Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation

Mitral regurgitation is a common mitral valve dysfunction which may lead to heart failure. Because of the rapid aging of the population, conventional surgical repair and replacement of the pathological valve are often unsuitable for about half of symptomatic patients, who are judged high-risk. Transcatheter valve implantation could represent an effective solution. However, currently available aortic valve devices are inapt for the mitral position. This paper presents the design, development and hydrodynamic assessment of a novel bi-leaflet mitral valve suitable for transcatheter implantation. The device consists of two leaflets and a sealing component made from bovine pericardium, supported by a self-expanding wireframe made from superelastic NiTi alloy. A parametric design procedure based on numerical simulations was implemented to identify design parameters providing acceptable stress levels and maximum coaptation area for the leaflets. The wireframe was designed to host the leaflets and was optimised numerically to minimise the stresses for crimping in an 8 mm sheath for percutaneous delivery. Prototypes were built and their hydrodynamic performances were tested on a cardiac pulse duplicator, in compliance with the ISO5840-3:2013 standard. The numerical results and hydrodynamic tests show the feasibility of the device to be adopted as a transcatheter valve implant for treating mitral regurgitation

Toxic effects of phenothiazines on the eye

Publications about the retinotoxic action of phenothiazine derivatives led the author to undertake an ophthalmological investigation in two psychiatric hospitals in The Netherlands. The pharmacological actions of phenothiazine preparations are listed and a survey of the phenothiazine derivatives which are at present in use is given. Some retinotoxic substances are discussed and a survey is given of the literature on the ocular complications of phenothiazine therapy. The eyes of 561 patients were examined. of whom 541 are included in this study. 343 of these patients(63.4 %) were found to have retinopathy. The correlation between the retinopathy and the total dose of phenothiazine preparations taken. and between the retinopathy and the duration of treatment. was highly significant. The correlation between the retinopathy and the average daily dose taken was significant. The retinopathy was associated with a reduced standing potential of the eye. as determined by electro-oculography. It was possibly responsible for diminished visual acuity in some cases, and for an abnormally large proportion of protans in the group of patients with colour defects. It was not possible to ascribe a more severe retinotoxic action to one or more specific phenothiazine derivatives than to others. In the author's opinion regular examination of the eyes of patients who are being treated with phenothiazine preparations in high dosage and for for a long period of time is indicated

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain

Deformable templates for tracking and analysis of intravascular ultrasound sequences

Deformable Template models are first applied to track the inner wall of coronary arteries in intravascular ultrasound sequences, mainly in the assistance to angioplasty surgery. A circular template is used for initializing an elliptical deformable model to track wall deformation when inflating a balloon placed at the tip of the catheter. We define a new energy function for driving the behavior of the template and we test its robustness both in real and synthetic images. Finally we introduce a framework for learning and recognizing spatio-temporal geometric constraints based on Principal Component Analysis (eigenconstraints)