Cellular Events Under Flow States Pertinent to Heart Valve Function

Heart valve disease (HVD) or a damaged valve can severely compromise the heart\u27s ability to pump efficiently. Balloon valvuloplasty is preferred on neonates with aortic valve stenosis. Even though this procedure decreases the gradient pressure across the aortic valve, restenosis is observed soon after balloon intervention. Tissue engineering heart valves (TEHV), using bone marrow stem cells (BMSCs) and biodegradable scaffolds, have been investigated as an alternative to current non-viable prosthesis. By observing the changes in hemodynamics following balloon aortic valvuloplasty, we could uncover a potential cause for rapid restenosis after balloon intervention. Subsequently, a tissue engineering treatment strategy based on BMSC mechanobiology could be defined. Understanding and identifying the mechanisms by which cytoskeletal changes may lead to cellular differentiation of a valvular phenotype is a first critical step in enhancing the promotion of a robust valvular phenotype from BMSCs

ESTRATEGIAS EDUCATIVAS PARA EL APRENDIZAJE DE COMPETENCIAS PROFESIONALES EN PROGRAMAS ALIMENTARIONUTRIMENTALES EN SALUD PÚBLICA

En el presente estudio, se analiza el proceso educativo para el aprendizaje de competencias profesionales de los alumnos en el campo de la alimentación y nutrición en salud pública de la Licenciatura en Nutrición del Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara, utilizando la estrategia didáctica de integración del trabajo, el servicio y la investigación. Los alumnos aprenden y son evaluados para el desempeño competente para la realización de un diagnóstico situacional como base para la planificación, ejecución y vigilancia epidemiológica de programas alimentario-nutrimentales en espacios sociales del área de salud de Balcones de Arriba en la Zona Metropolitana de Guadalajara. Para organizar el proceso educativo se genera un modelo académico descendente-ascendente en donde los docentes y trabajadores de la institución de salud funcionan como asesores y los alumnos de grados superiores son facilitadores del aprendizaje de alumnos de grados inferiores. Esta experiencia aporta elementos para enriquecer los modelos tutoriales para el aprendizaje de la nutrición en salud pública. Palabras clave: aprendizaje de competencias, evaluación de desempeños, nutrición, salud públicanutrition, public health, redeem evaluation and knowledge

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory

Stem Cell Cytoskeletal Responses to Pulsatile Flow in Heart Valve Tissue Engineering Studies

Heart valve replacement options remain exceedingly limited for pediatric patients because they cannot accommodate somatic growth. To overcome this shortcoming, heart valve tissue engineering using human bone marrow stem cells (HBMSCs) has been considered a potential solution to the treatment of critical congenital valvular defects. The mechanical environments during in vitro culture are key regulators of progenitor cell fate. Here, we report on alterations in HBMSCs, specifically in their actin cytoskeleton and their nucleus under fluid-induced shear stresses of relevance to heart valves. HBMSCs were seeded in microfluidic channels and were exposed to the following conditions: pulsatile shear stress (PSS), steady shear stress (SS), and no flow controls (n = 4/group). Changes to the actin filament structure were monitored and subsequent gene expression was evaluated. A significant increase (p < 0.05) in the number of actin filaments, filament density and angle (between 30° and 84°), and conversely a significant decrease (p < 0.05) in the length of the filaments were observed when the HBMSCs were exposed to PSS for 48 h compared to SS and no flow conditions. No significant differences in nuclear shape were observed among the groups (p > 0.05). Of particular relevance to valvulogenesis, klf2a, a critical gene in valve development, was significantly expressed only by the PSS group (p < 0.05). We conclude that HBMSCs respond to PSS by alterations to their actin filament structure that are distinct from SS and no flow conditions. These changes coupled with the subsequent gene expression findings suggest that at the cellular level, the immediate effect of PSS is to initiate a unique set of quantifiable cytoskeletal events (increased actin filament number, density and angle, but decrease in filament length) in stem cells, which could be useful in the fine-tuning of in vitro protocols in heart valve tissue engineering

Conocimientos generales sobre el Grupo de Alcohólicos Anónimos

El alcoholismo es una enfermedad que constituye un problema a escala mundial y, según estudios realizados por la Organización Mundial de la Salud, los jóvenes representan el grupo más afectado. Para resolver este problema surge el Grupo de Alcohólicos Anónimos, con el objetivo de ayudar a alcanzar la sobriedad. Sobre la base de tales reflexiones se realizó una exhaustiva revisión bibliográfica sobre los principales aspectos del origen y funcionamiento de este grupo, para que toda la comunidad médica de la provincia de Santiago de Cuba conozca este programa, que también se desarrolla en el territori

Quantitative Real Time-Polymerase Chain Reaction.

<p>(a) q(RT-PCR) of HBMSCs derived engineered cartilage integrated to HC-secreted cartilage matrix at a region of 1 cm (proximal) and 4cm (distal) from the interface within the HBMSC construct. In samples both with and without HA, a high expression of Aggrecan, SOX9 and Collagen Type II at both the proximal and distal positions was found, indicative of a healthy articular cartilage phenotype. In addition, in the samples with HA, high gene expression of MMP13, Runx2 Collagen Type X and significant expression of Osteocalcin (p < 0.05) at the proximal location was found. The absence of these bone ECM genes thus preserved the cartilage phenotype when HA was not incorporated in healthy engineered cartilage matrix. (b) q(RT-PCR) of HBMSCs derived engineered cartilage integrated with HCOA-secreted cartilage matrix at a region of 1 cm (proximal) and 4cm (distal) from the interface within the HBMSC portion. In samples with HA, a significantly lower expression of Collagen Type I (p < 0.05) at the proximal location was found, i.e., preservation of the articular cartilage phenotype (while still maintaining robust expression of Aggrecan, SOX9 and Collagen Type II). In the specimens with HA, distal locations deep within the HBMSC-derived engineered tissue did not or negligibly expressed MMP13, Runx2 and Collagen X (p < 0.05). We speculate that the presence of HA at the interface and the subsequent creation of a calcium phosphate-rich transition zone served to potentially further reduce the spread of osteoarthritic conditions to the <i>de novo</i> cartilage formed by the HBMSCs. Note that the expression of MMP13, Runx2 was completely absent in specimens with HA in the deep zone (hence bar not shown), but these findings were nonetheless significantly lower in expression (p < 0.05) compared to the expression of these genes in specimens without HA.</p

Interfacial shear stress.

<p>(a) Tissue engineered cartilage integrated with healthy cartilage mimics with and without the presence of HA. (b) Tissue engineered cartilage integrated with osteoarthritic cartilage mimics with and without presence of HA. The “*” indicates that the difference between the groups was statistically significant (p < 0.05).</p

Energy-Dispersive X-ray Spectroscopy EDS and its map.

<p>(a) Elementary composition of the transition zone using (EDS). A large transition region between engineered cartilage and engineered bone treated with HA was analyzed after 28 days of culture. Elemental Calcium in the order of ∼ 6.41% was found to be present in the transition zone. (b) EDS map of the transition zone with the revelation of both robust presence of phosphorous and calcium, the two primary constituents of HA. The map thereby confirmed HA’s presence within the transition zone.</p

Von Kossa—Alcian Blue histology.

<p>(a) Tissue engineered cartilage derived from HBMSCs integrated with HC-secreted cartilage matrix without HA at Day 1 and at Day 28. (b) Tissue engineered cartilage derived from HBMSCs integrated with HC-secreted cartilage matrix with HA at Day 1 and at Day 28. (c) Tissue engineered cartilage derived from HBMSCs integrated with HCOA-secreted cartilage matrix without HA incorporation at Day 1 and at Day 28. (d) Tissue engineered cartilage derived from HBMSCs integrated with HCOA-secreted cartilage matrix with HA incorporation at Day 1 and at Day 28—Progressive filling of the transition zone with calcium phosphate deposits (indicated by dotted yellow lines) in the group with HA was found to occur. (e) A zoom-in of the transition zone (additional 2.5X that of Fig 3(d)). (f) Even further zoom-in of the transition zone (additional 10X that of Fig 3(d)).</p

Quantitative RT-Polymerase Chain Reaction Primer Sequences.

<p>Quantitative RT-Polymerase Chain Reaction Primer Sequences.</p