99 research outputs found

    Towards an in-plane methodology to track breast lesions using mammograms and patient-specific finite-element simulations

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    In breast cancer screening or diagnosis, it is usual to combine different images in order to locate a lesion as accurately as possible. These images are generated using a single or several imaging techniques. As x-ray-based mammography is widely used, a breast lesion is located in the same plane of the image (mammogram), but tracking it across mammograms corresponding to different views is a challenging task for medical physicians. Accordingly, simulation tools and methodologies that use patient-specific numerical models can facilitate the task of fusing information from different images. Additionally, these tools need to be as straightforward as possible to facilitate their translation to the clinical area. This paper presents a patient-specific, finite-element-based and semi-automated simulation methodology to track breast lesions across mammograms. A realistic three-dimensional computer model of a patient''s breast was generated from magnetic resonance imaging to simulate mammographic compressions in cranio-caudal (CC, head-to-toe) and medio-lateral oblique (MLO, shoulder-to-opposite hip) directions. For each compression being simulated, a virtual mammogram was obtained and posteriorly superimposed to the corresponding real mammogram, by sharing the nipple as a common feature. Two-dimensional rigid-body transformations were applied, and the error distance measured between the centroids of the tumors previously located on each image was 3.84 mm and 2.41 mm for CC and MLO compression, respectively. Considering that the scope of this work is to conceive a methodology translatable to clinical practice, the results indicate that it could be helpful in supporting the tracking of breast lesions

    Aplicación de aleaciones con memoria de forma en el diseño y fabricación de ferulajes para corrección de las deformidades articulares de los dedos de la mano

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    OBJETIVO: Se propone un prototipo de férula para la corrección de las deformidades articulares de los dedos de la mano, basados en las propiedades de las aleaciones de níquel-titanio, con el fin de mejorar la aplicación de las ortesis dinámicas de acción constante, empleadas habitualmente en ortopedia. MATERIAL Y MÉTODOS: Para ello, se han diseñado diferentes prototipos de láminas y varillas, variando sus grosores. Los prototipos se han aplicado a 15 pacientes con su consentimiento, deformidad en Boutonnière, entre 40 y 60º de angulación de la articulación interfalángica proximal (IFP) del dedo y edades comprendidas entre 18 y 39 años (media 31 años), midiendo cuando empieza a notarse un cambio en la fuerza tensil de la férula sobre la deformidad del dedo con el equipo Xpresion. RESULTADOS: Los valores obtenidos, son de 3291,67 ± 222,30 gr./mm 2, guardando relación directa con el diámetro del dedo. Los resultados obtenidos hasta conseguir una corrección superior al 75 %, han sido buenos en 9 pacientes, 5 regulares (corrección entre 30 % y 75 %) y uno malo (inferior al 30 %). CONCLUSIONES: Las férulas de Níquel Titanio con tensiones constantes durante largos periodos de tiempo, hasta recuperar la posición original, con su diseño, mejoran el ajuste inicial facilitando el manejo por parte del paciente y del especialista.Peer Reviewe

    Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

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    Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

    A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms

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    Electron microscopy (EM) achieves the highest spatial resolution in protein localization, but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues. Here we introduce “miniSOG” (for mini Singlet Oxygen Generator), a fluorescent flavoprotein engineered from Arabidopsis phototropin 2. MiniSOG contains 106 amino acids, less than half the size of Green Fluorescent Protein. Illumination of miniSOG generates sufficient singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by EM. MiniSOG fusions to many well-characterized proteins localize correctly in mammalian cells, intact nematodes, and rodents, enabling correlated fluorescence and EM from large volumes of tissue after strong aldehyde fixation, without the need for exogenous ligands, probes, or destructive permeabilizing detergents. MiniSOG permits high quality ultrastructural preservation and 3-dimensional protein localization via electron tomography or serial section block face scanning electron microscopy. EM shows that miniSOG-tagged SynCAM1 is presynaptic in cultured cortical neurons, whereas miniSOG-tagged SynCAM2 is postsynaptic in culture and in intact mice. Thus SynCAM1 and SynCAM2 could be heterophilic partners. MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy
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