Three-dimensional fluid-structure interaction simulation of the Wheatley aortic valve.

Valvular heart diseases (such as stenosis and regurgitation) are recognized as a rapidly growing cause of global deaths and major contributors to disability. The most effective treatment for these pathologies is the replacement of the natural valve with a prosthetic one. Our work considers an innovative design for prosthetic aortic valves that combines the reliability and durability of artificial valves with the flexibility of tissue valves. It consists of a rigid support and three polymer leaflets which can be cut from an extruded flat sheet, and is referred to hereafter as the Wheatley aortic valve (WAV). As a first step towards the understanding of the mechanical behavior of the WAV, we report here on the implementation of a numerical model built with the ICFD multi-physics solver of the LS-DYNA software. The model is calibrated and validated using data from a basic pulsatile-flow experiment in a water-filled straight tube. Sensitivity to model parameters (contact parameters, mesh size, etc.) and to design parameters (height, material constants) is studied. The numerical data allow us to describe the leaflet motion and the liquid flow in great detail, and to investigate the possible failure modes in cases of unfavorable operational conditions (in particular, if the leaflet height is inadequate). In future work the numerical model developed here will be used to assess the thrombogenic properties of the valve under physiological conditions.

Design and numerical simulation for the development of an expandable paediatric heart valve.

Current paediatric valve replacement options cannot compensate for somatic growth, leading to an obstruction of flow as the child outgrows the prosthesis. This often necessitates an increase in revision surgeries, leading to legacy issues into adulthood. An expandable valve concept was modelled with an inverse relationship between annulus size and height, to retain the leaflet geometry without requiring additional intervention. Parametric design modelling was used to define certain valve parameter aspect ratios in relation to the base radius, Rb, including commissural radius, Rc, valve height, H and coaptation height, x. Fluid-structure simulations were subsequently carried out using the Immersed Boundary method to radially compress down the fully expanded aortic valve whilst subjecting it to diastolic and systolic loading cycles. Leaflet radial displacements were analysed to determine if valve performance is likely to be compromised following compression. Work is ongoing to optimise valvular parameter design for the paediatric patient cohort.

Montreal Communication Evaluation Battery--Portuguese version: age and education effects.

PURPOSE: To verify age and education effects on communication performance of healthy adults in the Montreal Communication Evaluation Battery, Portuguese version (MAC-PT). METHODS: The sample comprised 90 healthy adults from Portugal, European Portuguese speakers, divided into nine groups according to educational level (4-9, 10-13, and > 13 years of formal schooling) and age (19-40, 41-64, and 65-80 years). The influence of age and education was assessed by comparing mean scores between groups, using a two-way analysis of variance followed by Bonferroni post hoc tests (p ≤ 0.05). RESULTS: The results showed that participants' performance was influenced by age in pragmatic-inferential, discursive, and prosodic tasks. Education had the greatest influence on the performance in all processes evaluated by the MAC-PT. CONCLUSION: Age and education seem to influence the communicative performance and should be considered in the assessment of neurological patients.

Bateria Montreal de Avaliação da Comunicação - versão portuguesa: efeito da idade e escolaridade / Montreal Communication Evaluation Battery - Portuguese version: age and education effects

RESUMO Objetivos: Verificar o efeito das variáveis idade e escolaridade no desempenho de adultos saudáveis na Bateria Montreal de Avaliação da Comunicação, versão portuguesa (MAC-PT). Métodos: A amostra foi composta por 90 indivíduos portugueses, falantes do Portugês Europeu, distribuídos em 9 grupos de acordo com a escolaridade (4 a 9; 10 a 13; e mais de 13 anos de ensino formal) e com a idade (19 a 40; 41 a 64; e 65 a 80 anos). Para análise de comparação entre grupos, utilizou-se o testetwo-way ANOVA, com post-hoc Bonferroni (p≤0,05). Resultados: Verificou-se que o desempenho dos indivíduos foi influenciado pela variável idade nas tarefas pragmático-inferencial, discursiva e prosódica. Já a escolaridade influenciou o desempenho em todos os processamentos avaliados pela MAC-PT. Conclusão: As variáveis idade e escolaridade influenciaram o desempenho comunicativo e devem ser consideradas no processo de avaliação de pacientes neurológicos.

ABSTRACT Purpose: To verify age and education effects on communication performance of healthy adults in the Montreal Communication Evaluation Battery, Portuguese version (MAC-PT). Methods: The sample comprised 90 healthy adults from Portugal, European Portuguese speakers, divided into nine groups according to educational level (4-9, 10-13, and >13 years of formal schooling) and age (19-40, 41-64, and 65-80 years). The influence of age and education was assessed by comparing mean scores between groups, using a two-way analysis of variance followed by Bonferroni post hoc tests (p ≤0.05). Results: The results showed that participants' performance was influenced by age in pragmatic-inferential, discursive, and prosodic tasks. Education had the greatest influence on the performance in all processes evaluated by the MAC-PT. Conclusion: Age and education seem to influence the communicative performance and should be considered in the assessment of neurological patients.

Adaptação da Bateria Montreal de Avaliação da Comunicação para o Português Europeu / Adaptation of the Montreal Communication Evaluation Battery to European Portuguese

Objetivo Realizar a adaptação neuropsicolinguística da Bateria Montreal de Avaliação da Comunicação - versão brasileira (Bateria MAC-BR) - à realidade sociocultural portuguesa – Bateria MAC versão Portugal (Bateria MAC-PT).Métodos O processo de adaptação envolveu seis etapas: 1) análise comparativa da Bateria MAC-BR com sua versão original canadense; 2) adaptação e desenvolvimento de novos estímulos por especialistas; 3) análise de juízes não especialistas; 4) análise de juízes especialistas; 5) estudo piloto 1 (n=10); 6) estudo piloto 2 (n=30) e concordância entre avaliadores.Resultados O cumprimento das etapas levou a mudanças importantes na Bateria MAC, que permitiram a adaptação adequada para realidade sociocultural e linguística portuguesa.Conclusão A bateria MAC-PT é uma ferramenta clínica útil para a avaliação da comunicação de pacientes com lesão neurológica.

Purpose To present the adaptation of the Bateria Montreal de Avaliação de Comunicação (Bateria MAC-BR) -to the Portuguese social cultural reality - Bateria MACportuguese version (MAC-PT Battery).Methods The adaptation process involved six steps: 1) comparative analyses ofBateria MAC-BR to its original Canadian version; 2) adaptation and development of new stimuli by specialists; 3) analysis by non-specialist judges, 4) analysis by expert judges; 5) pilot Study 1 (n=10); e 6) pilot Study 2 (n=30) as well as inter-rater agreement.Results The completion of steps permited significant changes in the MAC Battery, which allowed a proper adaptation to the socio-cultural and linguistic Portuguese reality.Conclusion The MAC-PT battery is a useful clinical tool for the communication evaluation of patients with neurological lesion.

GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.

Golgi membranes, from yeast to humans, are uniquely enriched in phosphatidylinositol-4-phosphate (PtdIns(4)P), although the role of this lipid remains poorly understood. Using a proteomic lipid-binding screen, we identify the Golgi protein GOLPH3 (also called GPP34, GMx33, MIDAS, or yeast Vps74p) as a PtdIns(4)P-binding protein that depends on PtdIns(4)P for its Golgi localization. We further show that GOLPH3 binds the unconventional myosin MYO18A, thus connecting the Golgi to F-actin. We demonstrate that this linkage is necessary for normal Golgi trafficking and morphology. The evidence suggests that GOLPH3 binds to PtdIns(4)P-rich trans-Golgi membranes and MYO18A conveying a tensile force required for efficient tubule and vesicle formation. Consequently, this tensile force stretches the Golgi into the extended ribbon observed by fluorescence microscopy and the familiar flattened form observed by electron microscopy.

PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis.

Phosphoinositides play important roles in regulating the cytoskeleton and vesicle trafficking, potentially important processes at the cleavage furrow. However, it remains unclear which, if any, of the phosphoinositides play a role during cytokinesis. A systematic analysis to determine if any of the phosphoinositides might be present or of functional importance at the cleavage furrow has not been published. Several studies hint at a possible role for one or more phosphoinositides at the cleavage furrow. The best of these are genetic data identifying mutations in phosphoinositide-modifying enzymes (a PtdIns(4)P-5-kinase in S. pombe and a PI-4-kinase in D. melanogaster) that interfere with cytokinesis. The genetic nature of these experiments leaves questions as to how direct may be their contribution to cytokinesis. Here we show that a single phosphoinositide, PtdIns(4,5)P2, specifically accumulates at the furrow. Interference with PtdIns(4,5)P2 interferes with adhesion of the plasma membrane to the contractile ring at the furrow. Finally, four distinct interventions to specifically interfere with PtdIns(4,5)P2 each impair cytokinesis. We conclude that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal cytokinesis at least in part because of a role in adhesion between the contractile ring and the plasma membrane.

A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast.

The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels comparable to those in mammalian cells, indicating that a pathway exists for synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN, suppresses PI(3,4,5)P3 levels. By examining various mutants, we show that synthesis of PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3-kinase, vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but does not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These studies suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class III phosphoinositide 3-kinase evolved before the appearance of class I phosphoinositide 3-kinases.