. CONCLUSIONS: Mitral valve repair can be achieved in the majority of patients with low mortality (<1%) and excellent long-term survival. Patients with atrial fibrillation/pulmonary hypertension had compromised long-term survival, particularly younger patients (aged <65 years), and are at increased risk of mitral reoperation.info:eu-repo/semantics/publishedVersio

TRANSPORT LENGTH, QUANTUM EFFICIENCY, AND TRAP DENSITY-MEASUREMENT IN BI12SIO20

66124725

PHASE-SHIFT MEASUREMENT IN PHOTOREFRACTIVE HOLOGRAPHIC RECORDING

661474

Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using singlemolecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function

Feasibility of Noninvasive Positive Pressure Ventilation in the Treatment of Oxygen-Dependent COVID-19 Patients in Peru

Intensive care is expensive, and availability is limited. Low- and middle-income countries in particular have struggled to cope with the large influx of critically ill patients during the COVID-19 pandemic. Noninvasive respiratory support devices delivering continuous positive airways pressure (CPAP) require less resource and staff expertise compared with invasive mechanical ventilators and can be routinely used outside of intensive care units. This study assessed the use of the UCL-Ventura Wayrachi CPAP device in hospitalized patients with COVID-19 in Peru. A secondary analysis of data collected for a feasibility study commissioned by the Peruvian Ministry of Health was conducted. Data were collected from three hospitals, including patient demographics, clinical data, and outcomes. Forty-five patients were enrolled from July 16 to September 1, 2020. Eight patients (18%) were intolerant of the CPAP mask. Of the remainder, 18 (48.7%) improved and were discharged from hospital after 6 days. Eight (21.6%) died while on CPAP and 11 (29.7%) were eventually intubated, of whom two died. In total, 27 (60%) survived to hospital discharge. Participating physicians noted the device was easy to use and provided patient benefit, though voiced concerns about the strain on hospital oxygen supplies. In conclusion, the UCL Ventura Wayrachi CPAP device proved feasible in COVID-19 patients in Peru, and offered a bridging therapy for patients who required a ventilator when none were available

Avoiding hologram bending in photorefractive crystals

coupled-wave theory predicts the bending of recorded hologram phase planes in most photorefractive crystals. Bent holograms occur in LiNbO3 and other photovoltaic crystals that are particularly interesting as holographic storage media and result in a reduced overall diffraction efficiency. We show that hologram bending in LiNbO3 can be avoided or at least sensibly reduced by use of an actively stabilized recording technique. (C) 1996 Optical Society of America21215215

A model for selection of eyespots on butterfly wings

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel