N-Methyl-d-Aspartate Receptor Modulation by Nicotinamide Adenine Dinucleotide Phosphate Oxidase Type 2 Drives Synaptic Plasticity and Spatial Memory Impairments in Rats Exposed Pre- and Postnatally to Ethanol.

Aims: Pre- and/or early postnatal ethanol exposure (prenatal alcohol exposure [PAE]) impairs synaptic plasticity as well as memory formation, but the mechanisms underlying these effects remain unclear. Both long-term potentiation (LTP) and spatial memory formation in the hippocampus involve the nicotinamide adenine dinucleotide phosphate oxidase type 2 (NOX2) enzyme. Previous studies have reported that N-methyl-d-aspartate receptor (NMDAR) activation increases NOX2-mediated superoxide generation, resulting in inhibition of NMDAR function, but whether NOX2 impacts NMDAR function in PAE animals leading to impaired LTP and memory formation remains unknown. We aim to evaluate whether the NOX2-NMDAR complex is involved in the long-lasting deleterious effects of PAE on hippocampal LTP and memory formation. Results: Here we provide novel evidence that PAE animals display impaired NMDAR-dependent LTP in the cornus ammonis field 1 (CA1) and NMDAR-mediated LTP in the dentate gyrus (DG). Moreover, PAE rats displayed increased NMDAR-mediated transmission in both hippocampal areas. Interestingly, NOX2 pharmacological inhibition restored NMDAR-mediated transmission and LTP in the CA1, but not in the DG. PAE also induced overexpression of NOX2 and CaMKII isoforms, but did not modify the content or the redox state of the N-methyl-d-aspartate receptor subunit-1 (NR1) subunit of NMDAR in both areas of the hippocampus. In addition, adolescent PAE rats orally fed the antioxidant and free radical scavenger apocynin exhibited significantly improved spatial memory acquisition. Innovation and Conclusion: By showing in PAE animals NOX2 overexpression and increased NMDAR-mediated transmission, which might lead to impaired synaptic plasticity and memory formation in a region-specific manner, we provide an important advance to our current understanding of the cellular mechanisms underlying PAE-dependent defective hippocampal function.

FACETS of health disparities in epilepsy surgery and gaps that need to be addressed.

PURPOSE OF REVIEW: Disparities in treatment and outcomes of patients with epilepsy have been identified in several distinct patient populations. The purpose of this review is to organize the literature and establish clear pathways as to why certain patient populations are not receiving epilepsy surgery. By establishing the acronym FACETS (fear of treatment, access to care, communication barriers, education, trust between patient and physician, and social support), we set up a pathway to further study this area in an organized fashion, hopefully leading to objective solutions. RECENT FINDINGS: Studies revealed that African American, Hispanic, and non-English-speaking patients underwent surgical treatment for epilepsy at rates significantly lower compared to white patients. SUMMARY: This article explains possible reasons outlined by FACETS for the health disparities in epilepsy surgery that exist in patients of a certain race, socioeconomic status, and language proficiency.

Bilateral Hip Arthroplasty: When Is It Safe to Operate the Second Hip? A Systematic Review.

INTRODUCTION: Patients with degenerative hip disease frequently present with bilateral involvement that requires surgical management. The main goal when treating these patients is to achieve the maximum efficiency without increasing risk of perioperative complications; therefore, the decision regarding the best moment to operate the second hip becomes relevant. Although studies have addressed this topic, whether a simultaneous or staged surgery should be performed remains controversial. The purpose of this study was to determine, based on available evidence, the optimum strategy in terms of safety to operate the second hip in patients with bilateral involvement. MATERIALS AND METHODS: A meta-analysis was planned. A systematic review of the literature was performed including clinical trials or observational analytical studies comparing the safety of bilateral arthroplasty performed simultaneously or staged by measuring major and minor complications. The appropriateness of a meta-analysis was evaluated through the detailed analysis of the risk of bias and clinical heterogeneity of the included studies. RESULTS: Thirteen studies were selected after the systematic review. A wide variability in the methodological designs was found with a critical risk of bias in most of them. Considerable heterogeneity was detected in defining staged surgery in the cointerventions and how the outcomes were defined and measured. In response to these findings, a meta-analysis was considered not appropriate. The results showed no differences in the risk of mortality or systemic complications in young and healthy patients between simultaneous or staged surgeries. However, increased risk of complications for staged surgeries performed during the same hospitalization was observed. CONCLUSIONS: Available evidence is very heterogeneous and the quality of evidence is low. The available evidence supports the performance of simultaneous hip arthroplasty in selected patients (not older than 65 years, ASA 1-2, without cardiovascular comorbidities) and suggests the avoidance of staged surgeries within the same hospitalization.

Characteristics of Emergency Medicine Residency Programs in Colombia.

INTRODUCTION: Emergency medicine (EM) is in different stages of development around the world. Colombia has made significant strides in EM development in the last two decades and recognized it as a medical specialty in 2005. The country now has seven EM residency programs: three in the capital city of Bogotá, two in Medellin, one in Manizales, and one in Cali. The seven residency programs are in different stages of maturity, with the oldest founded 20 years ago and two founded in the last two years. The objective of this study was to characterize these seven residency programs. METHODS: We conducted semi-structured interviews with faculty and residents from all the existing programs in 2013-2016. Topics included program characteristics and curricula. RESULTS: Colombian EM residencies are three-year programs, with the exception of one four-year program. Programs accept 3-10 applicants yearly. Only one program has free tuition and the rest charge tuition. The number of EM faculty ranges from 2-15. EM rotation requirements range from 11-33% of total clinical time. One program does not have a pediatric rotation. The other programs require 1-2 months of pediatrics or pediatric EM. Critical care requirements range from 4-7 months. Other common rotations include anesthesia, general surgery, internal medicine, obstetrics, gynecology, orthopedics, ophthalmology, radiology, toxicology, psychiatry, neurology, cardiology, pulmonology, and trauma. All programs offer 4-6 hours of protected didactic time each week. Some programs require Advanced Cardiac Life Support, Pediatric Advanced Life Support and Advanced Trauma Life Support, with some programs providing these trainings in-house or subsidizing the cost. Most programs require one research project for graduation. Resident evaluations consist of written tests and oral exams several times per year. Point-of-care ultrasound training is provided in four of the seven programs. CONCLUSION: As emergency medicine continues to develop in Colombia, more residency programs are expected to emerge. Faculty development and sustainability of academic pursuits will be critically important. In the long term, the specialty will need to move toward certifying board exams and professional development through a national EM organization to promote standardization across programs.

Occipital dysembryoplastic neuroepithelial tumor presenting as adult-onset temporal epilepsy.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor which commonly presents as childhood-onset temporal lobe epilepsy (TLE). We present a case of histologically proven DNET with a clinical presentation and scalp EEG suggestive of adult-onset TLE. MRI showed an occipital lesion. PET showed abnormal metabolism of the occipital lesion and the ipsilateral temporal lobe; raising concern for an abnormal functional network reorganization. Intracranial EEG showed interictal spikes and seizures originating from the occipital lesion with no seizures emanating from the temporal lobe. Occipital DNET due to their chronic nature can reorganize the network and mimic TLE.

Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity.

P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 Å resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions.

Clinical features and postoperative seizure outcome in patients with drug-resistant gelastic seizures without hypothalamic hamartoma.

OBJECTIVES: The objective of this study was to describe the clinical characteristics and surgical outcome in patients with gelastic seizures without hypothalamic hamartoma. METHODS: We retrospectively reviewed all the video-EEG reports over a 5-year period (2007-2011) for the occurrence of the terms "laugh" or "giggle" in the text body. All the patients with at least one documented gelastic seizure at the epilepsy monitoring unit were studied. In patients who underwent epilepsy surgery, seizure outcomes were analyzed. RESULTS: Sixteen patients (10 females and 6 males) with a mean age of 46.3years were studied. Seven patients had invasive intracranial EEG recordings. Seizure onset zone was in a temporal lobe in four patients and the frontal lobe in one patient. Two patients did not have gelastic seizures during their intracranial EEG monitoring. Nine patients underwent resective epilepsy surgery for their seizures. Six patients (67%) were seizure-free after surgery. CONCLUSION: In adult patients, gelastic seizures can be seen in patients with focal epilepsy without hypothalamic hamartoma. Nonhypothalamic hamartoma gelastic seizures originating from the temporal lobe can be amenable to surgery.

LGI1-negative faciobrachial dystonic-like seizures originating from the insula.

We expand the differential diagnosis of LGI1-positive faciobrachial dystonic seizures (FBDS) by presenting a 67-year-old woman affected by seizures of similar semiology who was found to have insular epilepsy. We report the distinct characteristics of insular faciobrachial dystonic-like seizures that would help clinicians to differentiate them from typical LGI1-positive FBDS, thus, guiding therapy while awaiting antibody results. LGI1-negative faciobrachial dystonic-like seizures should be considered when the seizure semiology includes unilateral and prolonged dystonia without loss of awareness, there is an ictal EEG correlate, MRI is suggestive of insular lesion, and when there is neither clearly associated memory impairment nor hyponatremia.

Síndrome HaNDL / Síndrome HaNDL / HaNDL Syndrome

Introducción: El Síndrome HaNDL (Headache and neurologic deficits with cerebroespinal fluid lymphocytosis) por sus siglas en inglés, es una patología que cursa con cefalea, focalización neurológica y linfocitosis en el líquido cefalorraquídeo. Objetivo: este artículo busca presentar un caso de Síndrome de HaNDL, puesto que esta condición nosológica implica un reto diagnóstico. Resultados y conclusiones: Se presenta el caso de un paciente con diagnóstico de síndrome de HaNDL los hallazgos al examen físico y del líquido cefalorraquídeo.

Introduction: The syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis, is a pathology that presents cephalalgia, neurological focalization and lymphocytes in the cerebrospinal fluid. Objective: This article presents a HaNDL Syndrome case, since this nosological condition implies a diagnostic challenge. Results and conclusions: A case of a patient with HaNDL syndrome diagnosis, physical examination findings and cerebrospinal fluid are presented.

Introdução: A síndrome de HaNDL (Headache and neurologic déficits with cerebrospinal fluid lymphocytosis) por sua sigla em inglês é uma doença que causa dor de cabeça, foco neurológico e linfocitose no líquido cefalorraquidiano. Objetivo: Este artigo tem como objetivo apresentar um caso de Síndrome de HaNDL, uma vez que esta condição nosológica envolve um desafio diagnóstico. Resultados e conclusões: Apresenta-se o caso de um paciente diagnosticado com a síndrome de HaNDL, o encontrado no exame físico e o líquido cefalorraquidiano.

Factores de riesgo para infección respiratoria aguda baja grave en Bogotá, 2001 / Risk factors for low acute respiratory infection in Bogotá: a 2001 survey

La gravedad de la infección respiratoria aguda (IRA) es mayor en países en desarrollo, sobre todo entre grupos social y económicamente pobres. Las neumonías virales son las más comunes, especialmente en niños. Con el fin de medir algunos factores asociados con formas graves de infección respiratoria baja realizamos un estudio de casos y controles prospectivo y de base hospitalaria en Bogotá entre noviembre de 2000 y agosto de 2001. Los casos fueron niños entre 2 meses y 5 años que llenaban los criterios de la OMS para IRA grave o muy grave. Los controles eran niños con IRA en el mismo rango de edad, que consultaban al mismo hospital y que no presentaban tirajes. Se estudiaron 638 niños entre los 2 meses y los 5 años de edad (277 casos y 361 controles). Los factores más importantes fueron: vivienda en préstamo (OR2,7; IC95 por ciento: 1,06-7,07), compartir la cama (OR1,88; IC95 por ciento: 1,0-3,7), más de 9 personas en la misma casa (OR1,82; IC95 por ciento: 1,0-3,51) y fumadores en la vivienda (OR1,4; IC95 por ciento: 1,0-2,05). Se tomaron 114 muestras nasofaríngeas (niños con 3 días de haber iniciado síntomas) y se obtuvieron virus en 98 de ellas, y se identificó el virus sincitial respiratorio en 41,8 por ciento, virus influenza A en 3,1 por ciento y virus influenza B en 1 por ciento. El 100 por ciento de los aislamientos positivos para influenza A y B fueron enviados al CDC en Atlanta, donde fueron clasificados como influenza A/PANAMA/2007/99-like e influenza B/SICHUAN/379/99-like, respectivamente.

Resultados del tratamiento del sindrome de pinzamiento subacronial sin lesión del manguito rotador: acromioplastia artroscópica versus acromioplastia abierta por técnica de "mini-incisión" / Results of treatment of subacromial impingement syndrome without injury of rotator cuff: arthroscopic acromioplasty vs. open acromioplasty for mini-incision technique

La cirugía de descompresión del espacio subacromial es, en a actualidad, una solución válida para el sindrome de pinzamiento del hombro refractario al tratamiento conservador. Existen dos alternativas: la acromioplastia abierta -incluyendo los abordajes por "mini-incision" y la artroscopica. el tratamiento artroscopico ofrece ventajas teóricas en cuanto a extensión de la agresión quirúrgica, menor dolor y tiempo de retorno a las actividades fisicas normales, pero tiene limitaciones dadas principalmente por la infraestructura y el entrenamiento específico necesarios para su realización. A la vez, el tratamiento abierto ofrece ventajas tales como su mayor accesibilidad para el ortopedista y menores costos tanto medicos como institucionales con un mayor tiempo de rehabilitación. Presentamos un estudio observacional analítico, tipo cohorte, prospectivo, conformado por dos grupos de pacientes similares, con edades entre 40 y 50 años, con diagnóstico de sindrome de pinzamiento subacromial sin ruptura del manguito rotador, en el cual se compararon los resultados obtenidos con la descompresión mediante acromioplastia artroscópica vs. la técnica abierta con "mini-incision", teniendo en cuenta variables como la escala UCLA a los 30, 90 y 180 dias postoperatorios. Se encontraron diferencias estadisticamente significativas en los resultados catalogados como buenos y excelente a favor de la técnica artroscópica a los 30 dias pero no asi, a los 90 y 180 dias de seguimiento, igualandose los resultados entre los dos grupos al final del mismo.

Infecciones por Haemophilus influenzae en la población pediátrica / Haemophilus influenzae infections in children

Haemophilus influenzae es un microorganismo causante de una variada gama de patologías en diferentes segmentos de la población, especialmente en la población pediátrica, en la cual representa una carga importante en morbilidad, mortalidad y gastos en salud a nivel mundial. Las infecciones por este agente cubren un gran espectro que va desde colonización asintomática del tracto respiratorio superior, infecciones superficiales y localizadas hasta afecciones sistémicas graves como sepsis, meningitis o epiglotitis. Se hace una revisión actualizada de la infección por H. influenzae, con especial énfasis en los aspectos microbiológicos, de su patogenia, la epidemiología los procedimientos de diagnóstico y de tratamiento, y se incluyen algunos comentarios sobre las enfermedades específicas causadas por este agente patógeno, mencionando, también, las estrategias de prevención y el impacto de la vacunación contra este agente