ATTITUDES AND PRACTICES OF GENETIC COUNSELORS IN PROVIDING PREDICTIVE TESTING TO MINORS AT RISK FOR LI-FRAUMENI SYNDROME

Li- Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome caused by mutations in the TP53 gene that predisposes individuals to a wide variety of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, and adrenocortical carcinomas. Individuals found to carry germline mutations in TP53 have a 90% lifetime cancer risk, with a 20% chance to develop cancer under the age of 20. Despite the significant risk of childhood cancer, predictive testing for unaffected minors at risk for LFS historically has not been recommended, largely due to the lack of available and effective screening for the types of cancers involved. A recently developed screening protocol suggests an advantage to identifying and screening children at risk for LFS and we therefore hypothesized that this alongside with the availability of new screening modalities may substantiate a shift in recommendations for predictive genetic testing in minors at risk for LFS. We aimed to describe current screening recommendations that genetic counselors provide to this population as well as explore factors that may have influenced genetic counselors attitude and practice in regards to this issue. An online survey was emailed to members of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). Of an estimated 1000 eligible participants, 172 completed surveys that were analyzed. Genetic counselors in this study were more likely to support predictive genetic testing for this population as the minor aged (p

(Table 1) List of studied samples with vestimentiferan tubes

Vestimentiferan tube worms are prominent members of modern methane seep communities and are totally reliant as adults on symbiotic sulphide-oxidizing bacteria for their nutrition. The sulphide is produced in the sediment by a biochemical reaction called the anaerobic oxidation of methane (AOM). A well-studied species from the Gulf of Mexico shows that seep vestimentiferans 'mine' sulphide from the sediment using root-like, thin walled, permeable posterior tube extensions, which can also be used to pump sulphate and possibly hydrogen ions from the soft tissue back into the sediment to increase the local rate of AOM. The 'root-balls' of exhumed seep vestimentiferans are intimately associated with carbonate nodules, which are a result of AOM. We have studied vestimentiferan specimens and associated carbonates from seeps at the Kouilou pockmark field on the Congo deep-sea fan and find that some of the posterior 'root' tubes of living specimens are enclosed with carbonate indurated sediment and other, empty examples are partially or completely replaced by the carbonate mineral aragonite. This replacement occurs from the outside of the tube wall inwards and leaves fine-scale relict textures of the original organic tube wall. The process of mineralization is unknown, but is likely a result of post-mortem microbial decay of the tube wall proteins by microorganisms or the precipitation from locally high flux of AOM derived carbonate ions. The aragonite-replaced tubes from the Kouilou pockmarks show similar features to carbonate tubes in ancient seep deposits and make it more likely that many of these fossil tubes are those of vestimentiferans. These observations have implications for the supposed origination of this group, based on molecular divergence estimates.

Interactive effects of salinity and elevated CO2 levels on juvenile eastern oysters, Crassostrea virginica

Rising levels of atmospheric CO2 lead to acidification of the ocean and alter seawater carbonate chemistry, which can negatively impact calcifying organisms, including mollusks. In estuaries, exposure to elevated CO2 levels often co-occurs with other stressors, such as reduced salinity, which enhances the acidification trend, affects ion and acid-base regulation of estuarine calcifiers and modifies their response to ocean acidification. We studied the interactive effects of salinity and partial pressure of CO2 (PCO2) on biomineralization and energy homeostasis in juveniles of the eastern oyster, Crassostrea virginica, a common estuarine bivalve. Juveniles were exposed for 11 weeks to one of two environmentally relevant salinities (30 or 15 PSU) either at current atmospheric PCO2 (400 µatm, normocapnia) or PCO2 projected by moderate IPCC scenarios for the year 2100 (700-800 µatm, hypercapnia). Exposure of the juvenile oysters to elevated PCO2 and/or low salinity led to a significant increase in mortality, reduction of tissue energy stores (glycogen and lipid) and negative soft tissue growth, indicating energy deficiency. Interestingly, tissue ATP levels were not affected by exposure to changing salinity and PCO2, suggesting that juvenile oysters maintain their cellular energy status at the expense of lipid and glycogen stores. At the same time, no compensatory upregulation of carbonic anhydrase activity was found under the conditions of low salinity and high PCO2. Metabolic profiling using magnetic resonance spectroscopy revealed altered metabolite status following low salinity exposure; specifically, acetate levels were lower in hypercapnic than in normocapnic individuals at low salinity. Combined exposure to hypercapnia and low salinity negatively affected mechanical properties of shells of the juveniles, resulting in reduced hardness and fracture resistance. Thus, our data suggest that the combined effects of elevated PCO2 and fluctuating salinity may jeopardize the survival of eastern oysters because of weakening of their shells and increased energy consumption.

Computerized Three-Dimmensional Craniofacial Reconstruction from Skulls Based on Landmarks.

Human identification from a skull is a critical process in legal and forensic medicine, specially when no other means are available. Traditional clay-based methods attempt to generate the human face, in order to identify the corresponding person. However, these reconstructions lack of objectivity and consistence, since they depend on the practitioner. Current computerized techniques are based on facial models, which introduce undesired facial features when the final reconstruction is built. This paper presents an objective 3D craniofacial reconstruction technique, implemented in a graphic application, without using any facial template. The only information required by the software tool is the 3D image of the target skull and three parameters: age, gender and Body Mass Index (BMI) of the individual. Complexity is minimized, since the application database only consists of the anthropological information provided by soft tissue depth values in a set of points of the skull.

Multimodal non-rigid image registration methods for therapy and surgery planning

La planificación pre-operatoria se ha convertido en una tarea esencial en cirugías y terapias de marcada complejidad, especialmente aquellas relacionadas con órgano blando. Un ejemplo donde la planificación preoperatoria tiene gran interés es la cirugía hepática. Dicha planificación comprende la detección e identificación precisa de las lesiones individuales y vasos así como la correcta segmentación y estimación volumétrica del hígado funcional. Este proceso es muy importante porque determina tanto si el paciente es un candidato adecuado para terapia quirúrgica como la definición del abordaje a seguir en el procedimiento. La radioterapia de órgano blando es un segundo ejemplo donde la planificación se requiere tanto para la radioterapia externa convencional como para la radioterapia intraoperatoria. La planificación comprende la segmentación de tumor y órganos vulnerables y la estimación de la dosimetría. La segmentación de hígado funcional y la estimación volumétrica para planificación de la cirugía se estiman habitualmente a partir de imágenes de tomografía computarizada (TC). De igual modo, en la planificación de radioterapia, los objetivos de la radiación se delinean normalmente sobre TC. Sin embargo, los avances en las tecnologías de imagen de resonancia magnética (RM) están ofreciendo progresivamente ventajas adicionales. Por ejemplo, se ha visto que el ratio de detección de metástasis hepáticas es significativamente superior en RM con contraste Gd–EOB–DTPA que en TC. Por tanto, recientes estudios han destacado la importancia de combinar la información de TC y RM para conseguir el mayor nivel posible de precisión en radioterapia y para facilitar una descripción precisa de las lesiones del hígado. Con el objetivo de mejorar la planificación preoperatoria en ambos escenarios se precisa claramente de un algoritmo de registro no rígido de imagen. Sin embargo, la gran mayoría de sistemas comerciales solo proporcionan métodos de registro rígido. Las medidas de intensidad de voxel han demostrado ser criterios de similitud de imágenes robustos, y, entre ellas, la Información Mutua (IM) es siempre la primera elegida en registros multimodales. Sin embargo, uno de los principales problemas de la IM es la ausencia de información espacial y la asunción de que las relaciones estadísticas entre las imágenes son homogéneas a lo largo de su domino completo. La hipótesis de esta tesis es que la incorporación de información espacial de órganos al proceso de registro puede mejorar la robustez y calidad del mismo, beneficiándose de la disponibilidad de las segmentaciones clínicas. En este trabajo, se propone y valida un esquema de registro multimodal no rígido 3D usando una nueva métrica llamada Información Mutua Centrada en el Órgano (Organ-Focused Mutual Information metric (OF-MI)) y se compara con la formulación clásica de la Información Mutua. Esto permite mejorar los resultados del registro en áreas problemáticas incorporando información regional al criterio de similitud, beneficiándose de la disponibilidad real de segmentaciones en protocolos estándares clínicos, y permitiendo que la dependencia estadística entre las dos modalidades de imagen difiera entre órganos o regiones. El método propuesto se ha aplicado al registro de TC y RM con contraste Gd–EOB–DTPA así como al registro de imágenes de TC y MR para planificación de radioterapia intraoperatoria rectal. Adicionalmente, se ha desarrollado un algoritmo de apoyo de segmentación 3D basado en Level-Sets para la incorporación de la información de órgano en el registro. El algoritmo de segmentación se ha diseñado específicamente para la estimación volumétrica de hígado sano funcional y ha demostrado un buen funcionamiento en un conjunto de imágenes de TC abdominales. Los resultados muestran una mejora estadísticamente significativa de OF-MI comparada con la Información Mutua clásica en las medidas de calidad de los registros; tanto con datos simulados (p<0.001) como con datos reales en registro hepático de TC y RM con contraste Gd– EOB–DTPA y en registro para planificación de radioterapia rectal usando OF-MI multi-órgano (p<0.05). Adicionalmente, OF-MI presenta resultados más estables con menor dispersión que la Información Mutua y un comportamiento más robusto con respecto a cambios en la relación señal-ruido y a la variación de parámetros. La métrica OF-MI propuesta en esta tesis presenta siempre igual o mayor precisión que la clásica Información Mutua y consecuentemente puede ser una muy buena alternativa en aplicaciones donde la robustez del método y la facilidad en la elección de parámetros sean particularmente importantes. Abstract Pre-operative planning has become an essential task in complex surgeries and therapies, especially for those affecting soft tissue. One example where soft tissue preoperative planning is of high interest is liver surgery. It involves the accurate detection and identification of individual liver lesions and vessels as well as the proper functional liver segmentation and volume estimation. This process is very important because it determines whether the patient is a suitable candidate for surgical therapy and the type of procedure. Soft tissue radiation therapy is a second example where planning is required for both conventional external and intraoperative radiotherapy. It involves the segmentation of the tumor target and vulnerable organs and the estimation of the planned dose. Functional liver segmentations and volume estimations for surgery planning are commonly estimated from computed tomography (CT) images. Similarly, in radiation therapy planning, targets to be irradiated and healthy and vulnerable tissues to be protected from irradiation are commonly delineated on CT scans. However, developments in magnetic resonance imaging (MRI) technology are progressively offering advantages. For instance, the hepatic metastasis detection rate has been found to be significantly higher in Gd–EOB–DTPAenhanced MRI than in CT. Therefore, recent studies highlight the importance of combining the information from CT and MRI to achieve the highest level of accuracy in radiotherapy and to facilitate accurate liver lesion description. In order to improve those two soft tissue pre operative planning scenarios, an accurate nonrigid image registration algorithm is clearly required. However, the vast majority of commercial systems only provide rigid registration. Voxel intensity measures have been shown to be robust measures of image similarity, and among them, Mutual Information (MI) is always the first candidate in multimodal registrations. However, one of the main drawbacks of Mutual Information is the absence of spatial information and the assumption that statistical relationships between images are the same over the whole domain of the image. The hypothesis of the present thesis is that incorporating spatial organ information into the registration process may improve the registration robustness and quality, taking advantage of the clinical segmentations availability. In this work, a multimodal nonrigid 3D registration framework using a new Organ- Focused Mutual Information metric (OF-MI) is proposed, validated and compared to the classical formulation of the Mutual Information (MI). It allows improving registration results in problematic areas by adding regional information into the similitude criterion taking advantage of actual segmentations availability in standard clinical protocols and allowing the statistical dependence between the two modalities differ among organs or regions. The proposed method is applied to CT and T1 weighted delayed Gd–EOB–DTPA-enhanced MRI registration as well as to register CT and MRI images in rectal intraoperative radiotherapy planning. Additionally, a 3D support segmentation algorithm based on Level-Sets has been developed for the incorporation of the organ information into the registration. The segmentation algorithm has been specifically designed for the healthy and functional liver volume estimation demonstrating good performance in a set of abdominal CT studies. Results show a statistical significant improvement of registration quality measures with OF-MI compared to MI with both simulated data (p<0.001) and real data in liver applications registering CT and Gd–EOB–DTPA-enhanced MRI and in registration for rectal radiotherapy planning using multi-organ OF-MI (p<0.05). Additionally, OF-MI presents more stable results with smaller dispersion than MI and a more robust behavior with respect to SNR changes and parameters variation. The proposed OF-MI always presents equal or better accuracy than the classical MI and consequently can be a very convenient alternative within applications where the robustness of the method and the facility to choose the parameters are particularly important.

Regional and seasonal patterns of litterfall in tropical South America

The production of aboveground soft tissue represents an important share of total net primary production in tropical rain forests. Here we draw from a large number of published and unpublished datasets (n = 81 sites) to assess the determinants of litterfall variation across South American tropical forests. We show that across old-growth tropical rainforests, litterfall averages 8.61±1.91Mgha?1 yr?1 (mean±standard deviation, in dry mass units). Secondary forests have a lower annual litterfall than old-growth tropical forests with a mean of 8.01±3.41Mgha?1 yr?1. Annual litterfall shows no significant variation with total annual rainfall, either globally or within forest types. It does not vary consistently with soil type, except in the poorest soils (white sand soils), where litterfall is significantly lower than in other soil types (5.42±1.91Mgha?1 yr?1). We also study the determinants of litterfall seasonality, and find that it does not depend on annual rainfall or on soil type. However, litterfall seasonality is significantly positively correlated with rainfall seasonality. Finally, we assess how much carbon is stored in reproductive organs relative to photosynthetic organs. Mean leaf fall is 5.74±1.83Mgha?1 yr?1 (71% of total litterfall). Mean allocation into reproductive organs is 0.69±0.40Mgha?1 yr?1 (9% of total litterfall). The investment into reproductive organs divided by leaf litterfall increases with soil fertility, suggesting that on poor soils, the allocation to photosynthetic organs is prioritized over that to reproduction. Finally, we discuss the ecological and biogeochemical implications of these results.

Quantitative evaluation of patient-specific conforming hexahedral meshes of abdominal aortic aneurysms and intraluminal thrombus generated from MRI

A novel method for generating patient-specific high quality conforming hexahedral meshes is presented. The meshes are directly obtained from the segmentation of patient magnetic resonance (MR) images of abdominal aortic aneu-rysms (AAA). The MRI permits distinguishing between struc-tures of interest in soft tissue. Being so, the contours of the lumen, the aortic wall and the intraluminal thrombus (ILT) are available and thus the meshes represent the actual anato-my of the patient?s aneurysm, including the layered morpholo-gies of these structures. Most AAAs are located in the lower part of the aorta and the upper section of the iliac arteries, where the inherent tortuosity of the anatomy and the presence of the ILT makes the generation of high-quality elements at the bifurcation is a challenging task. In this work we propose a novel approach for building quadrilateral meshes for each surface of the sectioned geometry, and generating conforming hexahedral meshes by combining the quadrilateral meshes. Conforming hexahedral meshes are created for the wall and the ILT. The resulting elements are evaluated on four patients? datasets using the Scaled Jacobian metric. Hexahedral meshes of 25,000 elements with 94.8% of elements well-suited for FE analysis are generated.

Generación de modelos físicos personalizados y segmentación de la pared arterial y el trombo intraluminal en imágenes de aneurismas aórticos abdominales

Esta tesis doctoral está encuadrada dentro del marco general de la ingeniería biomédica aplicada al tratamiento de las enfermedades cardiovasculares, enfermedades que provocan alrededor de 1.9 millones (40%) de muertes al año en la Unión Europea. En este contexto surge el proyecto europeo SCATh-Smart Catheterization, cuyo objetivo principal es mejorar los procedimientos de cateterismo aórtico introduciendo nuevas tecnologías de planificación y navegación quirúrgica y minimizando el uso de fluoroscopía. En particular, esta tesis aborda el modelado y diagnóstico de aneurismas aórticos abdominales (AAA) y del trombo intraluminal (TIL), allí donde esté presente, así como la segmentación de estas estructuras en imágenes preoperatorias de RM. Los modelos físicos específicos del paciente, construidos a partir de imágenes médicas preoperatorias, tienen múltiples usos, que van desde la evaluación preoperatoria de estructuras anatómicas a la planificación quirúrgica para el guiado de catéteres. En el diagnóstico y tratamiento de AAA, los modelos físicos son útiles a la hora de evaluar diversas variables biomecánicas y fisiológicas de las estructuras vasculares. Existen múltiples técnicas que requieren de la generación de modelos físicos que representen la anatomía vascular. Una de las principales aplicaciones de los modelos físicos es el análisis de elementos finitos (FE). Las simulaciones de FE para AAA pueden ser específicas para el paciente y permiten modelar estados de estrés complejos, incluyendo los efectos provocados por el TIL. La aplicación de métodos numéricos de análisis tiene como requisito previo la generación de una malla computacional que representa la geometría de interés mediante un conjunto de elementos poliédricos, siendo los hexaédricos los que presentan mejores resultados. En las estructuras vasculares, generar mallas hexaédricas es un proceso especialmente exigente debido a la compleja anatomía 3D ramificada. La mayoría de los AAA se encuentran situados en la bifurcación de la arteria aorta en las arterias iliacas y es necesario modelar de manera fiel dicha bifurcación. En el caso de que la sangre se estanque en el aneurisma provocando un TIL, éste forma una estructura adyacente a la pared aórtica. De este modo, el contorno externo del TIL es el mismo que el contorno interno de la pared, por lo que las mallas resultantes deben reflejar esta particularidad, lo que se denomina como "mallas conformadas". El fin último de este trabajo es modelar las estructuras vasculares de modo que proporcionen nuevas herramientas para un mejor diagnóstico clínico, facilitando medidas de riesgo de rotura de la arteria, presión sistólica o diastólica, etc. Por tanto, el primer objetivo de esta tesis es diseñar un método novedoso y robusto para generar mallas hexaédricas tanto de la pared aórtica como del trombo. Para la identificación de estas estructuras se utilizan imágenes de resonancia magnética (RM). Deben mantenerse sus propiedades de adyacencia utilizando elementos de alta calidad, prestando especial atención al modelado de la bifurcación y a que sean adecuadas para el análisis de FE. El método tiene en cuenta la evolución de la línea central del vaso en el espacio tridimensional y genera la malla directamente a partir de las imágenes segmentadas, sin necesidad de reconstruir superficies triangulares. Con el fin de reducir la intervención del usuario en el proceso de generación de las mallas, es también objetivo de esta tesis desarrollar un método de segmentación semiautomática de las distintas estructuras de interés. Las principales contribuciones de esta tesis doctoral son: 1. El diseño, implementación y evaluación de un algoritmo de generación de mallas hexaédricas conformadas de la pared y el TIL a partir de los contornos segmentados en imágenes de RM. Se ha llevado a cabo una evaluación de calidad que determine su aplicabilidad a métodos de FE. Los resultados demuestran que el algoritmo desarrollado genera mallas conformadas de alta calidad incluso en la región de la bifurcación, que son adecuadas para su uso en métodos de análisis de FE. 2. El diseño, implementación y evaluación de un método de segmentación automático de las estructuras de interés. La luz arterial se segmenta de manera semiautomática utilizando un software disponible a partir de imágenes de RM con contraste. Los resultados de este proceso sirven de inicialización para la segmentación automática de las caras interna y externa de la pared aórtica utilizando métodos basado en modelos de textura y forma a partir de imágenes de RM sin contraste. Los resultados demuestran que el algoritmo desarrollado proporciona segmentaciones fieles de las distintas estructuras de interés. En conclusión, el trabajo realizado en esta tesis doctoral corrobora las hipótesis de investigación postuladas, y pretende servir como aportación para futuros avances en la generación de modelos físicos de geometrías biológicas. ABSTRACT The frame of this PhD Thesis is the biomedical engineering applied to the treatment of cardiovascular diseases, which cause around 1.9 million deaths per year in the European Union and suppose about 40% of deaths per year. In this context appears the European project SCATh-Smart Catheterization. The main objective of this project is creating a platform which improves the navigation of catheters in aortic catheterization minimizing the use of fluoroscopy. In the framework of this project, the specific field of this PhD Thesis is the diagnosis and modeling of abdominal aortic aneurysm (AAAs) and the intraluminal thrombus (ILT) whenever it is present. Patient-specific physical models built from preoperative imaging are becoming increasingly important in the area of minimally invasive surgery. These models can be employed for different purposes, such as the preoperatory evaluation of anatomic structures or the surgical planning for catheter guidance. In the specific case of AAA diagnosis and treatment, physical models are especially useful for evaluating pressures over vascular structures. There are multiple techniques that require the generation of physical models which represent the target anatomy. Finite element (FE) analysis is one the principal applications for physical models. FE simulations for AAA may be patient-specific and allow modeling biomechanical and physiological variables including those produced by ILT, and also the segmentation of those anatomical structures in preoperative MR images. Applying numeric methods requires the generation of a proper computational mesh. These meshes represent the patient anatomy using a set of polyhedral elements, with hexahedral elements providing better results. In the specific case of vascular structures, generating hexahedral meshes is a challenging task due to the complex 3D branching anatomy. Each patient’s aneurysm is unique, characterized by its location and shape, and must be accurately represented for subsequent analyses to be meaningful. Most AAAs are located in the region where the aorta bifurcates into the iliac arteries and it is necessary to model this bifurcation precisely and reliably. If blood stagnates in the aneurysm and forms an ILT, it exists as a conforming structure with the aortic wall, i.e. the ILT’s outer contour is the same as the wall’s inner contour. Therefore, resulting meshes must also be conforming. The main objective of this PhD Thesis is designing a novel and robust method for generating conforming hexahedral meshes for the aortic wall and the thrombus. These meshes are built using largely high-quality elements, especially at the bifurcation, that are suitable for FE analysis of tissue stresses. The method accounts for the evolution of the vessel’s centerline which may develop outside a single plane, and generates the mesh directly from segmented images without the requirement to reconstruct triangular surfaces. In order to reduce the user intervention in the mesh generation process is also a goal of this PhD. Thesis to develop a semiautomatic segmentation method for the structures of interest. The segmentation is performed from magnetic resonance image (MRI) sequences that have tuned to provide high contrast for the arterial tissue against the surrounding soft tissue, so that we determine the required information reliably. The main contributions of this PhD Thesis are: 1. The design, implementation and evaluation of an algorithm for generating hexahedral conforming meshes of the arterial wall and the ILT from the segmented contours. A quality inspection has been applied to the meshes in order to determine their suitability for FE methods. Results show that the developed algorithm generates high quality conforming hexahedral meshes even at the bifurcation region. Thus, these meshes are suitable for FE analysis. 2. The design, implementation and evaluation of a semiautomatic segmentation method for the structures of interest. The lumen is segmented in a semiautomatic way from contrast filled MRI using an available software. The results obtained from this process are used to initialize the automatic segmentation of the internal and external faces of the aortic wall. These segmentations are performed by methods based on texture and shape models from MRI with no contrast. The results show that the algorithm provides faithful segmentations of the structures of interest requiring minimal user intervention. In conclusion, the work undertaken in this PhD. Thesis verifies the investigation hypotheses. It intends to serve as basis for future physical model generation of proper biological anatomies used by numerical methods.

High-quality conforming hexahedral meshes of patient-specific abdominal aortic aneurysms including their intraluminal thrombi

In order to perform finite element (FE) analyses of patient-specific abdominal aortic aneurysms, geometries derived from medical images must be meshed with suitable elements. We propose a semi-automatic method for generating conforming hexahedral meshes directly from contours segmented from medical images. Magnetic resonance images are generated using a protocol developed to give the abdominal aorta high contrast against the surrounding soft tissue. These data allow us to distinguish between the different structures of interest. We build novel quadrilateral meshes for each surface of the sectioned geometry and generate conforming hexahedral meshes by combining the quadrilateral meshes. The three-layered morphology of both the arterial wall and thrombus is incorporated using parameters determined from experiments. We demonstrate the quality of our patient-specific meshes using the element Scaled Jacobian. The method efficiently generates high-quality elements suitable for FE analysis, even in the bifurcation region of the aorta into the iliac arteries. For example, hexahedral meshes of up to 125,000 elements are generated in less than 130 s, with 94.8 % of elements well suited for FE analysis. We provide novel input for simulations by independently meshing both the arterial wall and intraluminal thrombus of the aneurysm, and their respective layered morphologies.

Low-Intensity Pulsed Ultrasound Improves the Functional Properties of Cardiac Mesoangioblasts

Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a noninvasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5´-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of β1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy

AVALIAÇÃO CEFALOMÉTRICA DO TECIDO MOLE EM JOVENS COM OCLUSÃO NORMAL: APLICAÇÃO E COMPARAÇÃO DA ANÁLISE DE ARNETT et al.

Este estudo teve como objetivo aplicar e avaliar a Análise Cefalométrica do Tecido Mole proposta por ARNETT et al. em jovens brasileiros, determinando seus valores médios e comparando com os dos autores. A amostra compôs-se de 60 indivíduos, sendo 24 do sexo masculino e 36 do sexo feminino. Todos brasileiros, leucodermas e portadores de oclusão normal natural, apresentando um mínimo de quatro das seis chaves de oclusão de ANDREWS. A utilização da posição natural da cabeça e da linha vertical verdadeira no momento da obtenção das telerradiografias compuseram a metodologia do trabalho. Avaliaram-se os fatores dentários e os esqueléticos, as espessuras do tecido mole, os comprimentos faciais, as projeções do tecido mole em relação à Linha Vertical Verdadeira e a harmonia intramandibular, a intermaxilar e a facial total. Os resultados demonstraram que os valores médios da amostra estudada apresentaram diferenças em relação aos valores normativos de ARNETT et al. na maioria das variáveis e quando comparados entre si, verificou-se que os americanos apresentaram altura facial maior, perfil facial mais reto e nariz mais proeminente que os brasileiros, tanto para o sexo masculino como para o feminino. O sexo masculino apresentou altura facial e espessura dos tecidos moles maior que o sexo feminino, porem, lábios superior e inferior menos protruídos em relação à Linha Vertical Verdadeira. A

AVALIAÇÃO CEFALOMÉTRICA DO TECIDO MOLE EM JOVENS COM OCLUSÃO NORMAL: APLICAÇÃO E COMPARAÇÃO DA ANÁLISE DE ARNETT et al.

Este estudo teve como objetivo aplicar e avaliar a Análise Cefalométrica do Tecido Mole proposta por ARNETT et al. em jovens brasileiros, determinando seus valores médios e comparando com os dos autores. A amostra compôs-se de 60 indivíduos, sendo 24 do sexo masculino e 36 do sexo feminino. Todos brasileiros, leucodermas e portadores de oclusão normal natural, apresentando um mínimo de quatro das seis chaves de oclusão de ANDREWS. A utilização da posição natural da cabeça e da linha vertical verdadeira no momento da obtenção das telerradiografias compuseram a metodologia do trabalho. Avaliaram-se os fatores dentários e os esqueléticos, as espessuras do tecido mole, os comprimentos faciais, as projeções do tecido mole em relação à Linha Vertical Verdadeira e a harmonia intramandibular, a intermaxilar e a facial total. Os resultados demonstraram que os valores médios da amostra estudada apresentaram diferenças em relação aos valores normativos de ARNETT et al. na maioria das variáveis e quando comparados entre si, verificou-se que os americanos apresentaram altura facial maior, perfil facial mais reto e nariz mais proeminente que os brasileiros, tanto para o sexo masculino como para o feminino. O sexo masculino apresentou altura facial e espessura dos tecidos moles maior que o sexo feminino, porem, lábios superior e inferior menos protruídos em relação à Linha Vertical Verdadeira. A

AVALIAÇÃO CEFALOMÉTRICA DA ESTABILIDADE DO TRATAMENTO COM O REGULADOR DE FUNÇÃO FRÄNKEL-2

O objetivo desta pesquisa consistiu em comparar as alterações dentárias, esqueléticas e tegumentares promovidas pelo aparelho de Fränkel-2 com um grupo controle, além de observar a estabilidade desses efeitos promovidos pelo tratamento, num período médio de 7,11 anos pós-tratamento. A amostra compreendeu um total de 90 telerradiografias em norma lateral, sendo 54 telerradiografias provenientes de 18 pacientes tratados com o RF-2 avaliados em três fases (T1:início de tratamento;T2: final de tratamento e T3: pós-tratamento) e 36 telerradiografias de 18 pacientes-controle, observados em dois tempos. Para comparação entre os grupos tratado e controle foi utilizado o teste t de Student não pareado. Já para a análise dos valores do grupo tratado nos três tempos (T1, T2 e T3) foi utilizada a Análise de Variância (ANOVA) a um critério e o teste de Tukey (p<0,05). As principais alterações proporcionadas pelo aparelho RF-2 observadas a partir da comparação do grupo tratado com o controle envolveram efeitos mandibulares, principalmente a protrusão e aumento do comprimento mandibular associado com uma rotação horária, que resultou em uma maior altura facial total (N-Me) e ântero-inferior (AFAI), além de suave rotação anti-horária do plano palatino (SN.PP). Os incisivos superiores retruíram e o inferior vestibularizou. Houve uma distalização relativa dos molares superiores juntamente com a diminuição do overjet , desta forma a convexidade do perfil facial tegumentar melhorou. No período pós-tratamento (T3) observou-se uma estabilidade sagital de maxila (SNA) e mandíbula (SNB), das variáveis do padrão facial, da inclinação do incisivo superior, do ângulo nasolabial e do overjet . A mandíbula e a maxila continuaram a crescer no sentido antero-posterior, juntamente com as alturas faciais Houve também a extrusão de incisivos e molares. Já o plano oclusal e o ângulo goníaco diminuíram na fase pós-tratamento.(AU)

AVALIAÇÃO CEFALOMÉTRICA DA ESTABILIDADE DO TRATAMENTO COM O REGULADOR DE FUNÇÃO FRÄNKEL-2

O objetivo desta pesquisa consistiu em comparar as alterações dentárias, esqueléticas e tegumentares promovidas pelo aparelho de Fränkel-2 com um grupo controle, além de observar a estabilidade desses efeitos promovidos pelo tratamento, num período médio de 7,11 anos pós-tratamento. A amostra compreendeu um total de 90 telerradiografias em norma lateral, sendo 54 telerradiografias provenientes de 18 pacientes tratados com o RF-2 avaliados em três fases (T1:início de tratamento;T2: final de tratamento e T3: pós-tratamento) e 36 telerradiografias de 18 pacientes-controle, observados em dois tempos. Para comparação entre os grupos tratado e controle foi utilizado o teste t de Student não pareado. Já para a análise dos valores do grupo tratado nos três tempos (T1, T2 e T3) foi utilizada a Análise de Variância (ANOVA) a um critério e o teste de Tukey (p<0,05). As principais alterações proporcionadas pelo aparelho RF-2 observadas a partir da comparação do grupo tratado com o controle envolveram efeitos mandibulares, principalmente a protrusão e aumento do comprimento mandibular associado com uma rotação horária, que resultou em uma maior altura facial total (N-Me) e ântero-inferior (AFAI), além de suave rotação anti-horária do plano palatino (SN.PP). Os incisivos superiores retruíram e o inferior vestibularizou. Houve uma distalização relativa dos molares superiores juntamente com a diminuição do overjet , desta forma a convexidade do perfil facial tegumentar melhorou. No período pós-tratamento (T3) observou-se uma estabilidade sagital de maxila (SNA) e mandíbula (SNB), das variáveis do padrão facial, da inclinação do incisivo superior, do ângulo nasolabial e do overjet . A mandíbula e a maxila continuaram a crescer no sentido antero-posterior, juntamente com as alturas faciais Houve também a extrusão de incisivos e molares. Já o plano oclusal e o ângulo goníaco diminuíram na fase pós-tratamento.(AU)

A new mechanism of sound generation in songbirds

Our current understanding of the sound-generating mechanism in the songbird vocal organ, the syrinx, is based on indirect evidence and theoretical treatments. The classical avian model of sound production postulates that the medial tympaniform membranes (MTM) are the principal sound generators. We tested the role of the MTM in sound generation and studied the songbird syrinx more directly by filming it endoscopically. After we surgically incapacitated the MTM as a vibratory source, zebra finches and cardinals were not only able to vocalize, but sang nearly normal song. This result shows clearly that the MTM are not the principal sound source. The endoscopic images of the intact songbird syrinx during spontaneous and brain stimulation-induced vocalizations illustrate the dynamics of syringeal reconfiguration before phonation and suggest a different model for sound production. Phonation is initiated by rostrad movement and stretching of the syrinx. At the same time, the syrinx is closed through movement of two soft tissue masses, the medial and lateral labia, into the bronchial lumen. Sound production always is accompanied by vibratory motions of both labia, indicating that these vibrations may be the sound source. However, because of the low temporal resolution of the imaging system, the frequency and phase of labial vibrations could not be assessed in relation to that of the generated sound. Nevertheless, in contrast to the previous model, these observations show that both labia contribute to aperture control and strongly suggest that they play an important role as principal sound generators.