Progresión tumoral y búsqueda de nuevas dianas terapéuticas en la familia de tumores del sarcoma de Ewing: función biológica de la caveolina-1

El sarcoma de Ewing es el segundo tumor óseo infantil más frecuente y presenta una alta incidencia de enfermedad metastática. Este tipo de tumores presentan una traslocación génica característica que da origen a una proteína de fusión, normalmente EWS/FLI1. Esta proteína de fusión actúa como factor de transcripción aberrante regulando la expresión de diferentes genes implicados en la iniciación, mantenimiento y progresión del tumor. Nuestro grupo describió como uno de estos genes diana a la caveolina 1 (CAV1) describiendo además su papel determinante en el fenotipo maligno del sarcoma de Ewing, en la tumorigénesis y en la resistencia a apoptosis inducida por quimioterapia. Para investigar el papel concreto de CAV1 en el proceso metastático de este sarcoma, creamos un modelo de baja expresión de CAV1 en líneas celulares de sarcoma de Ewing y determinamos cambios en su capacidad migratoria, invasiva y metastática. En los ensayos in vitro hallamos una menor capacidad migratoria de las células knockdown de CAV1 y una reducción en la expresión de MMP9 y en la actividad de MMP2. La regulación de la actividad de MMP2 parece estar relacionada con la posible regulación que ejerce CAV1 en la función de MT1-MMP, proteína fundamental para la activación de MMP2. Por otro lado, en este estudio proponemos que CAV1 promueve la expresión de MMP9 tanto transcripcionalmente, regulando la vía de señalización ERK1/2, como a nivel post-transcripcional regulando la vía RSK1/rpS6. Además, en los ensayos de metástasis experimental in vivo las células knockdown de CAV1 presentaron una menor incidencia de metástasis pulmonar, hecho que correlacionó con una disminución en la expresión de SPARC, una proteína de adhesión importante en procesos metastáticos. En resumen, nuestros resultados evidencian la importancia de CAV1 en el proceso metastático del sarcoma de Ewing.

Cortical mapping of the neuronal circuits modulating the muscle tone. Introduction to the electrophysiological treatment of the spastic hand.

L’objectiu d’aquest estudi es investigar l’organització cortical junt amb la connectivitat còrtico-subcortical en subjectes sans, com a estudi preliminar. Els mapes corticals s’han fet per TMS navegada, i els punts motors obtinguts s’han exportant per estudi tractogràfic i anàlisi de las seves connexions. El coneixement precís de la localització de l’àrea cortical motora primària i les seves connexions es la base per ser utilitzada en estudis posteriors de la reorganització cortical i sub-cortical en pacients amb infart cerebral. Aquesta reorganització es deguda a la neuroplasticitat i pot ser influenciada per els efectes neuromoduladors de la estimulació cerebral no invasiva.

Neogene antecedents of the modern human hand and its relation to bipedalism

El present projecte s'ha dut a terme a l'American Museum of Natural History (AMNH, New York) entre el 31 de Desembre de 2010 i el 30 de Desembre de 2012. L'objectiu del projecte era elucidar la història evolutiva de la mà humana: traçar els canvis evolutius en la seva forma i proporcions que van propiciar la seva estructura moderna que permet als humans manipular amb precisió. El treball realitzat ha inclòs recol•lecció de dades i anàlisis, redacció de resultats i formació en mètodes analítics específics. Durant aquest temps, l'autor a completat la seva de base de dades existent en mesures lineals de la mà a hominoides. També s'han agafat dades del peu; d'aquesta forma ara mateix es compta amb una base de dades amb més de 500 individus, amb més de 200 mesures per cada un. També s'han agafat dades en tres imensions utilitzant un làser escàner. S'han après tècniques de morfometria geomètrica 3D directament dels pioners al camp a l'AMNH. Com a resultat d'aquesta feina s'han produït 10 resums (publicats a congressos internacionals) i 9 manuscrits (molts d'ells ja publicats a revistes internacionals) amb resultats de gran rellevància: La mà humana posseeix unes proporcions relativament primitives, que són més similars a les proporciones que tenien els hominoides fòssils del Miocè que no pas a la dels grans antropomorfs actuals. Els darrers tenen unes mans allargades amb un polzes molt curts que reflexen l'ús de la mà com a eina de suspensió sota les branques. En canvi, els hominoides del Miocè tenien unes mans relativament curtes amb un polze llarg que feien servir per estabilitzar el seu pes quan caminaven per sobre de les branques. Una vegada els primers homínids van aparèixer al final del Miocè (fa uns 6 Ma) i van començar a fer servir el bipedisme com a mitjà més comú de locomoció, les seves mans van ser "alliberades" de les seves funcions locomotores. La selecció natural—ara només treballant en la manipulació—va convertir les proporcions ja existents de la mà d'aquests primats en l'òrgan manipulatori que representa la mà humana avui dia.

Tracking the invisible hand: Convergence of double auctions to competitive equilibrium

Economics is the science of want and scarcity. We show that want andscarcity, operating within a simple exchange institution (double auction),are sufficient for an economy consisting of multiple inter--related marketsto attain competitive equilibrium (CE). We generalize Gode and Sunder's(1993a, 1993b) single--market finding to multi--market economies, andexplore the role of the scarcity constraint in convergence of economies to CE.When the scarcity constraint is relaxed by allowing arbitrageurs in multiple markets to enter speculative trades, prices still converge to CE,but allocative efficiency of the economy drops. \\Optimization by individual agents, often used to derive competitive equilibria,are unnecessary for an actual economy to approximately attain such equilibria.From the failure of humans to optimize in complex tasks, one need not concludethat the equilibria derived from the competitive model are descriptivelyirrelevant. We show that even in complex economic systems, such equilibriacan be attained under a range of surprisingly weak assumptions about agentbehavior.

Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures.

Objective: To analyse whether bone mineral density (BMD) assessment is required in postmenopausal women presenting with low trauma vertebral fracture. Methods: Women with vertebral fracture diagnosed over a 10 year period were recruited from our database. The following were excluded: (a) patients with high energy trauma; (b) patients with malignancies; (c) patients with a metabolic bone disease other than osteoporosis. All postmenopausal women were included in whom BMD had been evaluated at both the lumbar spine and femoral neck by dual energy x ray absorptiometry during the six months after the diagnosis. Patients with a potential cause of osteoporosis other than age and menopause were not considered. A total of 215 patients were identified. Results: The mean (SD) age of the patients was 65.9 (6.9) years. BMD at the lumbar spine was 0.725 (0.128) g/cm2 and the T score was ¿2.94 (1.22); BMD at the femoral neck was 0.598 (0.095) g/cm2 and the T score was ¿2.22 (0.89). The BMD of the patients was significantly lower than that of the general population at both the lumbar spine and femoral neck. When the lowest value of the two analysed zones was considered, six patients (3%) showed a normal BMD, 51 (23.5%) osteopenia, and 158 (73.5%) osteoporosis. The prevalence of osteoporosis at the femoral neck increased with age; it was 25% in patients under 60, 35% in patients aged 60¿70, and 60% in patients over 70. Conclusion: These results indicate that bone densitometry is not required in postmenopausal women with clinically diagnosed vertebral fractures if it is performed only to confirm the existence of a low BMD.

Munchausen's syndrome simulating reflex sympathetic dystrophy

A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admissions to hospital and multiple explorations we discovered that she had induced her symptoms herself and a diagnosis of Munchausen's syndrome was made. As far as we know this presentation has not been previously reported and might help to explain the physiopathology of some signs of reflex sympathetic dystrophy.

Value of clinical factors in selecting postmenopausal women with rheumatoid arthritis for bone densitometry.

Criteria to decide which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) are currently not available. The rheumatologists from Amsterdam have proposed preliminary criteria based on clinical risk factors (age, disease activity, and functional status). These criteria are preliminary and not widely accepted but might be helpful in practice. The value of the proposal in a group of Spanish postmenopausal women with RA is analysed. METHODS DXA (lumbar spine and femoral neck) was performed in 128 patients recruited from a clinical setting, and the proposed criteria were applied. T and Z scores were established for a Spanish reference population. RESULTS The mean (SD) age of the patients was 61.3 (10.7) and mean duration of the postmenopausal period 14.5 (10.1) years. Mean duration of RA was 13.7 (7.7) years. Mean C reactive protein was 22 (21) mg/l; mean erythrocyte sedimentation rate 26 (18) mm/1st h; and mean Health Assessment Questionnaire score 1.25 (0.79). Ninety (70%) patients fulfilled the proposed criteria. Their sensitivity for the diagnosis of osteoporosis (T score ¿¿2.5 SD) was 86% and their specificity, 43%. Positive predictive value was 54% and negative predictive value, 79%. CONCLUSIONS The proposed criteria seem a good screening method for the selection of those patients with RA whose bone mineral density should be assessed as the sensitivity and negative predictive value are acceptable.

Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis: a comparative study

A comparative study of the parts played by technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis is presented. Nineteen patients were included in the study. All patients (11 men aged 19-70 years and eight women aged 18-72 years) had a history of back pain varying in duration from one to 15 weeks. A 99mTc diphosphonate bone scan was positive in 17 patients. The two patients with negative results had less than two weeks of back pain. The 67Ga citrate bone scan showed uptake in all patients.

Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis: a comparative study

A comparative study of the parts played by technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis is presented. Nineteen patients were included in the study. All patients (11 men aged 19-70 years and eight women aged 18-72 years) had a history of back pain varying in duration from one to 15 weeks. A 99mTc diphosphonate bone scan was positive in 17 patients. The two patients with negative results had less than two weeks of back pain. The 67Ga citrate bone scan showed uptake in all patients.

Advances in medical imaging applied to bone metastases

Bone metastases are the result of a primary cancer invasion which spreads into the bone marrow through the lymphogenous or hematogenous pathways. Bone metastases are a common complication of cancer.The primary cancers that most frequently metastasize to bone are breast and prostate cancer (65 - 75 %) amongst many others (thyroid 42 %, lung 36 % or kidney 35 %) (Suva et al., 2011). Although the exact incidence of bone metastases is unknown given its dependence on the type of primary cancer, it is estimated that 350,000 people die of bone metastases annually in the United States.

Hand detection in cluttered scene images using Fourier-Mellin invariant features

This paper proposes an automatic hand detection system that combines the Fourier-Mellin Transform along with other computer vision techniques to achieve hand detection in cluttered scene color images. The proposed system uses the Fourier-Mellin Transform as an invariant feature extractor to perform RST invariant hand detection. In a first stage of the system a simple non-adaptive skin color-based image segmentation and an interest point detector based on corners are used in order to identify regions of interest that contains possible matches. A sliding window algorithm is then used to scan the image at different scales performing the FMT calculations only in the previously detected regions of interest and comparing the extracted FM descriptor of the windows with a hand descriptors database obtained from a train image set. The results of the performed experiments suggest the use of Fourier-Mellin invariant features as a promising approach for automatic hand detection.