Cirugía Ortopédica y Traumatología

¿Disminuyen las complicaciones cutáneas tras la cirugía de fracturas de tobillo con el uso de Aquacel Extra Ag®? Publication date: Available online 22 June 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): M. Luque-Valenzuela, A.J. Sánchez-Aguilera, A. Martín-Vivaldi-Jiménez, R. Jódar-Graus, N. Prados-Olleta Resumen Introducción Las fracturas de tobillo representan un 10% del total de fracturas. La mayor parte requieren tratamiento quirúrgico, que conlleva un importante riesgo de complicaciones de la herida. El objetivo de este estudio ha sido determinar si los apósitos impregnados con plata (Aquacel Ag Extra®) reducen la tasa de complicaciones de la herida quirúrgica tras el tratamiento de las fracturas de tobillo en comparación con el uso de gasas estériles. Métodos De forma prospectiva se han reunido 233 pacientes con fracturas de tobillo subsidiarias de tratamiento quirúrgico. Desde el inicio del estudio en julio de 2017 hasta febrero de 2018, los traumatólogos participantes en el estudio cambiaron el uso de la gasa estéril estándar para cubrir la herida quirúrgica tras su cierre por Aquacel Ag Extra®, manteniendo el resto del protocolo pre- y posquirúrgico igual. Se comparan la tasa de complicaciones cutáneas en ambos grupos, tras un seguimiento de 3 meses. Resultados El análisis estadístico no reflejó diferencias significativas entre ambos grupos. Conclusiones Se necesitan ensayos clínicos aleatorizados para demostrar las ventajas teóricas de los apósitos impregnados con plata y su indicación en Traumatología. Abstract Introduction Ankle fractures account for up to 10% of total fractures. Most of them require surgical fixation, which involves an important risk of wound complications. The aim of this study was to determine whether a silver-impregnated occlusive surgical dressing (Aquacel Ag Extra®) was effective in reducing the rates of wound complications after ankle fracture open reduction and internal fixation compared to standard sterile dressing. Methods We prospectively reviewed 233 patients who underwent ankle fracture open reduction and internal fixation. Surgeons switched from using a standard dressing to an Aquacel Ag Extra® from July 2017 to February 2018, without other major changes in perioperative management. We compared skin complications between both groups after 3 months' follow-up. Results The statistical analysis showed that there is no difference in the prevalence of skin complications between both groups. Conclusions The theoretical advantages of silver impregnated dressings need further prospective randomized controlled studies to assess the appropriate indications for their use in orthopaedic surgery.

Estudio de cohortes comparativo del abordaje Superpath con abordaje convencional posterior en cirugía protésica primaria de cadera no cementada: curva de aprendizaje y resultados a corto plazo Publication date: Available online 17 June 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): J. Más Martínez, J. Sanz-Reig, M. Morales-Santías, D. Bustamante Suarez de Puga, C. Verdu Roman, E. Martinez Gimenez Resumen Antecedentes y objetivo En la actualidad no existe un consenso sobre cuál es el mejor abordaje de cadera para implantar una prótesis. Sin embargo, sí existe una tendencia a reducir al máximo la lesión sobre los tejidos periarticulares, lo cual puede influir en los resultados a corto plazo. El abordaje Superpath permite el acceso a la articulación manteniendo la integridad de los rotadores externos. El objetivo de nuestro estudio fue comparar los resultados a corto plazo del abordaje Superpath con el abordaje convencional posterior. Materiales y métodos Estudio prospectivo de cohorte de 30 pacientes intervenidos mediante abordaje Superpath pareados por sexo, edad, índice de masa corporal y valoración clínica, con 60 pacientes intervenidos mediante abordaje convencional posterior. La valoración clínica se realizó mediante la escala de Harris, Merle d'Aubigné, Womac para el dolor y la función, SF-12 físico y mental, HOS-AVD e IHOT-12. Radiológicamente se determinó el ángulo de inclinación acetabular, alineación del vástago femoral e integración de los implantes. Resultados No hubo diferencias significativas entre ambas cohortes con respecto a las variables preoperatorias. El tiempo quirúrgico, el descenso medio de Hb y Hto y la pérdida sanguínea fue mayor en la cohorte Superpath. La estancia hospitalaria fue similar. Los cuestionarios de valoración clínica mostraron incrementos significativos entre los valores preoperatorios y a los 12 meses en ambas cohortes. El cuestionario IHOT-12 a los 3 meses, el cuestionario SF-12 físico y el cuestionario SF-12 mental a los 12 meses, mostró mayores puntuaciones en la cohorte Superpath, siendo las diferencias significativas. Radiológicamente no se detectaron diferencias entre ambas cohortes. Conclusiones La curva de aprendizaje del abordaje Superpath presenta unos resultados clínicos y radiológicos similares al abordaje posterior durante el primer año tras la prótesis total de cadera. A destacar la necesidad de un mayor tiempo quirúrgico y un mayor sangrado en los pacientes. Abstract Background and objectives There is no current consensus on the most suitable hip approach. However, there is a trend to reduce damage to soft tissue, which may have an influence on early outcomes. The SuperPath approach accesses the capsule maintaining integrity of the external rotators. The purpose of this study was to compare the SuperPath approach with the conventional posterior approach, in terms of early outcomes and radiological results. Material and methods A cohort of 30 patients operated using the SuperPath approach was prospectively matched for age, gender, body mass index and hip function with 60 patients operated using a conventional posterior approach. Clinical evaluation was performed by the Harris score, Merle d'Aubigné score, reduced Western Ontario and McMasters Universities (WOMAC), Short-Form 12 (SF12), IHOT-ADV and IHOT-12 questionnaires. Radiological evaluation was also performed. Results Preoperatively, no significant differences were detected between cohorts. Skin-to-skin operation time and blood loss was higher in the SuperPath cohort. Length of stay was similar between cohorts. Clinical evaluation improved significantly from the preoperative values to the 1-year follow-up. At 3 months the SuperPath cohort showed better results for IHOT-12, and at 12 months for SF. Radiologically, there were no differences between cohorts. Conclusion This prospective randomized study reveals that the learning curve for the SuperPath approach provides similar outcomes to the conventional posterior approach within the first year after surgery. The Superpath approach was associated with longer skin-to-skin operation time, and greater blood loss.

Influencia de la instrumentación sobre el tiempo quirúrgico para implantar una prótesis total de rodilla Publication date: Available online 7 June 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): V.J. León-Muñoz, A.J. Lisón-Almagro, M. López-López Resumen Objetivo Demostrar si existe diferencia en el tiempo que se prolonga la cirugía para implantar una prótesis de rodilla atendiendo al sistema de instrumentación empleado. Material y método Análisis retrospectivo de la duración de 243 intervenciones (tiempo piel-piel y tiempo de isquemia) realizadas por el mismo cirujano. Setenta y dos casos intervenidos con instrumental convencional, 68 asistidos por navegador (computer assisted surgery) y 103 con bloques de corte personalizados (personalized instrumentation system [PSI]). Resultados IC piel-piel 87,85 min (DE 11,86). IC isquemia 94,44 min (DE 11,49). Computer assisted surgery piel-piel 123,46 min (DE 11,27). Computer assisted surgery isquemia 129,63 min (DE 11,37). PSI piel-piel 78,69 min (DE 13,06). PSI isquemia 84,63 (DE 12,06). Existe una diferencia significativa favorable a PSI respecto a los otros sistemas de instrumentación (p 0,000). Conclusiones En nuestro estudio, el consumo de tiempo para la implantación de una prótesis de rodilla ha sido significativamente inferior cuando hemos empleado bloques de corte personalizados, que cuando hemos empleado otros sistemas. Abstract Objective To demonstrate if there is a difference in the time that the surgery is prolonged to implant a knee prosthesis according to the instrumentation system used. Material and methods Retrospective analysis of the duration of 243 interventions (skin-to-skin time and ischemia time) performed by the same surgeon. Seventy-two cases operated with conventional instruments (IC), 68 by means of computer assisted surgery (CAS) and 103 with personalized instrumentation system (PSI). Results IC skin-to-skin time 87,85 min (SD 11,86). IC ischemia time 94,44 min (SD 11,49). Computer assisted surgery skin-to-skin time 123,46 min (SD 11,27). Computer assisted surgery ischemia time 129,63 min (SD 11,37). PSI skin-to-skin time 78,69 min (SD 13,06). PSI ischemia time 84,63 min (SD 12,06). There is a significant difference between PSI and the other instrumentation systems (p 0,000). Conclusions In our study, the time consumption for the implantation of a knee prosthesis has been significantly lower when cutting blocks have been used, than when we have used other systems.

Evolución clínica y presencia de edema óseo subcondral a los dos años de tratamiento con implante de condrocitos autólogos de alta de densidad en la rodilla Publication date: Available online 28 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): J.M. López-Alcorocho, L. Aboli, E. Rodríguez-Iñigo, I. Guillén-Vicente, M. Guillén-Vicente, R. Caballero, M. Casqueiro, T.F. Fernández-Jaen, S. Abelow, P. Guillen-García Resumen Antecedentes y objetivo Recientemente se ha descrito una nueva modalidad de la técnica de implante de condrocitos autólogos sobre membrana de colágeno i/iii llamada HD-ACI (High Density Autologous Chondrocyte Implantation) que está basada en el aumento de la densidad celular. El objetivo de este trabajo fue estudiar la evolución clínica y la incidencia de la aparición de edema óseo en pacientes con lesiones de cartílago en la rodilla tratados con HD-ACI al año y a los 2 años de la intervención. Métodos Se trata de un estudio retrospectivo en 40 pacientes con lesiones condrales grado iii-iv. Todos los pacientes fueron tratados con HD-ACI con una dosis celular de 5 × 106 condrocitos/cm2 de lesión. La percepción subjetiva de la mejora de los síntomas/funcionalidad se valoró mediante la escala del Comité Internacional de Documentación de la Rodilla (IKDC, International Knee Documentation Committee). La presencia de edema óseo se evaluó a los 6, 12 y 24 meses de seguimiento por resonancia magnética. Comité Internacional de Documentación de la Rodilla (IKDC) Resultados Los valores de IKDC mostraron una mejoría significativa a los 12 y 24 meses (p < 0,001). La diferencia media de IKDC entre la visita basal y los 12 meses fue de 26,3 puntos y de 31,6 puntos a los 24 meses. El 27,5% de los pacientes presentaron edema óseo subcondral a los 2 años de seguimiento. Conclusiones HD-ACI es un tratamiento efectivo y seguro que mejora el dolor, la percepción clínica y la funcionalidad de la articulación. No se ha encontrado correlación entre la presencia de edema óseo y la evolución clínica de los pacientes. Abstract Background Recently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type i/iii membrane) based on increasing cell density called HD-ACI (High Density Autologous Chondrocyte Implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1-2 years of follow-up. Methods This is a retrospective study performed with forty patients with chondral injuries grade iii-iv. All patients were treated with HD-ACI with a cellular dose of 5 × 106 chondrocytes /cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. Results IKDC values showed a significant improvement at 12 and 24 months (P < .001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. Conclusions HD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients' clinical outcome.

Tratamiento quirúrgico protocolizado de las tríadas terribles de codo. Resultados y complicaciones Publication date: Available online 22 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): M. Álvarez Muñoz, Juan María Pardo García, L. García Lamas, M. Porras Moreno, V. Jiménez Díaz, D. Cecilia López Resumen Introducción La tríada terrible de codo es una enfermedad asociada a altas tasas de complicaciones, por ello queremos estudiar los resultados y las complicaciones. Material y métodos Se ha utilizado la base de datos de nuestro hospital durante 2005-2015, recogiendo características del paciente, de la fractura, de la cirugía y las complicaciones asociadas, así como resultados funcionales y rango de movilidad. Resultados Se obtuvieron un total de 62 tríadas, de las cuales 27 (43%) eran mujeres y 35 (56%) eran hombres. A todos se les realizó un abordaje lateral de Kaplan y en aquellos que lo necesitaron se complementó con un abordaje medial para reparar el LCM. La cabeza radial se sintetizó en 14 (22%) casos, se colocó una prótesis en 45 (74%) de casos y otras actuaciones en 3 (5%) casos. La osteosíntesis de la apófisis coroides se realizó mediante arpón ± sutura transósea en 41 (62%) pacientes y mediante síntesis en 12 (19%) casos. En 9 (14%) casos no se realizó ninguna actuación. En el 100% de los casos se reparó el LCL y en 9 (14%) hubo que reparar también el LCM. Un 22% de los pacientes precisaron FE por inestabilidad tras la técnica quirúrgica. Respecto a resultados, se obtuvo un rango de movilidad de entre 120°/–20° de flexoextensión y 98°/85° de pronosupinación. En cuanto a complicaciones, obtuvimos un total de 17 (27%). Conclusiones Las tríadas de codo son lesiones osteoligamentosas complejas donde es necesario realizar una cirugía protocolizada, a pesar de lo cual, existen un 27% de complicaciones. Abstract Background Terrible triad of elbow is a complex lesion with a high rate of complications. Our goal is to analyse both clinical results and complications after performing protocolised surgery. Material and methods The database of our hospital was used during 2005-2015, collecting characteristics of the patient, the fracture, the surgery and the associated complications, as well as functional results and range of mobility. Results A total of 62 triads were obtained, of which 27 (43%) were women and 35 (56%) were men. All had a Kaplan lateral approach and those who needed it were complemented with a medial approach to repair the LCM. The radial head was synthesized in 14 (22%) cases, a prosthesis was placed in 45 (74%) cases and other actions in 3 (5%) cases. Osteosynthesis of the choroid process was performed by transosseous harpoon±suture in 41 (62%) patients and by synthesis in 12 (19%) cases. In 9 (14%) cases, no action was taken. In 100% of the cases the LCL was repaired and in 9 (14%) the LCM also had to be repaired. Twenty-two percent of the patients required ESA due to instability after the surgical technique. With respect to results, a range of mobility was obtained between 120°/–20° of flexoextension and 98°/85° of pronosupination. In terms of complications, we obtained a total of 17 (27%). Conclusions Elbow triads are complex lesions where protocolised surgery is necessary, nevertheless the complication rate was 27% in our series.

Lesión del labrum superior anteroposterior (SLAP) en el entorno laboral Publication date: Available online 17 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): F. Navío-Fernández, I. Miranda, E. Sánchez-Alepuz, M. Shahin, E. Pastor-Fernández, V. Carratalá, F.J. Lucas Resumen Antecedentes y objetivo La lesión del labrum superior anteroposterior (SLAP) es una conocida causa de dolor y disfunción del hombro en pacientes activos. El objetivo fue estudiar las lesiones de SLAP en población laboral y valorar la fiabilidad de la exploración física y las técnicas de imagen en el diagnóstico de las lesiones de SLAP en el entorno laboral. Material y métodos Revisión retrospectiva de 58 lesiones de SLAP tratadas en nuestra mutua laboral desde 2005 hasta 2015 en 815 pacientes en los que se realizó una artroscopia de hombro. Se han recogido datos del mecanismo lesional, datos clínicos, pruebas complementarias (comparando el informe radiológico inicial con el de un radiólogo especializado en musculoesquelético), hallazgos artroscópicos y tratamiento realizado. Resultados El mecanismo lesional más frecuente ha sido la lesión aguda levantando peso, en la mayoría de casos, por encima de la cabeza. La lesión de SLAP se sospechó en el 41% con anamnesis y exploración física, en el 29% de los informes radiológicos iniciales y en el 52% en los informes del radiólogo especialista en musculoesquelético. Presentaron lesiones asociadas el 78%, la mayoría lesiones del manguito rotador. Conclusión La lesión de SLAP en el entorno laboral es infrecuente y muchas veces se diagnostica durante una artroscopia realizada por otra lesión. La artrorresonancia magnética y la resonancia magnética tienen menos fiabilidad que la evaluación clínica para su diagnóstico. Un radiólogo especializado en musculoesquelético podría mejorar la rentabilidad de las pruebas de imagen en el diagnóstico de estas lesiones. Abstract Background and objective Superior labral anterior to posterior (SLAP) injuries are widely recognised as a cause of pain and dysfunction in the shoulders of active patients. The aims of the present study were to analyze SLAP injuries in the workplace, and to evaluate the reliability of physical examination and imaging techniques for the diagnosis of work-related SLAP injuries. Material and methods Retrospective chart review of 58 SLAP injuries treated in our occupational health centre from 2005 to 2015 in 815 patients undergoing shoulder arthroscopy. Data were collected on mechanism of injury, clinical proceedings, complementary tests (contrasting the initial magnetic resonance imaging report with that of a radiologist specializing in musculoskeletal pathology), arthroscopy findings and treatments performed. Results The most common mechanism of injury was acute injury while handling weight, in the majority of cases, above the head. SLAP injury was suspected in 41% of cases through anamnesis and physical exam, in 29% through the initial magnetic resonance imaging report, and in 52% through the specialised radiologist's report. In 78%, associated injuries were present, the most common being rotator cuff injuries. Conclusions SLAP injuries in the workplace are rare and are often a diagnostic finding during surgical intervention performed for a different associated injury. Arthro-magnetic resonance imaging and magnetic resonance imaging have lower reliability than physical exams in the diagnosis of work-related SLAP injuries. A radiologist specializing in musculoskeletal pathology could probably improve the reliability of imaging test interpretation in work-related SLAP injuries.

Fracturas de astrágalo. Resultados funcionales en pacientes politraumatizados Publication date: Available online 8 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): F.J. Hierro-Cañas, P. Andrés-Cano, G. Rabadán-Márquez, M.A. Giráldez-Sánchez, P. Cano-Luis Resumen Las fracturas de astrágalo son lesiones poco frecuentes (0,1-0,9%) y con un alto índice de complicaciones. Una de las situaciones en las que puede darse una fractura de astrágalo es en el contexto de un politraumatismo, lo que puede comprometer aún más el pronóstico funcional. El objetivo del presente trabajo ha sido analizar los resultados funcionales en los pacientes con fracturas de astrágalo según se produjeran en el contexto de un politraumatismo o no. Estudio observacional sobre una cohorte retrospectiva de 24 pacientes intervenidos por fractura de astrágalo en nuestro centro (2008-2016). Se agruparon según fuesen politraumatizados (ISS > 16) o no (ISS ≤ 16). Revisión de variables sociodemográficas, radiográficas, funcionales (escala EVA de dolor y FADI –Foot and Ankle Disability Index–) y la aparición de complicaciones como artrosis o necrosis avascular. Revisión de 25 fracturas de astrágalo en 24 pacientes con una edad media de 38 años (19-75) y un seguimiento medio de 4,2 años (0,5-9). Según el ISS un 44% de pacientes (11) fueron politraumatizados y un 56% (14) no. Respecto a los resultados funcionales entre politraumatizados y no politraumatizados, la puntuación media según la escala FADI fue de 62 puntos y de 76,9 respectivamente y según la escala EVA fue de 5,8 y 4,3 puntos respectivamente. Respecto a las complicaciones, en el grupo de politraumatizados se presentaron en un 64% de los pacientes y en los no politraumatizados en un 43%. Un 36% de los pacientes politraumatizados tuvieron signos clínicos y radiológicos de artrosis subastragalina y un 27% fueron intervenidos mediante una artrodesis frente al 35% y al 27% del grupo de no politraumatizados, Respecto a la necrosis avascular del astrágalo, se registro un 27% frente a un 0% de los no politraumatizados. Abstract Talar fractures are uncommon lesions (0.1-0.9%) and have a high rate of complications. One of the situations in which a fracture of the talus can occur is in the context of polytrauma which may further compromise the functional prognosis. The aim of this study was to analyze the functional results in patients with talar fractures whether or not they occurred in the context of polytrauma. Observational study on a retrospective cohort of 24 patients operated in our centre (2008-2016). They were grouped according to whether they were polytraumatized (ISS > 16) or not (ISS ≤ 16). Review of sociodemographic, radiographic, functional variables (VAS pain scale and FADI –Foot and Ankle Disability Index–) and the onset of complications such as arthrosis, arthrodesis or avascular necrosis. Review of 25 talar fractures in 24 patients with a mean age of 38 years (19-75) and a mean follow-up of 4.2 years (0.5-9). According to the ISS, 44% of patients (11) were polytraumatized and 56% (14) were not. The average score according to the FADI scale was 62 points for the polytraumatized patients and 76.9 for the non-polytraumatized patients. The pain according to the VAS scale was 5.8 points in the group of polytraumatized patients and 4.3 in the non-polytraumatized patient group. Regarding complications, 64% of the polytraumatized patients and 43% of the non-traumatized patients had a complication. 36% of the polytraumatized patients had clinical and radiological signs of subtalar arthrosis compared to 35% of the non-traumatized patients, of whom 27% underwent arthrodesis compared to 28% of the non-traumatized patients. 27% of the polytraumatized patients were diagnosed with avascular necrosis as opposed to 0% of the non-polytraumatized patients.

Estudio antropométrico de la glena humana en una población española normal Publication date: Available online 8 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): L. Rosales-Rosales, A.P. Rosales-Varo, M.A. García-Espona, O. Roda-Murillo, I. Montesinos, P. Hernandez-Cortés Resumen Objetivo El objetivo de este estudio es evaluar el tamaño de la glena en una población española normal, compararla con resultados previos en otras poblaciones y relacionarlo con los tamaños de implante que se comercializan para la artroplastia invertida de hombro. Material y métodos Estudio antropométrico de la glena humana utilizando tomografías computarizadas de 154 pacientes con edades superiores a 30 años, realizados entre enero de 2015 y diciembre de 2017. Se valoran tomografías computarizadas de hombro con cortes de 2 mm de grosor y 0 mm de intervalo entre cortes, en algoritmo óseo y de partes blandas, realizándose reconstrucción 3 D sobre la cual se obtienen mediciones de longitud y anchura de la glena. El punto superior de la glena se determinó en la zona superior del ovoide de la glena, en el tubérculo supraglenoideo, justo por debajo del reborde circunferencial que rodea la glena. El punto inferior se determinó como el punto más alejado del punto superior en el contorno de la glena, a nivel superior del reborde circunferencial que rodea la glena. Los puntos anterior y posterior fueron determinados como los extremos del eje transversal mayor en un plano perpendicular al eje superoinferior, por dentro del reborde circunferencial que rodea la glena. Las diferencias entre sexos, edad, altura, peso y relaciones de tamaños fueron evaluados. Resultados La glena tiene un eje longitudinal medio de 28,78 mm y una anchura de 20,27 mm. Los valores del tamaño de la glena son significativamente diferentes en hombres y mujeres, siendo mayor en hombres. El tamaño de la glena está bien correlacionado con la estatura del paciente, existiendo una asociación positiva entre la estatura y la longitud y anchura de la superficie glenoidea. Las metaglenas circulares disponibles hoy en el mercado presentan tamaños no inferiores a 24-25 mm de diámetro. Conclusión La población del sur de España presenta un tamaño de la superficie glenoidea inferior a la población americana y semejante a la cohorte asiática. Los datos antropométricos expresados pueden ser útiles para la elección de la metaglena más apropiada en la población del sur de España. Abstract Objective To evaluate the size of the glenoid in a southern Spanish population, to compare it with previous results from other populations and determine the size of the implants that are marketed for shoulder arthroplasty. Material and methods Between January 2015 and December 2017, an anthropometrical study of the human glenoid was performed using computed axial tomography scans (CT) of 154 patients over 30 years old. The glenoid dimensions were analysed 3-dimensionally using 2 mm interval thicknesses, determining the average height and width of the glenoid. The upper point of the glenoid geometry was determined as the supraglenoid tubercle of the ovoid glenoid surface, where the long head of the biceps tendon is thought to originate. The lower point was then positioned at the furthest point from the upper point on the glenoid contour. Anterior and posterior points were determined such that the 3-dimensional anterior-posterior distance was maximized on the plane perpendicular to the upper-lower axis. Sex differences and correlations between sides and among the respective parameters in the glenohumeral dimensions were also evaluated. Results The glenoid had an average height of 28.78 mm and width of 20.27 mm. The values were significantly different between the men and the women, being greater in the men. The glenoid size is well correlated with the patient's size. Direct correlations exist between the glenoid height and width and the glenoid size and the patient's height. The available metaglenoids currently on the market are no bigger than 25-24 mm. Conclusion In comparison, the southern Spanish population have a glenoid size similar to the Caucasian population, but smaller than that of the American population. The data shown could be useful to improve the design of shoulder prostheses for the southern Spanish population.

Determinantes sociodemográficos de la comprensión de la información clínica en pacientes hospitalizados intervenidos de cirugía traumatológica Publication date: Available online 7 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): E.M. García-García, B. Sánchez-Sabater, I. Medrano-Morte, A. Luna-Maldonado Resumen Introducción El proceso de la información clínica es el pilar de la relación médico-paciente; comienza con la información proporcionada antes de la firma del consentimiento informado y finaliza al terminar la relación médico-enfermo. La influencia de las variables demográficas en el proceso de información ha sido poco estudiada en el paciente hospitalizado intervenido quirúrgicamente. En este estudio respondemos a dos cuestiones: 1) ¿Influye el género en el proceso de información en estos pacientes? 2) ¿Existen otros factores que influyan en el mismo? Método Estudio prospectivo realizado a través de un cuestionario diseñado «ad hoc» en una muestra de 200 pacientes ingresados tras la realización de una intervención quirúrgica en el servicio de Cirugía Ortopédica y Traumatología en nuestro hospital. El muestreo se ha realizado de manera aleatoria simple. Resultados Hemos hallado diferencias en la concordancia de las respuestas por género en la pregunta sobre el tipo de prioridad de la cirugía, siendo la mujer la que mejor lo conoce (p = 0,04). El resto de preguntas no muestran diferencias por género. Sin embargo, en la población analizada, son la edad y el nivel de estudios los principales factores modificadores de la comprensión, y ambos están relacionados con el género (p < 0,0001; p = 0,003, respectivamente). Conclusiones En la práctica clínica es importante tener presente aquellos factores que influyen en el proceso de información. Según nuestros resultados, los factores que definen una mayor vulnerabilidad con relación al proceso de información son la edad y el bajo nivel de estudios. Abstract Introduction The clinical information process is the basis of the doctor-patient relationship. It starts with the information provided before signing informed consent and ends on the termination of the doctor-patient relationship. The influence of demographic variables in the information process has not been thoroughly studied for inpatients undergoing surgery. In this study we aim to answer two questions: 1) Does gender have an influence on the information process for these patients? 2) Are there other factors that affect the process? Method A prospective study carried out using an 'ad hoc' designed survey on a 200-inpatient sample after undergoing surgery in the trauma and orthopaedics department of our hospital. Sampling was simple random. Results We found differences in the consistency of the answers by gender in the question regarding surgical priority, with the women having a better understanding of it (p = .04). The rest of the questions show no differences by gender. However, in the population analyzed, age and educational level are the main modifiers of understanding, and they are both related to gender (p < .0001; p = .003, respectively). Conclusions In clinical practice, it is fundamental to keep in mind the factors that affect the information process. According to our results, the factors that define greater vulnerability in relation to the information process are age and low educational level.

Carcinoma de células de Merkel de localización y presentación atípica Publication date: Available online 6 May 2019 Source: Revista Española de Cirugía Ortopédica y Traumatología Author(s): R. Fernández-Regueiro, F.J. Suárez-Sánchez, J. Morís-de la-Tassa Resumen El tumor de células de Merkel es un tumor cutáneo raro, de elevada malignidad, mal pronóstico y baja supervivencia. Se caracteriza por su tendencia a la invasión ganglionar y vascular, y por un alto porcentaje de recurrencia locorregional en el año siguiente a la extirpación quirúrgica. Afecta a adultos entre los 60 y 80 años, y se localiza preferentemente en cabeza y cuello. Presentamos el caso de un varón de 85 años que acude por masa glútea ulcerada de 4 meses de evolución. El diagnóstico se realizó por estudio histopatológico e inmunohistoquímico. Un diagnóstico precoz y un tratamiento adecuado son importantes para mejorar el pronóstico de estos enfermos. Abstract Merkel cell tumour is a rare skin tumour of high malignancy, poor prognosis and low survival. It is characterized by its tendency to lymph node and vascular invasion and by a high percentage of locoregional recurrence in the year following surgical removal. It affects adults between 60 and 80 years of age and often occurs in the head and neck. We present the case of an 85-year-old man presenting with an ulcerated gluteal mass of 4 months' evolution. Diagnosis was by histopathological and immunohistochemical study. Early diagnosis and appropriate treatment are important to improve the prognosis of these patients.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Acupuncture and Tuina Science

Effect of electroacupuncture on NF-κB and NLRP3 inflammasome in uterine tissues of rats with primary dysmenorrhea Abstract Objective To observe the effect of electroacupuncture (EA) on nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in uterine tissues of rats with primary dysmenorrhea (PD), thus to explore the possible mechanism of EA for PD. Methods Fifty female Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, an EA at non-acupoint group, an EA at acupoint group and a Western medicine group, with 10 rats in each group. Except for the normal group, rats in the other four groups were treated with estradiol benzoate combined with oxytocin for 11 d to establish PD rat models. From day 1 of the modeling, rats in the normal group and the model group were only properly grasped without any intervention; Guanyuan (CV 4) and Sanyinjiao (SP 6) were selected for EA treatment in the EA at acupoint group; rats in the EA at non-acupoint group were treated with EA at 5 mm away from the acupoints selected above; rats in the Western medicine group were treated with ibuprofen via gavage. Rats in each group were treated for 10-day successively. On the 11th day, except for the normal group, rats in the other groups were intraperitoneally injected with oxytocin (2 U/rat), and the writhing number within 30 min in each group was compared; the pathological changes in rat uteruses were observed by hematoxylin-eosin (HE) staining, and the pathological damage scores were evaluated. Protein expression levels of NF-κB p65, phospho-NF-κB p65, NLRP3, cysteine aspastic acid-specific protease 1 (caspase-1), interleukin (IL)-1β and IL-18 were detected by Western blot. Results Compared with the normal group, the writhing number increased significantly (P<0.05), and the extensive exfoliation of the endometrium, severe edema, and histopathological score all increased significantly in the model group (P<0.05) as well as the protein levels of NLRP3, caspase-1, IL-1β and IL-18, and the ratio of phospho-NF-κB p65/NF-κB p65 in rat uterine tissues (all P<0.05); compared with the model group, the numbers of writhing reaction decreased within 30 min (P<0.05), the endometrial exfoliation was rare, the edema degree was mild, and the histopathological scores decreased significantly (all P<0.05) in the EA at acupoint group and the Western medicine group; compared with the model group, the phospho-NF-κB p65/NF-κB p65 ratio and the NLRP3, caspase-1, IL-1β and IL-18 protein levels of rat uterine tissues in the EA at acupoint group were significantly lower (P<0.05); compared with the model group, the caspase-1, IL-1β and IL-18 protein levels of the rat uterine tissues decreased significantly (all P<0.05), and the differences in the NLRP3 and phospho-NF-κB p65/NF-κB p65 levels were statistically insignificant (all P>0.05) in the Western medicine group; compared with the Western medicine group, the phospho-NF-κB p65/NF-κB p65 ratio, also the NLRP3, IL-1β and IL-18 protein levels of the uterine tissues decreased significantly in the EA at acupoint group (all P>0.05), while the difference in the caspase-1 level was statistically insignificant (P>0.05); there were no significant differences between the EA at non-acupoint group and the model group in any indicators(P>0.05). Conclusion EA at acupoints significantly improves the pain and pathological damages of PD rats. The mechanism may be related to the reduced uterine inflammation via inhibiting NF-κB phosphorylation and NLRP3 activation in uteruses of PD rats.

Research advances in neurobiological mechanism of acupuncture for amblyopia Abstract Amblyopia greatly affects the physical and mental development of children. Acupuncture is effective for amblyopia, though its mechanism remains unclear. This article summarized the mechanism of acupuncture treatment of amblyopia from the perspectives of morphology of neurons in visual cortex, visual electrophysiology, and molecular biology, etc. It was found that acupuncture may treat amblyopia through repairing the morphological and ultrastructural damages of neurons in visual cortex, promoting the electrical activities in visual pathway and visual cortical neurons, and modulating the synthesis and expression levels of factors involved in visual system. Nevertheless, further studies are required to unveil the mechanism of acupuncture treatment of amblyopia.

Analysis of clinical literature on acupuncture-moxibustion for dyspepsia based on data mining Abstract Objective To summarize the point selection pattern and treatment method in acupuncture-moxibustion for dyspepsia through data mining of the related clinical literatures in recent two decades, and to provide reference for clinical application. Methods With data mining technology, clinical literatures related to acupuncture-moxibustion for dyspepsia published between January 1997 and July 2018 were collected from major Chinese databases, and the treatment methods, point and meridian frequencies were summarized and analyzed. Results A total of 106 studies were included. For meridians, the top 5 meridians used were the Stomach Meridian, Conception Vessel, Spleen Meridian, Liver Meridian and Pericardium Meridian. For point selection, the leading 5 points were Zusanli (ST 36), Zhongwan (CV 12), Shangwan (CV 13), Xiawan (CV 10) and Sanyinjiao (SP 6). For major and adjunct points, the 5 most significant major points were Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6), Sanyinjiao (SP 6) and Shangwan (CV 13); the 5 most significant adjunct points were Neiting (ST 44), Qihai (CV 6), Fenglong (ST 40), Yinlingquan (SP 9) and Tianshu (ST 25). For treatment method, the top 3 methods used were moxibustion alone, acupuncture alone and acupuncture combined with medicinal herbs. Conclusion The main meridian chosen in acupuncture-moxibustion for dyspepsia was the Stomach Meridian, and the points were mainly selected from the Stomach Meridian; treatment method was moxibustion alone, which may provide reference for clinical treatment of this disease.

Treatment of neck type cervical spondylopathy with Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method: a randomized controlled trial Abstract Objective To observe the clinical effect of Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method versus ordinary acupuncture on superficial fascia for treating neck type cervical spondylopathy in Kyrgyz. Methods A total of 64 Kyrgyz patients conforming to the diagnostic criteria of neck type cervical spondylopathy were included. The patients were randomized into a Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture group and a conventional acupuncture group, with 32 cases in each group. Patients in the Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture group were treated with Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method to stimulate the superficial fascia, the stimulation sites were primarily located at bilateral sides of the cervical vertebra as well as the trigger points in shoulder-neck region; patients in the conventional acupuncture group were punctured at the same acupoints, with twirling reducing method, and the depth of insertion was determined by the treated region. Patients in both groups received treatment every day for a succession of 5 d as a course, with a 2-day interval between 2 courses, and the whole treatment lasted for 3 courses. After 3 courses of treatment, the McGill pain questionnaire (MPQ) and neck disability index (NDI) were measured to compare the clinical effect between the two groups. Results After treatment, scores of MPQ and NDI scale dropped when compared with those before treatment, and the differences showed statistical significance (all P<0.05); scores of MPQ and NDI in the Jin Gou Diao Yu (gold-hook-fishing) acupuncture group were substantially lower than those in the conventional acupuncture group, and the differences showed statistical significance (all P<0.05). The total effective rate was 96.9% in the Jin Gou Diao Yu (gold-hook-fishing) acupuncture group and the cured rate was 78.1%, which were higher than 81.3% and 40.6% in the conventional acupuncture group, and the differences showed statistical significance (all P<0.05). Conclusion Zheng's Jin Gou Diao Yu (gold-hook-fishing) acupuncture method by stimulating superficial fascia to treat cervical spondylopathy in Kyrgyz can produce a better clinical effect than conventional acupuncture treatment, and is effective in improving pain and stiffness in patients, and thus is worth clinical popularization.

Review on the development and application of electroacupuncture apparatus in the past 5 years in China Abstract Objective To review the problems existing in the development and application of current electroacupuncture (EA) apparatuses, and provide reference for the development of EA apparatuses. Methods Related literatures about EA apparatus were derived from China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang) and Chongqing VIP Database (CQVIP) between 2013 and 2017. Literatures about the development of EA apparatuses and the application for experimental research and clinical treatment published in Chinese journals were retrieved, and the development and application of EA apparatuses were summarized. Results Among the 107 selected literatures, 48 types of EA apparatuses were used, of which only 11 models could be found in the registration list and within the validity period. There was no registration information for the EA apparatus newly developed in the past 5 years. The EA parameters used in experimental research and clinical treatment in Chinese medicine were different, and the combination of stimulation parameters was diverse. Conclusion At present, most of the new EA products are still in the experimental or research stage, and the transformation of results has not yet been achieved. Moreover, there is no unified standard for the use of EA apparatus and its stimulation parameters in experimental research and clinical treatment, which is not conducive to the standardization process of EA stimulation.

Effect of moxibustion on VEGF and EGF expressions in tumor tissues of rats with gastric tumor Abstract Objective To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05); compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (both P<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (both P<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (both P<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05); compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (both P<0.05). Conclusion Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.

Efficacy observation on pediatric tuina plus Chinese medicine for exogenous fever in children Abstract Objective To observe the clinical effects of pediatric tuina plus Chinese medicine for exogenous fever in children. Methods A total of 150 children with exogenous fever were randomly divided based on the random digital table into a control group (75 cases) and a treatment group (75 cases). The control group was treated with oral Xiao'er Chaigui Tuire Keli (<1 year old, 0.5 bag/time; 1–3 years old, 1 bag/time; 4–6 years old, 1.5 bags/time), 4 times/day. The treatment group was treated with pediatric tuina plus the intervention of the control group. The amount and usage of Chinese medicine were the same as those of the control group; tuina was conducted 1 time/day. The clinical effects and adverse reactions were observed after 3 d of treatment in both groups. The recurrence was observed within 7 d after the end of treatment. Results The total effective rate was 92.0% in the treatment group and 81.3% in the control group. The difference between the two groups was statistically significant (P<0.05). There were no obvious adverse reactions in the two groups after treatment. The recurrence rate was 1.5% in the treatment group and 13.1% in the control group. The difference in the recurrence rate between the two groups was statistically significant (P<0.05). Conclusion Pediatric tuina plus Chinese medicine is effective in treating children with exogenous fever.

Study on the angle of needling Yamen (GV 15) in atlanto-axial dislocation patients Abstract Objective To compare the risk angle and safety angle of needling Yamen (GV 15) between the atlanto-axial dislocation (AAD) patients and healthy subjects. Methods A total of 177 AAD patients diagnosed and treated at the Center of Upper Cervical Vertebra of Beijing China-Japan Friendship Hospital between January 2010 and January 2018 were included in the AAD group. Another 207 healthy subjects were included in the normal group. There were totally 191 males and 193 females. The MRI scan was performed for the cervical vertebrae to measure the risk angle and safety angle of acupuncture at Yamen (GV 15) on the sagittal image. Results In the AAD group, the risk angle was (13.14±3.99)° and the relative safety angle was (10.31±3.23)° for the perpendicular needling, while the oblique needling risk angle was (9.09±3.09)° for the male; the risk angle was (12.12±2.74)° and the relative safety angle was (10.56±2.09)° for the perpendicular needling, while the oblique needling risk angle was (9.70±2.95)° for the female. In the normal group, the risk angle was (7.89±1.59)° and the relative safety angle was (10.21±3.55)° for the perpendicular needling, while the oblique needling risk angle was (16.07±1.77)° for the male; the risk angle was (6.93±1.45)° and the relative safety angle was (10.70±2.94)° for the perpendicular needling, while the oblique needling risk angle was (14.89±2.18)° for the female. The perpendicular needling risk angles for the males and females in the AAD group were larger than those in the normal group, and the differences were statistically significant (both P<0.01); for the inner-group comparison, there was no significant difference in the perpendicular needling risk angle between the male and the female in the AAD group (P>0.05); however, the perpendicular needling risk angle for the male was larger than the female, and the difference was statistically significant in the normal group (P<0.01). There were no significant differences in the relative safety angle for both the male and the female between the AAD group and the normal group (both P>0.05). For the inner-group comparison, there was no significant difference in the relative safety angle between the male and the female (P>0.05). The oblique needling risk angles for both the males and females were smaller in the AAD group than those in the normal group, and the differences were statistically significant (both P<0.01); the oblique needling risk angle for the male was not significantly different from that for the female in the AAD group (P>0.05); in the normal group, the oblique needling risk angle for the male was larger than that for the female, and the difference was statistically significant (P<0.01). Conclusion Under the AAD condition, the risk angle and safety angle of acupuncture at Yamen (GV 15) change significantly, perpendicular needling should be better if performed slightly lower than the horizontal direction, and the oblique needling should be safer across the occipital foramen toward the occipital bone.

Efficacy and safety of electroacupuncture for perimenopausal insomnia: a randomized controlled trial Abstract Objective To observe the effectiveness and safety of electroacupuncture (EA) plus Luohua Anshen oral liquid for patients with perimenopausal insomnia. Methods A total of 66 participants who met the inclusion criteria were enrolled in the randomized controlled trial and allocated to a treatment group and a control group at a ratio of 1:1, with 33 cases in each group. Both groups were given Luohua Anshen oral liquid as a basic treatment. The treatment group was additionally given EA every other day, three times a week. Both groups were treated for four weeks and a four-week follow-up was conducted. The scores of Pittsburgh sleep quality index (PSQI), Kupperman index (KI) and traditional Chinese medicine sleep syndrome scale (TCMSSS) were recorded at pre- and post-treatment, and at the follow-up. Meanwhile, adverse effects were monitored and recorded. Results After four-week treatment, the global scores of PSQI, KI and TCMSSS in both groups declined significantly (all P<0.05), and the decreases in the treatment group were more significant than those in the control group (all P<0.05). The global scores of PSQI, KI and TCMSSS in both groups at the follow-up visit were significantly different from the corresponding baseline (all P<0.05), while insignificantly different from those assessed at post-treatment (all P>0.05). The total effective rate was 93.9% in the treatment group, significantly higher than 72.2% in the control group (P<0.05). No significant adverse event was reported in this trial excepted one patient experienced slight dizziness in the first acupuncture treatment. Conclusion EA plus Luohua Anshen oral liquid is safe for perimenopausal insomnia with satisfactory short- and long-term effectiveness, and it shows certain advantage compared with using Luohua Anshen oral liquid alone.

Efficacy comparison of different forms of dog-days acupoint application for prevention and treatment of chronic bronchitis Abstract Objective To analyze the clinical effect of traditional dog-days acupoint application and Magic Acupuncture Patch (Manji) in the prevention and treatment of chronic bronchitis (CB) in remission stage in the past five years, and explore the principle of action and effective stimulation, to provide the evidence for treating CB by acupoint application. Methods A retrospective study was conducted on 405 patients with CB who met the inclusion criteria. All patients were treated with dog-days acupoint application or Magic Acupuncture Patch between 2013 and 2017. The clinical data of 405 patients were statistically analyzed to compare the prevention and treatment effects of dog-days acupoint application and Magic Acupuncture Patch, and different degrees of stimulation of dog-days acupoint application. Results Among the dog-days acupoint application groups, the total effective rate was 63.6% in the light stimulation group, 93.1% in the moderate stimulation group, and 94.8% in the strong stimulation group. The differences in the total effective rate between the light stimulation group and the moderate stimulation group, as well as the strong stimulation group, were statistically significant (both P<0.05). There was no significant difference in the total effective rate between the moderate stimulation group and the strong stimulation group (P>0.05). The total effective rate was 83.9% in the dog-days acupoint application group, versus 45.4% in the Magic Acupuncture Patch group, and there was a statistically significant difference between the two groups (P<0.05). Conclusion The efficacy of dog-days acupoint application in the prevention and treatment of CB is better than that of Magic Acupuncture Patch; the degree of stimulation is the basis for the effect of dog-days acupoint application on prevention and treatment of CB, and the moderate and strong stimulations are more appropriate.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicinal Chemistry Research

Preparation and biological evaluation of quinoline amines as anticancer agents and its molecular docking Abstract A series of 2-chloro N-substituted amino quinolines (2a–2j) were prepared and characterized by analytical and spectroscopic methods. As quinoline is an important pharmacophoric moiety, the prepared compounds were screened against a non-small cell lung cancer cell line, A549. One of the compounds, 2-chloro-8-methyl-N-(quinolin-5-yl)quinolin-4-amine (2b) is found to be active with inhibition concentration value of (IC50) 29.4 μM. The molecular docking studies with the predominant PI3K/AKT/mTOR pathway proteins also revealed the lesser binding energy with 2b. All the compounds are predicted to satisfy the ADME profile and the results let us to consider 2b as a lead compound for new generation of A549 cell line inhibitors and for further studies in this way.

Green synthesis and 3D pharmacophore study of pyrimidine and glucoside derivatives with in vitro potential anticancer and antioxidant activities Abstract A facile and an efficient one-pot green synthesis of pyrimidine derivatives using the environmentally friendly Cerium(IV) ammonium nitrate (CAN) as catalyst and water as a solvent has been described. Some of the synthesized pyrimidines react with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide in ethanol containing potassium hydroxide to give S-glucoside derivatives. The structures of the newly synthesized compounds were elucidated on the basis of their spectral and elemental analyses. In addition, selected derivatives of the products were screened for their anticancer activities against four tumor cell lines using MTT assay and the results showed that some of these compounds have potent cytotoxic effect, as concluded from their IC50 values. Molecular modeling studies including generation of a 3D pharmacophore model were carried out. The study showed high correlation with the experimental results. Antioxidant activity of the synthesized products was also investigated and most of them showed potent activity.

In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus Abstract Ten 5-functionalized derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile were synthesized and their antiviral activities against the human cytomegalovirus (HCMV) were evaluated in vitro. Bioassays showed that seven compounds exhibited considerably higher antiviral activity (EC50: < 0.05 μM) against a normal laboratory HCMV strain (AD-169) in human foreskin fibroblast cells than Ganciclovir (EC50 = 0.32 μM), an anti-HCMV agent in clinical use. Additionally, the HCMV-resistant isolate (GDGr K17) was tested for sensitivity to 1,3-oxazole derivatives with most antiviral potency against the strain AD169. A one of them (5-((2-hydroxyethyl)(methyl)amino)-2-(4-methylphenyl)-1,3-oxazole-4-carbonitrile) showed very high potency (EC50: < 0.05; CC50: >150 µM, and SI50 = 3125) towards the resistant isolate compared to standard drugs Cidofovir (EC50 = 0.10 µM, CC50: >30 µM and SI50: <4). But, in contrast to the primary assays, the antiviral activity of these compounds against both the normal strain and the resistant isolate of HCMV were considerably less than one of Cidofovir in secondary assay. These results provided evidence that derivatives of 1,3-oxazole could be useful for developing new anti-HCMV drugs.

New fluoroquinolones/nitric oxide donor hybrids: design, synthesis and antitubercular activity Abstract New nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds 2b, 3a, 4a, 5a, and 2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulation in mycobacteria. The additional growth inhibition effect that is distinct from gyrase poisoning may be due to release of NO or enhancement of lipophilicity. These data are augmented by docking results where the docked compounds did not exert additional significant bindings over the parent fluoroquinolones.

3D-QSAR, molecular docking, and new compound design of pyrimidine derivatives as Src small molecule inhibitors Abstract Non-receptor tyromethod, The sine kinase Src is one of the important molecular targets for potential triple-negative breast cancer (TNBC). In this study, the structure and acitivity relationship of 51 Src small molecule inhibitors with potential pyrimidine derivatives was explored. On the basis of ligand composite, the relationsConducted a phase hip between molecular structure and inhibitory activity of MDA-MB-231/435 TNBC cell lines was studied by using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis fields (CoMSIA), and Topomer CoMFA (T-COMFA) methods, and thereby two sets of three-dimensional quantitative structure–activity relationship models were established to analyze the molecular structure and anti-TNBC activity. The results indicated that the q2 of CoMFA, CoMSIA, and Topomer CoMFA models was 0.698/0.719, 0.73/0.684, 0.674/0.683, and r2 was 0.994/0.991, 0.991/0.985, 0.946/0.959, respectively. Moreover, the three-dimensional equipotential map also revealed the relationship between structural characteristics and inhibitory activity, and molecular docking was investigated by Surflex-dock. The data proved that this model had good predictive ability and can further guide the design and modification of 3- (phenylethynyl) −1 hydropyrazolyl [3anilo-d] pyrimidine-4-amine derivatives inhibitors. According to the three-dimensional quantitative structure–activity relationship model of two TNBC cell lines of MDA-MB-231/435, 13 and 11 compounds were designed respectively, and the predicted activity values showed effective inhibition of SRC.

Synthesis and in vitro evaluation of substituted tetrahydroquinoline-isoxazole hybrids as anticancer agents Abstract A series of isoxazole linked to 4-(2-oxopyrrolinidyl-1)-tetrahydroquinoline derivatives was efficiently synthesized. The synthetic route started with the formation of the corresponding N-propargyl tetrahydroquinoline derivatives via cationic Povarov reaction. Tetrahydroquinoline-isoxazole hybrid systems (3a–p) were obtained with good yields (42–88%) through a 1,3-dipolar cycloaddition reaction with a click chemistry approach. These compounds have been tested for their in vitro cytotoxic activity against four different human cancer cell lines, lung (A549), liver (HepG2), and melanoma murine (B16F10) using the conventional MTT assay. Among all tetrahydroquinoline-isoxazole hybrids synthesized, compounds 3a, 3e, 3j, and 3m showed promising in vitro activity against HepG2 cancer cell line with considerable selectivity. Compounds 3a (IC50 = 6.80 µM, SI = 14.7) and 3j (IC50 = 5.20 µM, SI > 16.1) exhibited the highest cytotoxic effect. The death pathway related to cytotoxicity of the compound 3j showed necrotic characteristics selectively on the tumor cell line, also showed an improved in vitro activity against the tested reference drug (oxaliplatin), without significant affectation on the viability of hepatocytes. In general, results suggested that these type of hybrid compounds might have therapeutic potential in future investigations on hepatocellular carcinoma.

Pyrazole–chalcone derivatives as selective COX-2 inhibitors: design, virtual screening, and in vitro analysis Abstract In the process of research and development of new drugs, in silico analyzes are widely used. They address the pharmacokinetics of the molecules in study and can predict the binding mode and affinity, using a docking software. This approach can optimize the development of new drugs, reducing costs, time, and resources. In this study, a library of 300 pyrazole–chalcone derivatives were designed, the in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were evaluated, and a structure-based virtual screening was performed using AutoDock Vina. The docking results exhibited that the derivatives binding mode at the COX-2 active site is similar to celecoxib, the reference drug, and presented similar binding energy. Six compounds were synthetized and tested for in vitro inhibition of the COX-1 and COX-2 isoenzymes and the selectivity index (SI) was calculated. The compound 2a11 showed the best activity for COX-2 (IC50COX-2 = 0.73 μM) whereas the control, celecoxib, resulted IC50COX-2 = 0.88 μM. All the other compounds synthetized presented better potency for COX-2 inhibition than the control. Compound 2a23 exhibited the higher SI, of 280.17 (IC50COX-1 = 210.13 μM/ IC50COX-2 = 0.75 μM), while celecoxib was 246.88 (IC50COX-1 = 217.26 μM/ IC50COX-2 = 0.88 μM). These results corroborate with a possible anti-inflammatory activity and COX-2 selectivity of the new compounds synthetized.

Natural thiopeptides as a privileged scaffold for drug discovery and therapeutic development Abstract Since the start of the 21st century, antibiotic drug discovery and development from natural products has experienced a certain renaissance. Currently, basic scientific research in chemistry and biology of natural products has finally borne fruit for natural product-derived antibiotics drug discovery. A batch of new antibiotic scaffolds were approved for commercial use, including oxazolidinones (linezolid, 2000), lipopeptides (daptomycin, 2003), and mutilins (retapamulin, 2007). Here, we reviewed the thiazolyl peptides (thiopeptides), an ever-expanding family of antibiotics produced by Gram-positive bacteria that have attracted the interest of many research groups thanks to their novel chemical structures and outstanding biological profiles. All members of this family of natural products share their central azole substituted nitrogen-containing six-membered ring and are classified into different series. Most of the thiopeptides show nanomolar potencies for a variety of Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumonia (PRSP). They also show other interesting properties such as antiplasmodial and anticancer activities. The chemistry and biology of thiopeptides has gathered the attention of many research groups, who have carried out many efforts towards the study of their structure, biological function, and biosynthetic origin. Here we reviewed a total of 119 natural thiopeptides discovered during the last 50 years. Moreover, we summarized biological profiles, mechanisms of action, and biosynthesis of these thiopeptides.

A structure–activity relationship study of phenyl sesquiterpenoids on efflux inhibition against Staphylococcus aureus Abstract Sixteen natural acetophenone sesquiterpene derivatives were isolated from Ferula ferulioides and 11 synthetic acetophenone sesquiterpene analogues were evaluated to explore the structure–activity relationships (SARs) on their antibacterial activities against a panel of bacteria including drug-resistant Staphylococcus aureus. The minimum inhibitory concentration (MIC) values of the compounds were in the range of 0.5–128 mg/L. Preliminary SAR studies showed that subtle modifications on both the 2',4'-dihydroxyphenyl moiety and the side chain reduced their activity against drug-resistant S. aureus. All of the compounds that showed no or only weak direct antibacterial activity were tested for their efflux inhibitory effects, among which four compounds showed significant efflux inhibition against drug-resistant strains. Natural product 14 showed significant inhibitory effects for EtBr efflux in strain SA1199B, which has reduced susceptibility to fluoroquinolones by efflux. Compounds 5, 14 and F-3 moderately inhibited EtBr efflux in the macrolide-resistant strain RN4220 and compound 13moderately inhibited efflux in an MRSA and effluxing tetracycline-resistant strain.

Synthesis of oleanolic acid/ursolic acid/glycyrrhetinic acid-hydrogen sulfide donor hybrids and their antitumor activity Abstract A total of 25 targeted hydrogen sulfide donor–pentacyclic triterpene hybrids were designed, synthesized and evaluated on the basis of inspiring reports about hydrogen sulfide donor molecules and oleanolic acid derivatives on anti-tumor activity. The results revealed that only some hybrids (10a, 10b, 12a, 12b, 13a, and 15b) showed moderate anti-proliferation activity against K562 cell line. It indicated that oleanane-type, (R)-lipoic acid and TBZ groups were much more favorable to the anti-proliferation activity. Furthermore, C-3 OH was more beneficial than C-28/29 COOH in the oleanane-type to the antitumor activity of the batch of (R)-lipoic acid derivatives. And among them, only compound 13a exhibited moderate anti-proliferation activity against both K562 and K562/ADR cell lines, while it exhibited no anti-proliferation activity against BEL-7402 and L-O2 cell lines. Therefore, it suggested that it was not suitable for hybridization of hydrogen sulfide donors attached to oleanolic acid, ursolic acid and glycyrrhetinic acid in the field of anti-tumor.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

General Thoracic and Cardiovascular Surgery

A case of type A acute aortic dissection with a common carotid trunk Abstract We present a rare case of common carotid artery with acute type A aortic dissection. A 72-year-old woman underwent emergent aortic arch repair using Antegrade selective cerebral protection. Bottom-tapped cannulae were inserted into three orifices of arch vessels, however, regional cerebral oxygen saturation decreased after rewarming. We found that arch branches were in order from front to back, right subclavian artery, common carotid trunk, and left subcravian artery. The patient complicated stroke in the right middle cerebral artery.

Intraoperative displacement of a Perceval sutureless prosthesis Abstract We describe a patient with mitral incompetence and aortic stenosis who underwent mitral valve repair and aortic valve replacement using a Perceval sutureless bioprosthesis. After weaning from cardiopulmonary bypass, repeated mitral valve repair was required due to residual mitral regurgitation. During this procedure, the aortic prosthesis was displaced, most likely by undue inadvertent traction on the atrial retractor, requiring its removal and reinsertion. When employing a sutureless valve gentle manipulation of the heart is mandatory to avoid possible adverse events as that herein described. Should this happen, the Perceval valve can be easily removed and repositioned.

Living-donor lung transplantation after surgical repair of transposition of the great arteries Abstract Pediatric pulmonary hypertension after surgery for congenital heart disease is a significant complication. We present a case of living-donor lung transplantation for a 12-year-old girl with pulmonary hypertension after surgical repair of transposition of great arteries. Despite repairing the transposition of great arteries, her growth was severely restricted because of progressive pulmonary hypertension; thus, lung transplantation was discussed. Standard bilateral lobar transplantation seemed unfeasible due to oversized grafts, so we performed a single lobar transplantation. Unexpectedly, she developed complications and died 3 months postoperatively despite another emergent lobar transplantation. We discussed the challenges and potential solutions regarding lobar size mismatching.

It is time to consider incorporating sarcopenia assessment in the surgical management of non-small-cell lung cancer

Novel harvesting technique of no-touch saphenous vein graft using THUNDERBEAT Abstract The no-touch technique of saphenous vein involves harvesting the vein as a pedicled graft and avoidance of direct contact with the vein or excessive high-pressure expansion. This technique provides long-term graft patency as that of internal mammary artery; however, the wound complications could be greater than conventional skeletonized technique. To solve the problem of leg wound trouble and to harvest the vein simpler, we have developed a novel harvesting technique using a newly developed energy device, THUNDERBEAT. This technique has the ability of efficacious tissue dissection, safer sealing of branches, and less wound complications without thermal damage to the graft. This strategy was successfully used in 35 patients.

Case report of cardiac herniation after sleeve pneumonectomy with superior vena cava reconstruction Abstract Cardiac herniation is a complication that occurs after intrapericardial pneumonectomy. It is life-threatening unless promptly diagnosed and surgery performed. We report a case of cardiac herniation after right intrapericardial pneumonectomy following radiotherapy for lung cancer. The patient developed cardiac herniation with sudden hypotension following a switch to the spine position. An immediate switch to the lateral decubitus position improved the cardiocirculatory dynamics, and surgical patch closure was performed. The circulation dynamics was unstable for several hours after surgery with elevated enzyme levels, which improved 2 days later. Immediate thoracotomy before irreversible myocardial damage resulted in a successful outcome. The risk of cardiac herniation should always be considered after intrapericardial pneumonectomy.

Preoperative biopsy does not affect postoperative outcomes of resectable non-small cell lung cancer Abstract Objectives Preoperative diagnostic interventions such as transbronchial biopsy and/or computed tomography-guided biopsy inevitably disrupt the lung structures and may disseminate tumour cells into the airway, vessels, or pleural cavity. Therefore, these procedures may affect the postoperative outcomes. Thus, we aimed to compare the survival outcomes in patients diagnosed by transbronchial biopsy vs computed tomography-guided biopsy vs lung resection. Methods In a single-institution retrospective analysis, data from consecutive patients with cTanyN0M0 lung cancer, who underwent surgery between January 2006 and December 2012, were extracted by chart review. The overall and recurrence-free survivals of patients diagnosed by transbronchial biopsy, computed tomography-guided biopsy, and lung resection were compared using the univariate and multivariate Cox proportional hazard models. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. Results Transbronchial biopsy and/or computed tomography-guided biopsy were performed for larger and more advanced tumours, than lung resection (intra- or postoperative-diagnosis group). At crude analysis, transbronchial biopsy group and computed tomography-guided biopsy group showed higher probability of pleural dissemination, and worse prognosis than the lung resection group. At multivariate analysis, the diagnostic methods were not identified as independent risk factors of pleural dissemination, overall survival, or recurrence-free survival. Conclusions Preoperative diagnostic interventions did not affect the relapse risk and prognosis, in this study cohort. Thus, preoperative diagnostic intervention is recommended if deemed necessary.

Lung transplantation via cardiopulmonary bypass: excellent survival outcomes from extended criteria donors Abstract Objectives The role of intraoperative cardiopulmonary bypass (CPB) in lung transplant (LTx) surgery is controversial. CPB enables slow pulmonary reperfusion and initial ventilation with low oxygen concentrations, both theoretically protective of transplanted lungs. In this study, we explored clinical outcomes following extended criteria donor LTx surgery implementing a thoroughly protective allograft reperfusion strategy using CPB. Methods Thirty-nine consecutive adult patients who underwent bilateral LTx with elective CPB and protective allograft reperfusion were reviewed. Bilaterally implanted lungs were reperfused simultaneously, via slow CPB flow reduction and initial ventilation with 21% oxygen and nitric oxide, followed by a brief modified ultrafiltration. During weaning from CPB, mean pulmonary arterial pressure was strictly maintained at 10–15 mmHg by controlling CPB and pulmonary flow. The clinical outcomes in 23 patients who received lungs from extended criteria donors (ECD group) were elucidated and compared to 16 patients undergoing LTx from standard criteria donors (SCD group). Results No life-threatening deterioration was observed to graft functionality during the first 72 h after LTx in the ECD group; however, only one patient required post-transplant extracorporeal membrane oxygenation. In three of 23 ECD LTx patients (12%), surgical revision for bleeding was required. Survival outcomes for the ECD group were favorable, with 100% survival at 6-months, 87.0% at 1-year, and 80.7% at 5-years. Outcomes in the ECD group were comparable to those in the SCD group. Conclusions Despite a certain extent of risk associated with full-dose heparinization, use of CPB does not undermine survival outcomes after ECD LTx surgery if protective allograft reperfusion is securely performed.

Transfer of a minimally invasive mitral valve repair program from a high-volume center to a very low volume center: how many cases are necessary to maintain acceptable results? Abstract Objective To investigate whether minimally invasive mitral valve repair (MIMVR) can be transferred from a high-volume center into a very small volume center and to clarify how many cases are necessary for maintenance of this program, early outcomes of MIMVR in Asahikawa Medical University were compared with those results in patients operated by a single surgeon in Duesseldorf University Hospital. Methods Sixty-five patients who underwent MIMVR in Asahikawa Medical University (group A) between May 2014 and July 2018 and 134 patients who underwent MIMVR in Duesseldorf University Hospital (group D) between September 2009 and January 2014 by a surgeon who started MIMVS later in Asahikawa were retrospectively analyzed. Results In group D, there were more patients with ischemic mitral valve regurgitation and with annular calcification than in group A. Survival rate at 6 months and 1 year was 98.5% and 98.5% in group A and 92.9% and 91.3% in group D, respectively. EuroSCORE II was significantly higher in patients dead within 30 days and within the first year. Conclusions The present study demonstrated that MIMVR programs can be transferred with acceptable early results into very low volume centers, if the team is developed by surgeons who are well trained and experienced in MIMVR. Moreover, the present study suggested that case number for maintenance of acceptable results may be obviously less than the previous recognition that this kind of specialized surgery could be maintained with at least 50 cases annually. However, meticulous preparations for surgery are essential for satisfactory surgical outcomes.

Malperfusion in type A aortic dissection: results of emergency central aortic repair Abstract Background Although outcomes of acute type A aortic dissection (ATAAD) have improved, malperfusion remains associated with high morbidity and mortality rates, and its optimal therapeutic treatment is unknown. Emergency central repair has been performed as our first-line approach for malperfusion. Here, we analyzed outcomes of ATAAD with malperfusion and reassessed emergency central repair. Methods In total, 1026 ATAAD patients underwent emergency surgery within 48 h of symptom onset, of whom 318 (30.9%) patients complicated with any preoperative malperfusion were included. Pathophysiology of malperfusion and surgical outcomes were analyzed. Results The in-hospital mortality rate was 12.9% for patients with malperfusion and 4.8% for patients without malperfusion (p < 0.0001). Coronary malperfusion was complicated in 7.5% of patients (% dead per group, 19.5%), mesenteric malperfusion in 3.6% (24.3%), renal malperfusion in 8.8% (14.4%), lower leg malperfusion in 12.6% (13.7%), brain malperfusion in 9.7% (12.0%), and spinal malperfusion in 1.1% (18.2%). Mortality rates varied substantially according to the number of affected organ systems (none, 4.8%; one system, 10.4%; two systems, 14.5%; three systems, 30.0%, and four systems; 30.3%; p < 0.0001). In malperfused patients, logistic regression analysis revealed that obesity (body mass index > 30 kg/m2), preoperative shock (systolic blood pressure < 80 mmHg), and visceral ischemia were independent predictors for hospital death. Conclusions Malperfusion of more organ systems and mesenteric malperfusion resulted in unfavorable prognosis, and effects of central repair were limited in such severe/complex malperfusion. To further improve outcomes of ATAAD with malperfusion, emergency reperfusion of affected organs followed by central repair might be considered.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Brain Structure and Function

The effect of exercise on memory and BDNF signaling is dependent on intensity Abstract The aims of the present study were to investigate in brain of adult rats (1) whether exercise-induced activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is dependent on exercise intensity modality and (2) whether exercise-induced improvement of memory is proportional to this pathway activation. Wistar rats were subjected to low (12 m/min) or high (18 m/min) exercise intensity on horizontal treadmill (30 min/day, 7 consecutive days) that corresponds to ~ 40 and 70% of maximal aerobic speed, respectively. Animals treated with scopolamine to induce memory impairment were subjected to novel object recognition test to assess potential improvement in cognitive function. Expressions of BDNF, phosphorylated TrkB receptors, synaptophysin (a marker of synaptogenesis), c-fos (a neuronal activity marker) and phosphorylated endothelial nitric oxide synthase (a cerebral blood flow marker) were measured in prefrontal cortex and hippocampus of different groups of rats. In terms of cognition, our data reported that only the most intense exercise improves memory performance. Our data also revealed that BDNF pathway is dependent on intensity modality of exercise with a gradual effect in hippocampus whereas only the highest intensity leads to this pathway activation in prefrontal cortex. Our study revealed that memory improvement through BDNF pathway activation is dependent on exercise intensity. While reporting that our protocol is sufficient to improve cognition in animals with impaired memory, our data suggest that prefrontal cortex is possibly a more suitable structure than hippocampus when neuroplastic markers are used to mirror potential improvement in memory performance.

On the existence of mechanoreceptors within the neurovascular unit of the mammalian brain Abstract We describe a set of perivascular interneurons (PINs) with series of fibro-vesicular complexes (FVCs) throughout the gray matter of the adult rabbit and rat brains. PIN–FVCs are ubiquitous throughout the brain vasculature as detected in Golgi-impregnated specimens. Most PINs are small, aspiny cells with short or long (> 1 mm) axons that split and travel along arterial blood vessels. Upon ramification, axons form FVCs around the arising vascular branches; then, paired axons run parallel to the vessel wall until another ramification ensues, and a new FVC is formed. Cytologically, FVCs consist of clusters of perivascular bulbs (PVBs) encircling the precapillary and capillary wall surrounded by end-feet and the extracellular matrix of endothelial cells and pericytes. A PVB contains mitochondria, multivesicular bodies, and granules with a membranous core, similar to Meissner corpuscles and other mechanoreceptors. Some PVBs form asymmetrical, axo-spinous synapses with presumptive adjacent neurons. PINs appear to correspond to the type 1 nNOS-positive neurons whose FVCs co-label with markers of sensory fiber-terminals surrounded by astrocytic end-feet. The PIN is conserved in adult cats and rhesus monkey specimens. The location, ubiquity throughout the vasculature of the mammalian brain, and cytological organization of the PIN–FVCs suggests that it is a sensory receptor intrinsic to the mammalian neurovascular unit that corresponds to an afferent limb of the sensorimotor feed-back mechanism controlling local blood flow.

Phonological picture–word interference in language mapping with transcranial magnetic stimulation: an objective approach for functional parcellation of Broca's region Abstract Functional imaging data suggest different regions for semantic, syntactic, and phonological processing in an anterior-to-posterior direction along the inferior frontal gyrus. Language mapping by use of neuro-navigated transcranial magnetic stimulation (TMS) is frequently applied in clinical research to identify language-related cortical regions. Recently, we proposed a high spatial resolution approach for more detailed language mapping of cortical sub-areas such as Broca's region. Here, we employed a phonological picture–word interference paradigm in healthy subjects to reveal functional specialization in Broca's region for phonological processing. The behavioral phonological priming effect is characterized by accelerated naming responses to target pictures accompanied by phonologically related auditory distractor words. We hypothesized that the inhibitory effects of TMS on language processing would reduce phonological priming only at stimulation sites involved in phonological processing. In active as compared to sham TMS, we found reduced phonological facilitation specifically at sites overlapping with the probabilistic cytoarchitectonic area 44. Our findings complemented functional imaging data by revealing structure–function relationship in Broca's region. The introduction of a reaction time based interference paradigm into TMS language mapping increases the objectivity of the method and allows to explore functional specificity with high temporal resolution. Findings may help to interpret results in clinical applications.

Thyroid hormone availability in the human fetal brain: novel entry pathways and role of radial glia Abstract Thyroid hormones (TH) are crucial for brain development; their deficiency during neurodevelopment impairs neural cell differentiation and causes irreversible neurological alterations. Understanding TH action, and in particular the mechanisms regulating TH availability in the prenatal human brain is essential to design therapeutic strategies for neurological diseases due to impaired TH signaling during neurodevelopment. We aimed at the identification of cells involved in the regulation of TH availability in the human brain at fetal stages. To this end, we studied the distribution of the TH transporters monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1), as well as the TH-metabolizing enzymes types 2 and 3 deiodinases (DIO2 and DIO3). Paraffin-embedded human brain sections obtained from necropsies of thirteen fetuses from 14 to 38 gestational weeks were analyzed by immunohistochemistry and in situ hybridization. We found these proteins localized along radial glial cells, in brain barriers, in Cajal-Retzius cells, in migrating fibers of the brainstem and in some neurons and glial cells with particular and complex spatiotemporal patterns. Our findings point to an important role of radial glia in controlling TH delivery and metabolism and suggest two additional novel pathways for TH availability in the prenatal human brain: the outer, and the inner cerebrospinal fluid–brain barriers. Based on our data we propose a model of TH availability for neural cells in the human prenatal brain in which several cell types have the ability to autonomously control the required TH content.

Relations between cognitive and motor deficits and regional brain volumes in individuals with alcoholism Abstract Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.

Localization, distribution and expression of growth hormone in the brain of Asian Catfish, Clarias batrachus Abstract Intense immunoreactivity was observed in several neurons of the nucleus preopticus (NPO) located in the preoptic area (POA), in addition to several GH cells in the proximal pars distalis (PPD) of the pituitary gland of Clarias batrachus. The immunoreactive cells were located in the paraventricular as well as supraoptic subdivisions of the NPO. GH immunoreactive fibers projecting from the neurons were traced caudally to the pituitary gland via the conspicuous preoptico-hypophysial tract (PHT) in the ventral tuberal area to the neurohypophysis of the pituitary. Apart from these immunoreactive fibers in the preoptico-hypophysial tract, some fine caliber fiber probably arising from the neurons located dorsally in the NPO also showed GH immunoreactivity, and these fibers constituted an independent tract. Bilaterally, it extended caudally through the dorsal hypothalamus almost as far as the saccus vasculosus where it curved sharply to descend into the caudal tuberal region and finally entered into the pituitary gland. The fibers of this tract were mainly distributed in the rostral pars distalis (RPD). This tract is quite distinct from the preoptico-hypophysial tract and herein called as the accessory preoptico-hypophysial tract (APHT). Expression of GH mRNA in the NPO was found 65-fold more than that of the control region, rostral cerebellum. These results altogether suggest that GH secreted by NPO neurons might serve as a neuro-modulatory role in the brain of C. batrachus. Transportation of GH to the pituitary via two independent tracts may represent the duality of neuroendocrine function. The present study underscores the possibility that GH in the brain of vertebrates may be a phylogenetically conserved phenomenon and provide clues to our understanding of the evolutionary course taken by the hormone.

Enhanced insular/prefrontal connectivity when resisting from emotional distraction during visual search Abstract Previous literature demonstrated that the processing of emotional stimuli can interfere with goal-directed behavior. This has been shown primarily in the context of working memory tasks, but "emotional distraction" may affect also other processes, such as the orienting of visuo-spatial attention. During fMRI, we presented human subjects with emotional stimuli embedded within complex everyday life visual scenes. Emotional stimuli could be either the current target to be searched for or task-irrelevant distractors. Behavioral and eye-movement data revealed faster detection of emotional than neutral targets. Emotional distractors were found to be fixated later and for a shorter duration than emotional targets, suggesting efficient top-down control in avoiding emotional distraction. The fMRI data demonstrated that negative (but not positive) stimuli were mandatorily processed by limbic/para-limbic regions (namely, the right amygdala and the left insula), irrespective of current task relevance: that is, these regions activated for both emotional targets and distractors. However, analyses of inter-regional connectivity revealed a functional coupling between the left insula and the right prefrontal cortex that increased specifically during search in the presence of emotional distractors. This indicates that increased functional coupling between affective limbic/para-limbic regions and control regions in the frontal cortex can attenuate emotional distraction, permitting the allocation of spatial attentional resources toward task-relevant neutral targets in the presence of distracting emotional signals.

Memory-guided attention: bilateral hippocampal volume positively predicts implicit contextual learning Abstract Several studies have begun to demonstrate that contextual memories constitute an important mechanism to guide our attention. Although there is general consensus that the hippocampus is involved in the encoding of contextual memories, it is controversial whether this structure can support implicit forms of contextual memory. Here, we combine automated segmentation of structural MRI with neurobehavioral assessment of implicit contextual memory-guided attention to test the hypothesis that hippocampal volume would predict the magnitude of implicit contextual learning. Forty healthy subjects underwent 3T magnetic resonance imaging brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Implicit learning of contextual information was measured using the contextual cueing task. We found that both left and right hippocampal volumes positively predicted the magnitude of implicit contextual learning. Larger hippocampal volume was associated with superior implicit contextual memory performance. This study provides compelling evidence that implicit contextual memory-guided attention is hippocampus-dependent.

Role of the insula in top–down processing: an intracranial EEG study using a visual oddball detection paradigm Abstract Functional neuroimaging studies suggest that the insular cortex—and more especially the anterior insula (aI)—is involved in attentional processes and plays a crucial role in the "salience network". However, its specific role in attentional processing remains unclear, which is partly attributable to the low temporal resolution of non-invasive neuroimaging techniques. This study aims to examine the spatio-temporal dynamics of visual target processing using intracranial EEG recorded directly from the insula. Eight epileptic patients (four women, age 18–44 years) completed a three-stimulus visual oddball task during the extraoperative invasive intracranial EEG (iEEG) monitoring of their drug-resistant seizures. Depth electrodes were implanted in ten insular lobes (5 left and 5 right) and provided a total of 59 recording contacts in the insula. Event-related potentials (ERPs) and high-gamma-band responses (GBRs) were processed offline. Permutation analyses were performed to compare ERP signals across conditions during the P300 (225–400) interval, and modulations of GBRs (70−150 Hz) were computed for separate 100 ms time windows (from 0 to 1000 ms post-stimulus) and compared across conditions using non-parametric Wilcoxon test. Target stimuli were associated with a P300 (250–338 ms) component for 39% of contacts implanted in the aI, most probably reflecting voluntary attentional processing. Amplitude was significantly greater for target than for standard stimuli for all of these contacts, and was greater than for novel stimuli for 72%. In the posterior insula (pI), 16% of contacts showed preferential responses to target stimulus in the P300 interval. Increased GBRs in response to targets were observed in 53% of aI contacts (from ≈ 200 to 300 ms) and in 43% of pI contacts (from ≈ 400 to 500 ms). This study is the first to characterize the spatio-temporal dynamics of visual target processing in the insula using iEEG. Results suggest that visual targets elicit a P300 in the aI which corresponds in latency to the P3b component, suggesting that this region is involved in top–down processing of task-relevant information. GBRs to visual targets occur earlier in the aI than in the pI, further characterizing their respective roles in voluntary attentional processing.

Merlin modulates process outgrowth and synaptogenesis in the cerebellum Abstract Neurofibromatosis type 2 (NF2) patients are prone to develop glial-derived tumors in the peripheral and central nervous system (CNS). The Nf2 gene product –Merlin is not only expressed in glia, but also in neurons of the CNS, where its function still remains elusive. Here, we show that cerebellar Purkinje cells (PCs) of isoform-specific Merlin-deficient mice were innervated by smaller vGluT2-positive clusters at presynaptic terminals than those of wild-type mice. This was paralleled by a reduction in frequency and amplitude of miniature excitatory postsynaptic currents (mEPSC). On the contrary, in conditional transgenic mice in which Merlin expression was specifically ablated in PCs (L7Cre;Nf2fl/fl), we found enlarged vGluT2-positive clusters in their presynaptic buttons together with increased amplitudes of miniature postsynaptic currents. The presynaptic terminals of these PCs innervating neurons of the deep cerebellar nuclei were also enlarged. When exploring mice with Merlin-deficient granule cells (GCs) (Math1Cre;Nf2fl/fl), we found cerebellar extracts to contain higher amounts of vGluT1 present in parallel fiber terminals. In parallel, mEPSC frequency was increased in Math1Cre;Nf2fl/fl mice. On the contrary, VGluT2 clusters in cerebellar glomeruli composed of NF2-deficient presynaptic Mossy fiber terminals and NF2-deficient postsynaptic GC were reduced in size as shown for isoform-specific knockout mice. These changes in Math1Cre;Nf2fl/fl-deficient mice were paralleled by an increased activation of Rac1–Cofilin signaling which is known to impact on cytoskeletal reorganization and synapse formation. Consistent with the observed synaptic alterations in these transgenic mice, we observed altered ultrasonic vocalization, which is known to rely on proper cerebellar function. No gross morphological changes or motor coordination deficits were observed in any of these transgenic mice. We therefore conclude that Merlin does not regulate overall cerebellar development, but impacts on pre- and post-synaptic terminal organization.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com