Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety, and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and complex 2 (mTORC2) activities in the brain, given that both pathways may represent unique targets for treatment. METHODS: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes. Histological and immunohistochemical techniques were used to assess hippocampal and neocortical structural abnormalities and cell-specific expression of individual biomarkers. Samples from patients with focal cortical dysplasia (FCD) type II served as positive controls. RESULTS: We found significantly increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho-S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls, consistent with activation of both mTORC1 and mTORC2. Our work identified the phosphoinositide 3-kinase and Ras/extracellular signal-regulated kinase signaling pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we found that overactive mTORC2 signaling was accompanied by induction of two protein kinase B-dependent prosurvival pathways, as evidenced by increased inhibitory phosphorylation of forkhead box class O3a (Ser253) and glycogen synthase kinase 3 beta (Ser9). INTERPRETATION: Our data demonstrate that mTOR signaling is significantly dysregulated in human TLE, offering new targets for pharmacological interventions. Specifically, clinically available drugs that suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its analogs, may represent a new group of antiepileptogenic agents in TLE patients. Ann Neurol 2018;83:311-327.

Animal Models of Psychosis: Current State and Future Directions.

Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability.

Uso del hueso bovino en la fusión cervical sin instrumentación / Use of bovine bone in cervical fusion without instrumentation

INTRODUCCIÓN: Con el desarrollo de las ciencias médicas hoy es una realidad realizar injerto de órganos, y el reto está, en la disponibilidad de ellos, debido a su alta demanda. La búsqueda de materiales biocompatibles, tanto naturales como sintéticos o combinados, puede ayudar a resolver este déficit. OBJETIVO: Demostrar la factibilidad del uso de injerto óseo bovino en la fusión intersomática cervical. MÉTODOS: Se diseño un estudio descriptivo, retrospectivo y prospectivo, observacional de corte transversal, tipo serie de casos, en 10 pacientes portadores de enfermedad degenerativa discal cervical con afectación de uno o dos niveles, en los cuales fue ineficaz el tratamiento conservador, donde se colocaron 14 injertos bovinos diseñados para estos efectos. En 13 espacios se obtuvo la fusión, no lográndose solamente en uno la incorporación del injerto. Se evidenció una pérdida de la altura discal de más de 2 mm en 2 espacios y de menos de 2 mm en 11 espacios. En uno, el necrosado, se perdió totalmente. DISCUSIÓN: Los resultados obtenidos en nuestra serie son similares a los presentados por otros autores, en cuanto a rango de edad y numero de fusiones logradas. La principal deficiencia encontrada es la pérdida de la altura discal, que aunque en la mayoría, es de menos de 2 mm (que es un margen tolerable) al mantenerse clínicamente nuestros pacientes asintomáticos. CONCLUSIONES: Se evidencia la utilidad del diseño específico del injerto de hueso bovino en la fusión discal cervical anterior. Se recomienda el aumento de la resistencia mecánica a las cargas axiales, en su fabricación, para evitar la pérdida de la altura discal

INTRODUCTION: With the development of the medical sciences, nowadays it is a reality to perform organ grafts and the remainder is the availability, due to high demand. Search of biocompatible material, natural, synthetic or combined, may to help to solve this deficit. OBJECTIVE: To demonstrate de feasibility of bovine bone graft use in cervical intersomatic fusion. METHODS: An observational, prospective, retrospective and descriptive and cross-sectional study was conducted as cases-series in 10 patients presenting with a cervical disk degenerative disease involving one or two levels where conservative treatment fails placing 14 bovine grafts designed for this end. In 13 spaces fusion was achieved, except in one where graft incorporation was not possible. It was demonstrated a disc height loss of more than 2 mm in two spaces and less than 2 mm in 11 spaces. In one of them, the necrotizing one, there was a total loss. DISCUSSION: Results obtained in our series are similar to that of other authors as regards an age rank and the number of fusions achieved. The major difference found is the loss of disk height, that in mort, is less than 2 mm (tolerable margin) when our patients are clinically asymptomatic. CONCLUSIONS: It is demonstrated the usefulness of specific design of bovine bone graft in anterior cervical disk fusion. It is recommendable the increase of mechanical resistance of axial loads in its manufacture, to avoid the loss of disk height

Manejo del síndrome doloroso lumbar / Management of lumbar syndrome

Se realizó una revisión bibliográfica del síndrome doloroso lumbar y se seleccionaron los artículos relacionados con este síndrome publicados desde 1991 hasta 2009. Se hizo hincapié en la búsqueda de guías para el manejo del dolor lumbar en la práctica clínica, y sus criterios fueron revisados por el equipo de especialistas en Ortopedia y Traumatología del Servicio de columna vertebral del Hospital Ortopédico Docente Fructuoso Rodríguez y adaptados a las condiciones del Sistema Nacional de Salud cubano...

A bibliographic review on painful syndrome was made selecting the articles published from 1991 to 2009 related to this syndrome. Authors emphasize in the search of guides for management of lumbar pain in the clinical practice, whose criteria were analyzed by the team Orthopedics and Traumatology team of the spinal column service from the Fructuoso Rodríguez Hospital and adjusted to conditions of the Cuban Health System...