RS-0406 arrests amyloid-B oligomer-induced behavioural deterioration in vivo

Clinically accessible compounds that arrest or reverse the effects of amyloid-ß (Aß) on progressively developing behavioural symptomatology and neuropathology in Alzheimer's disease (AD) have yet to become available. However, a viable strategy may be to target and neutralise soluble Aß oligomers, which have been shown to mediate synaptic dysfunction and to produce cognitive deficits in the intact organism. Inhibiting the aggregation of Aß is therapeutically attractive, as Aß aggregation is a pathological event and pharmacological interventions targeting this are likely to have a non-toxic profile. A behavioural assay, the alternating-lever cyclic-ratio schedule, was used to assess the effect of Aß oligomers and the non-peptide small molecule RS-0406 in male Sprague-Dawley rats. RS-0406 has been shown to inhibit Aß1-42 fibrillogenesis and protect against Aß1-42–induced cytotoxicity in primary hippocampal neurons. In the current study, RS-0406 ameliorated the adverse effects of secreted oligomers of human Aß on behaviour and dose dependently reduced the behavioural effects of Aß oligomers, with the highest dose, 10 µM, maintaining behaviour approximately at control levels. This effect appeared to be central; peripheral confounds having been extensively investigated. This is the first published report on the effects of RS-0406 in vivo and indicates that RS-0406 has potential as a pharmacotherapeutic intervention for behavioural deficits seen in the early stages of AD, and possibly as an intervention in the development of AD neuropathology. Indeed, an analogue of RS-0406 that could be administered peripherally might be a realistic candidate for the clinical treatment of AD.

The Hybrid Approach for Palliation of Hypoplastic Left Heart Syndrome: Intermediate Results of a Single-Center Experience

INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is a major cause of cardiac death during the first week of life. The hybrid approach is a reliable, reproducible treatment option for patients with HLHS. Herein we report our results using this approach, focusing on its efficacy, safety and late outcome. METHODS: We reviewed prospectively collected data on patients treated for HLHS using a hybrid approach between July 2007 and September 2014. RESULTS: Nine patients had a stage 1 hybrid procedure, with seven undergoing a comprehensive stage 2 procedure. One patient completed the Fontan procedure. Five patients underwent balloon atrial septostomy after the hybrid procedure; in three patients, a stent was placed across the atrial septum. There were three deaths: two early after the hybrid procedure and one early after stage two palliation. Overall survival was 66%. CONCLUSIONS: In our single-center series, the hybrid approach for HLHS yields intermediate results comparable to those of the Norwood strategy. The existence of dedicated teams for the diagnosis and management of these patients, preferably in high-volume centers, is of major importance in this condition.

Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation

An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy.

Indirect Bonding Method: in vitro Comparison of the Shear Bond Strength between Metallic Orthodontic Brackets and Different Porcelain Surface Preparations

Introduction : La force d’adhésion à l'interface métal-céramique avec les résines auto-polymérisantes destinées au collage indirect des boîtiers orthodontiques n'a pas été évaluée à ce jour et un protocole clinique basé sur la littérature scientifique est inexistant. Objectifs : 1) Comparer la force de cisaillement maximale entre des boîtiers métalliques et des surfaces en porcelaine préparées selon différentes méthodes; 2) Suggérer un protocole clinique efficace et prévisible. Matériel et méthodes : Quatre-vingt-dix disques en leucite (6 groupes; n = 15/groupe) ont été préparés selon 6 combinaisons de traitements de surface : mécaniques (+ / - fraisage pour créer les rugosités) et chimiques (acide fluorhydrique, apprêt, silane). Des bases en résine composite Transbond XT (3M Unitek, Monrovia, California) faites sur mesure ont été collées avec le système de résine adhésive auto-polymérisante Sondhi A + B Rapid Set (3M Unitek, Monrovia, California). Les échantillons ont été préservés (H2O/24hrs), thermocyclés (500 cycles) et testés en cisaillement (Instron, Norwood, Massachusetts). Des mesures d’Index d’adhésif résiduel (IAR) ont été compilées. Des tests ANOVAs ont été réalisés sur les rangs étant donné que les données suivaient une distribution anormale et ont été ajustés selon Tukey. Un Kruskall-Wallis, U-Mann Whitney par comparaison pairée et une analyse de Weibull ont aussi été réalisés. Résultats : Les médianes des groupes varient entre 17.0 MPa (- fraisage + acide fluorhydrique) à 26.7 MPa (- fraisage + acide fluorhydrique + silane). Le fraisage en surface ne semble pas affecter l’adhésion. La combinaison chimique (- fraisage + silane + apprêt) a démontré des forces de cisaillement significativement plus élevées que le traitement avec (- fraisage + acide fluorhydrique), p<0,05, tout en possédant des forces similaires au protocole typiquement suggéré à l’acide fluorhydrique suivi d’une application de silane, l’équivalence de (- fraisage + acide fluorhydrique + silane). Les mesures d’IAR sont significativement plus basses dans le groupe (- fraisage + acide fluorhydrique) en comparaison avec celles des 5 autres groupes, avec p<0,05. Malheureusement, ces 5 groupes ont des taux de fracture élévés de 80 à 100% suite à la décimentation des boîtiers. Conclusion : Toutes les combinaisons de traitement de surface testées offrent une force d’adhésion cliniquement suffisante pour accomplir les mouvements dentaires en orthodontie. Une application de silane suivie d’un apprêt est forte intéressante, car elle est simple à appliquer cliniquement tout en permettant une excellente adhésion. Il faut cependant avertir les patients qu’il y a un risque de fracture des restorations en céramique lorsque vient le moment d’enlever les broches. Si la priorité est de diminuer le risque d’endommager la porcelaine, un mordançage seul à l’acide hydrofluorique sera suffisant.

Curva de aprendizaje para ventana ecográfica de la vena cava inferior, en residentes de medicina de emergencias

INTRODUCCIÓN. El ultrasonido es fundamental en la medicina de emergencias, no se conoce cual debería ser la curva de aprendizaje para obtener las competencias técnicas y operativas; ACEP recomienda por cada ventana ecográfica realizar 25 repeticiones. No existe una curva de aprendizaje para ventana de VCI en la población de residentes colombianos. OBJETIVO: Determinar la curva de aprendizaje necesaria para obtener una proporción mayor al 80% de éxitos en la toma de la ventana ecográfica de la VCI, usando la escala de calificación para el aseguramiento de la calidad sugerida por ACEP, en residentes de I a III año de medicina de emergencias. METODOLOGÍA: Estudio experimental no comparativo, que evaluó la proporción de éxito en función del las tomas repetidas de la VCI por ultrasonido, mediciones que se tomaron luego de participar en una capacitación teórica y demostrativa de la técnica propuesta; se calificaron los videos según la escala publicada por ACEP. El análisis estadístico se realizó con un modelo logístico multinivel para la proporción del éxito, agrupado por repetición y agrupado por sujeto. RESULTADOS: Se obtuvo información de 8 residentes, cada uno realizo 25 repeticiones a 3 modelos sanos con asignación aleatoria. Se realizó la curva de aprendizaje obteniendo en 11 repeticiones una proporción de 0.80 (rango 0.54 a 0.92) y en 21 repeticiones una proporción de 0.9 (rango 0.75 a 0.96), datos ajustados por numero de repetición y residente. CONCLUSIÓN: La curva de aprendizaje para la ventana ecográfica de la VCI es de 11 y 21 repeticiones para obtener el 80% y 90% de éxito en residentes de medicina de emergencias de I a III año de la universidad del rosario.

Definition of an it project portfolio management methodology for a pharmaceutical company

Con la creciente popularidad de las soluciones de IT como factor clave para aumentar la competitividad y la creación de valor para las empresas, la necesidad de invertir en proyectos de IT se incrementa considerablemente. La limitación de los recursos como un obstáculo para invertir ha obligado a las empresas a buscar metodologías para seleccionar y priorizar proyectos, asegurándose de que las decisiones que se toman son aquellas que van alineadas con las estrategias corporativas para asegurar la creación de valor y la maximización de los beneficios. Esta tesis proporciona los fundamentos para la implementación del Portafolio de dirección de Proyectos de IT (IT PPM) como una metodología eficaz para la gestión de proyectos basados en IT, y una herramienta para proporcionar criterios claros para los directores ejecutivos para la toma de decisiones. El documento proporciona la información acerca de cómo implementar el IT PPM en siete pasos, el análisis de los procesos y las funciones necesarias para su ejecución exitosa. Además, proporciona diferentes métodos y criterios para la selección y priorización de proyectos. Después de la parte teórica donde se describe el IT PPM, la tesis aporta un análisis del estudio de caso de una empresa farmacéutica. La empresa ya cuenta con un departamento de gestión de proyectos, pero se encontró la necesidad de implementar el IT PPM debido a su amplia cobertura de procesos End-to-End en Proyectos de IT, y la manera de asegurar la maximización de los beneficios. Con la investigación teórica y el análisis del estudio de caso, la tesis concluye con una definición práctica de un modelo aproximado IT PPM como una recomendación para su implementación en el Departamento de Gestión de Proyectos.

Ergonomía. Fundamentos para el desarrollo de soluciones ergonómicas

En este texto se presentan algunos conceptos y marcos teóricos útiles para el análisis del trabajo en ergonomía. El objetivo es mostrar los conceptos de base para el estudio del trabajo en la tradición de la ergonomía de la actividad, y analizar de manera general algunos de los modelos empleados para el análisis de una actividad de trabajo. Inicialmente se abordan los principios teóricos de la ergonomía y los principios que provienen de la fisiología, la biomecánica, la psicología y la sociología; también se presentan los acercamientos metodológicos empleados en esta misma perspectiva para el análisis de actividades de trabajo. Se parte del principio de que un estudio ergonómico del trabajo se puede llevar a cabo desde una doble perspectiva: la perspectiva analítica y la perspectiva comprensiva.

Pruebas y exámenes en Inglaterra.

La enseñanza media en Inglaterra en 1939 se aprobaba mediante un examen llamado School Certificate y duraba cinco años. Puede decirse que de cada cien niños de las escuelas primarias sólo cinco pasaban a estudiar un curso completo de segunda enseñanza y solamente uno, llegaba hasta la universidad.. No debe olvidarse que en Inglaterra la educación superior se hallaba sujeta a un proceso selectivo muy elevado. Se consideró como un gran avance en la cuestión docente que la posesión de este certificado eximiese a su poseedor de todos los exámenes de ingreso y pruebas de este tipo, siempre que la nota obtenida fuese superior fuese superior al simple aprobado. De esta forma, dicho examen entorpecía todo el desarrollo de la enseñanza media al imponer un tipo de instrucción que no era apto para la mayoría, desde el momento que una tercera parte de los estudiantes nunca llegaba al final del curso, y otra tercera, no conseguía aprobar.

In Vitro Biomechanical Evaluation of the Use of Conventional and Locking Miniplate/Screw Systems for Sagittal Split Ramus Osteotomy

Purpose: The aim of this in vitro study was to assess the biomechanical stability of 9 different osteosynthesis methods after sagittal split ramus osteotomy by simulating the masticatory forces and using a 3-point biomechanical test method.Materials and Methods: Forty-five polyurethane hemimandibles with bone-like consistency were randomly assigned to 9 groups (n = 5) and subjected to sagittal split ramus osteotomy. After 4-mm advancement of the distal segment, the bone segments were fixed by different osteosynthesis methods using 2.0-mm miniplate/screw systems: group A, one 4-hole conventional straight miniplate; group B, one 4-hole locking straight miniplate; group C, one 4-hole conventional miniplate and one bicortical screw; group D, one 4-hole locking miniplate and 1 bicortical screw; group E, one 6-hole conventional straight miniplate; group F, one 6-hole locking straight miniplate; group (3: two 4-hole conventional straight miniplates; group H. two 4-hole locking straight miniplates; and group 1, 3 bicortical screws in an inverted-L. pattern. All models were mounted on a base especially constructed for this purpose. Using a 3-point biomechanical test model, the hemimandibles were loaded in compressive strength in an Instron machine (Norwood, MA) until a 3-mm displacement occurred between segments vertically or horizontally. Data were analyzed by analysis of variance and Tukey test (alpha = 1%).Results: The multiparametric comparison of the groups showed a statistically significant difference (P<.01) between groups that used 2 miniplates (groups G and H), 1 miniplate and 1 bicortical screw (groups C and D), and only bicortical screws (group D compared with groups that used only 1 miniplate with 2 screws per segment (groups A and B) and 3 screws per segment (groups E and F).Conclusion: The placement of 2.0-mm-diameter bicortical screws in the retromolar region, associated or not with conventional and locking miniplates with monocortical screws, promoted a better stabilization of bone segments. Locking miniplates presented a better performance in bone fixation in all groups. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:724-730, 2010

Comparative Study of the Mechanical Resistance of 2 Separate Plates and 2 Overlaid Plates Used in the Fixation of the Mandibular Condyle: An In Vitro Study

Purpose: The objective of this study was to carry out a comparative evaluation of the mechanical resistance of 2 rigid internal fixation techniques for fractures of the mandibular condyle using miniplates.Materials and Methods: Fort), polyurethane resin replicas of human hemimandibles were used. The hemimandibles were sectioned to simulate a high subcondylar fracture and then stabilized with 2 fixing techniques using 2.0-mm system plates and screws. The fixation techniques were 2 separate 4-hole plates with 8 screws, and 2 overlaid 4-hole plates with 4 screws. Each system was submitted to load tests, with the application of the load in mediolateral and anteroposterior directions in an Instron 4411 universal assay machine (Instron, Norwood, MA).Results: Load values and peak displacement were measured. Means and standard deviations were evaluated by analysis of variance (P < .05) and Tukey tests, in which it was verified that the anteroposterior peak load value was affected by the arrangement of the plates on the models, although no differences were observed between the groups for the mediolateral peak load. The arrangement of the plates did not have any influence on peak displacement. Similarly, the final value of the mediolateral load was not affected by the arrangement of the plates on the model.Conclusion: The experimental model with 2 separate plates was statistically superior to the model with 2 overlaid plates only in relation to anteroposterior peak load. Despite showing superiority in mediolateral peak load and peak displacement, there was no statistical difference between the groups for these parameters. (C) 2009 American Association of Oral and Maxillofacial Surgeons

Effects of Methylphenidate on performance of a practical pistol shooting task: a quantitative electroencephalography (qEEG) study

Abstract Background The present study examined absolute alpha power using quantitative electroencephalogram (qEEG) in bilateral temporal and parietal cortices in novice soldiers under the influence of methylphenidate (MPH) during the preparatory aiming period in a practical pistol-shooting task. We anticipated higher bi-hemispheric cortical activation in the preparatory period relative to pre-shot baseline in the methylphenidate group when compared with the control group because methylphenidate has been shown to enhance task-related cognitive functions. Methods Twenty healthy, novice soldiers were equally distributed in control (CG; n = 10) and MPH groups 10 mg (MG; n = 10) using a randomized, double blind design. Subjects performed a pistol-shooting task while electroencephalographic activity was acquired. Results We found main effects for group and practice blocks on behavioral measures, and interactions between group and phases on electroencephalographic measures for the electrodes T3, T4, P3 and P4. Regarding the behavioral measures, the MPH group demonstrated significantly poorer in shooting performance when compared with the control and, in addition, significant increases in the scores over practice blocks were found on both groups. In addition, regarding the electroencephalographic data, we observed a significant increase in alpha power over practice blocks, but alpha power was significantly lower for the MPH group when compared with the placebo group. Moreover, we observed a significant decrease in alpha power in electrodes T4 and P4 during PTM. Conclusion Although we found no correlation between behavioral and EEG data, our findings show that MPH did not prevent the learning of the task in healthy subjects. However, during the practice blocks (PBs) it also did not favor the performance when compared with control group performance. It seems that the CNS effects of MPH demanded an initial readjustment period of integrated operations relative to the sensorimotor system. In other words, MPH seems to provoke a period of initial instability due to a possible modulation in neural activity, which can be explained by lower levels of alpha power (i.e., higher cortical activity). However, after the end of the PB1 a new stabilization was established in neural circuits, due to repetition of the task, resulting higher cortical activity during the task. In conclusion, MPH group performance was not initially superior to that of the control group, but eventually exceeded it, albeit without achieving statistical significance.

Double shunt technique for hybrid palliation of hypoplastic left heart syndrome: a case report

We report a technique to palliate hypoplastic left heart syndrome, with no PDA stenting, but with double polytetrafluoroethylene shunt from pulmonary artery to ascending and descending aorta by combined thoracotomies. A 30-day-old female was operated with this technique. Five months after first operation, the child was submitted to Norwood/Glenn operation. Good hemodinamic recovery and initial clinical evolution was observed. The child was extubated in 8th post operatory day and reentubated in the next day due to pulmonary infection. Despite antibiotic treatment, the child died after systemic infectious complications.