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.

Acute Damage to the Posterior Limb of the Internal Capsule on Diffusion Tensor Tractography as an Early Imaging Predictor of Motor Outcome after Stroke

Background and Purpose Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. Methods We evaluated 60 consecutive patients within 12 hours of MCA stroke onset. We used DTT to evaluate CST involvement in the MC and PMC, CS, CR, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed using the m-NIHSS (5a, 5b, 6a, 6b). We calculated volumes of infarct and FA values in the CST of the pons. Results Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P&.001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P=.176, r=0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for 4 motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R2=75.50, F=80.09, P&.001). Conclusions In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

The v-y latissimus dorsi musculocutaneous flap in the reconstruction of large posterior chest wall defects.

Posterior chest wall defects are frequently encountered after excision of tumors as a result of trauma or in the setting of wound dehiscence after spine surgery. Various pedicled fasciocutaneous and musculocutaneous flaps have been described for the coverage of these wounds. The advent of perforator flaps has allowed the preservation of muscle function but their bulk is limited. Musculocutaneous flaps remain widely employed. The trapezius and the latissimus dorsi (LD) flaps have been used extensively for upper and middle posterior chest wounds, respectively. Their bulk allows for obliteration of the dead space in deep wounds. The average width of the LD skin paddle is limited to 10-12 cm if closure of the donor site is expected without skin grafting. In 2001 a modification of the skin paddle design was introduced in order to allow large flaps to be raised without requiring grafts or flaps for donor site closure. This V-Y pattern allows coverage of large anterior chest defects after mastectomy. We have modified this flap to allow its use for posterior chest wall defects. We describe the flap design, its indications, and its limitations with three clinical cases. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .

Actividad de la vía PI3K-AKT-FOXOp27 como factor pronóstico en tumores astrocitarios

Els tumors astrocitaris són entitats poc freqüents i el seu pronòstic és pobre. Recentment s'ha descrit l'alta freqüència d'alteració de la via de PI3K a aquests tumors. L'objectiu d'aquest estudi és valorar la possible correlació entre la supervivència lliure de progressió d'una sèrie de pacients intervinguts per tumors astrocitarios en el nostre centre i l'activació de la via de PI3K definida mitjançant expressió inmunohistoquímica. Es van analitzar un total de 83 pacients. A més dels factors correlacionats en la literatura amb la supervivència lliure de progressió (grau, cirurgia i edat), l'estudi mostra una correlació directament proporcional amb els nivells de pFOXO i inversament proporcional amb p27. El valor d'aquestes troballes haurà de ser validat posteriorment.

Stress radiography and posterior pathological laxity of knee: comparison between two different techniques.

Stress radiographs have been recommended in order to obtain a better objective quantification of abnormal compartment knee motion. This tool has showed to be superior in quantifying a posterior cruciate ligament (PCL) lesion compared to clinical or arthrometer evaluation. Different radiographic techniques have been described in literature to quantify posterior pathological laxity. In this study we evaluated the total amount of posterior displacement (PTD) and side to side difference (SSD), before and after surgical reconstruction of PCL or PCL and posterolateral complex (PLC), using two different stress radiography techniques (Telos stress and kneeling view). Twenty patients were included in this study. We found a statistical significant difference about both total PTD and SSD among the two techniques preoperatively and at follow-up, with greatest values occurring using the kneeling view. Although stress radiographies has been introduced to allow an objective quantification of laxity in ligamentous injured knee, we believe that further studies on a large numbers of subjects are required to define the relationship between PTD values, measured with stress knee radiography, particularly using kneeling view, and ligamentous knee injury, in order to obtain a real useful tool in the decision making process, as well as to evaluate the outcome after ligamentous surgery.

Effect of blood components, abdominal distension, and ecdysone therapy on the ultrastructural organization of posterior midgut epithelial cells and perimicrovillar membranes in Rhodnius prolixus

The effects of blood components, nerve-cord severance, and ecdysone therapy on the posterior midgut epithelial cells of 5th-instar Rhodnius prolixus nymphs 10 days after feeding were analyzed by transmission electron microscopy. Cutting the nerve-cord of the blood-fed insects partially reduced the development of microvilli and perimicrovillar membranes (PMM), and produced large vacuoles and small electrondense granules; insects fed on Ringer's saline diet exhibited well developed microvilli and low PMM production; swolled rough endoplasmatic reticulum and electrondense granules; Ringer's saline meal with ecdysone led to PMM development, glycogen particles, and several mitochondria in the cytoplasm; epithelial cells of the insects fed on Ringer's saline meal whose nerve-cord was severed showed heterogeneously distributed microvilli with reduced PMM production and a great quantity of mitochondria and glycogen in the cytoplasm; well developed microvilli and PMM were observed in nerve-cord severed insects fed on Ringer's saline meal with ecdysone; Ringer's saline diet containing hemoglobin recovered the release of PMM; and insects fed on human plasma showed slightly reduced PMM production, although the addition of ecdysone in the plasma led to a normal midgut ultrastructural organization. We suggest that the full development of microvilli and PMM in the epithelial cells depends on the abdominal distension in addition to ingestion of hemoglobin, and the release of ecdysone.

Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii

It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT) is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007). There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001). ELISA test sensitivity was 84% and specificity 78% . Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment

Introduction: Accurate registration of the relative timing between the occurrence of sensory events on a sub-second time scale is crucial for both sensory-motor and cognitive functions (Mauk and Buonomano, 2004; Habib, 2000). Support for this assumption comes notably from evidence that temporal processing impairments are implicated in a range of neurological and psychiatric conditions (e.g. Buhusi & Meck, 2005). For instance, deficits in fast auditory temporal integration have been regularly put forward as resulting in phonologic discrimination impairments at the basis of speech comprehension deficits characterizing e.g. dyslexia (Habib, 2000). At least two aspects of the brain mechanisms of temporal order judgment remain unknown. First, it is unknown when during the course of stimulus processing a temporal ,,stamp‟ is established to guide TOJ perception. Second, the extent of interplay between the cerebral hemispheres in engendering accurate TOJ performance is unresolved Methods: We investigated the spatiotemporal brain dynamics of auditory temporal order judgment (aTOJ) using electrical neuroimaging analyses of auditory evoked potentials (AEPs) recorded while participants completed a near-threshold task requiring spatial discrimination of left-right and right-left sound sequences. Results: AEPs to sound pairs modulated topographically as a function of aTOJ accuracy over the 39-77ms post-stimulus period, indicating the engagement of distinct configurations of brain networks during early auditory processing stages. Source estimations revealed that accurate and inaccurate performance were linked to bilateral posterior sylvian regions activity (PSR). However, activity within left, but not right, PSR predicted behavioral performance suggesting that left PSR activity during early encoding phases of pairs of auditory spatial stimuli appears critical for the perception of their order of occurrence. Correlation analyses of source estimations further revealed that activity between left and right PSR was significantly correlated in the inaccurate but not accurate condition, indicating that aTOJ accuracy depends on the functional de-coupling between homotopic PSR areas. Conclusions: These results support a model of temporal order processing wherein behaviorally relevant temporal information - i.e. a temporal 'stamp'- is extracted within the early stages of cortical processes within left PSR but critically modulated by inputs from right PSR. We discuss our results with regard to current models of temporal of temporal order processing, namely gating and latency mechanisms.

Proyecto para la identificación de necesidades formativas y posterior implementación de acción docente en el ERIE Psicosocial de C.R.N.

La responsabilidad del ERIE Psicosocial a la hora de realizar su labor en el marco de la intervención en emergencias debe ir necesariamente acompañada de una correcta identificación de las necesidades que el equipo tiene en lo que respecta a su formación e instrucción, de cara a mantener el nivel de respuesta en su labor. El desarrollo de herramientas y métodos capaces de definir estas variables es, pues el primer paso de este proceso. El formato de desarrollo posterior de esas acciones formativas, teniendo en cuenta el carácter grupal y cooperativo del grupo, debe ser estudiado y validado para obtener la máxima eficacia durante su materialización.

Proyecto para la identificación de necesidades formativas y posterior implementación de acción docente en la Unidad de Salud y Socorros de Cruz Roja Pamplona

Proyecto orientado a identificar aspectos mejorables desde el punto de vista formativo en la labor desarrollada por el voluntariado dedicado a la emergencia extra-hospitalaria.

Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes.

BACKGROUND: The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. RESULTS: We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff < or = 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p < or = 0.05) along the anterior-posterior axis was observed. CONCLUSION: All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.

Projecte de trasllat de l’ explotació de boví de llet “Mas Masdevall” a Olot

L’ objectiu principal d’ aquest projecte és el de dissenyar una nova explotació de boví de llet a lagranja “Mas Masdevall”, a Olot, comarca de la Garrotxa, província de Girona, per tal de traslladar l’explotació existent a una ubicació més allunyada; a més d’aquest canvi d’ubicació, també s’augmentarà el nombre de vaques de la granja de les 80 originals a una capacitat total de 120 vaques en producció. Aquest projecte planteja la construcció d’una nau per a l’allotjament de les vaques en producció, una sala de munyir-lleteria, un femer i una fossa de purins. La nau de producció tindrà una capacitat per a 120 vaques en producció en llotges individuals, 7 places d’infermeria, 7 per maternitat, 12 vaques eixutes totes en jaç de palla, a més de 51 places per vedelles en jaç i un lot de 22 vedelles d’entre 16 i 22 mesos en llotges individuals per facilitar la posterior estabulació durant la producció. També s’ubicaran 14 boxes individuals per els vedells i la recria al costat de la nau. La sala de munyir serà de 2x10 places paral·leles a més de la sala d’espera i l’oficina lleteria

Avaluació de programes formatius de seguretat viària i la reincidència posterior

Els programes formatius d’educació viària són una mesura penal alternativa que s’imposa habitualment als autors dels delictes relacionats amb el trànsit (articles 379 i següents del Codi Penal) per suspendre o substituir la pena de presó. Aquests programes tenen un doble objectiu: aconseguir reduir a curt termini la sinistralitat viària i propiciar un canvi cultural permanent en la conducció. L’objectiu principal d’aquesta recerca va ser identificar les característiques comunes dels infractors de trànsit que fan aquest tipus d’intervenció, conèixer els factors de risc associats a aquests infractors i en quina mesura l’estat psicològic és un factor de risc en l’estil de conducció. També es volia determinar si hi havia diferències entre les entitats que impartien la formació, avaluar l’efectivitat d’aquests programes en l’estil de conducció dels participants en finalitzar el curs i conèixer la reincidència dels seus participants i la seva relació amb l’estat i el canvi de les variables de l’estudi. La mostra va comptar amb 278 participants voluntaris del total de 354 infractors de trànsit que van realitzar un programa formatiu entre l’1 d’abril de 2009 i el 13 de febrer de 2010. D’aquests, un total de 100 participants van autoritzar a ser contactats novament entre el desembre del 2011 i el gener del 2012, per mirar la reincidència. Les fonts d’informació van ser els qüestionaris passats als infractors i el buidatge de la base de dades d’execució penal del Departament de Justícia, amb informació judicial i personal i el seguiment dels usuaris fins a dos anys després d’haver finalitzat el curs formatiu, per saber si havien tornat a reincidir en el mateix delicte.

Evaluación de programas formativos de seguridad vial y su reincidencia posterior

Los programas formativos de educación vial son una medida penal alternativa que se impone habitualmente a los autores de delitos relacionados con el tráfico (artículos 379 y siguientes del Código Penal) para suspender o sustituir la pena de prisión. Estos programas tienen un doble objetivo: conseguir reducir a corto plazo la siniestralidad vial y propiciar un cambio cultural permanente en la conducción. El objetivo principal de esta investigación fue identificar las características comunes de los infractores de tráfico que han de hacer este tipo de intervención y conocer sus factores de riesgo. También se estudiaron las diferencias entre las entidades que imparten los cursos formativos, se evaluó su efectividad y se estudió la reincidencia de los conductores. En total participaron 278 infractores que realizaron un programa formativo entre el 1 de abril de 2009 y el 13 de febrero de 2010 y se les siguió hasta enero de 2012.

Artrodesis posterior C1-C2. Resultados y comparación de la fijación transarticular e interarticular en una serie de 36 pacientes

Objetivo. Analizar los resultados de la fijación transarticular e interarticular en dos series de pacientes. Métodos. Se analizaron 36 pacientes con inestabilidad C1-C2, 20 tratados mediante fijación transarticular, y 15 con fijación interarticular. Se obtuvieron datos sobre las complicaciones, evolución radiológica y resultados clínicos. Resultados. De los tratados con fijación transarticular se obtuvieron resultados buenos en 17 casos, regular en 2 y malo en 1. En la fijación interarticular en 14 se obtuvieron un buen resultado, y regular en 2. Conclusiones. La fijación C1-C2 transarticular e interarticular resulta segura, con presentando altas tasas de buenos resultados con pocas complicaciones.