Graph neural networks in EEG spike detection.

OBJECTIVE: This study develops new machine learning architectures that are more adept at detecting interictal epileptiform discharges (IEDs) in scalp EEG. A comparison of results using the average precision (AP) metric is made with the proposed models on two datasets obtained from Baptist Hospital of Miami and Temple University Hospital. METHODS: Applying graph neural networks (GNNs) on functional connectivity (FC) maps of different frequency sub-bands to yield a novel architecture we call FC-GNN. Attention mechanism is applied on a complete graph to let the neural network select its important edges, hence bypassing the extraction of features, a model we refer to as CA-GNN. RESULTS: On the Baptist Hospital dataset, the results were as follows: Vanilla Self-Attention →0.9029±0.0431, Hierarchical Attention →0.8546±0.0587, Vanilla Visual Geometry Group (VGG) →0.92±0.0618, Satelight →0.9219±0.046, FC-GNN →0.9731±0.0187, and CA-GNN →0.9788±0.0125. In the same order, the results on the Temple University Hospital dataset are 0.9692, 0.9113, 0.97, 0.9575, 0.963, and 0.9879. CONCLUSION: Based on the good results they yield, GNNs prove to have a strong potential in detecting epileptogenic activity. SIGNIFICANCE: This study opens the door for the discovery of the powerful role played by GNNs in capturing IEDs, which is an essential step for identifying the epileptogenic networks of the affected brain and hence improving the prospects for more accurate 3D source localization.

Dynamics and Distant Effects of Frontal/Temporal Epileptogenic Focus Using Functional Connectivity Maps.

OBJECTIVE: Connectivity patterns of interictal epileptiform discharges are all subtle indicators of where the three-dimensional (3D) source of a seizure could be located. These specific patterns are explored in the recorded electroencephalogram (EEG) signals of 20 individuals diagnosed with focal epilepsy to assess how their functional brain maps could be affected by the 3D onset of a seizure. METHODS: Functional connectivity maps, estimated by phase synchrony among EEG electrodes, were obtained by applying a data-driven recurrence-based method. This is augmented through a novel approach for selecting optimal parameters that produce connectivity matrices that are deemed significant for assessing epileptiform activity in context to the 3D source localization of seizure onset. These functional connectivity matrices were evaluated in different brain areas to gauge the regional effects of the 3D epileptic source. RESULTS: Empirical evaluations indicate high synchronization in the temporal and frontal areas of the effected epileptic hemisphere, whereas strong links connect the irritated area to frontal and temporal lobes of the opposite hemisphere. CONCLUSION: Epileptic activity originating in the temporal or frontal areas is seen to affect these areas in both hemispheres. SIGNIFICANCE: The results obtained express the dynamics of focal epilepsy in context to both the epileptogenic zone and the affected distant areas of the brain.

Monoamine Release in the Cat Lumbar Spinal Cord during Fictive Locomotion Evoked by the Mesencephalic Locomotor Region.

Spinal cord neurons active during locomotion are innervated by descending axons that release the monoamines serotonin (5-HT) and norepinephrine (NE) and these neurons express monoaminergic receptor subtypes implicated in the control of locomotion. The timing, level and spinal locations of release of these two substances during centrally-generated locomotor activity should therefore be critical to this control. These variables were measured in real time by fast-cyclic voltammetry in the decerebrate cat's lumbar spinal cord during fictive locomotion, which was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) and registered as integrated activity in bilateral peripheral nerves to hindlimb muscles. Monoamine release was observed in dorsal horn (DH), intermediate zone/ventral horn (IZ/VH) and adjacent white matter (WM) during evoked locomotion. Extracellular peak levels (all sites) increased above baseline by 138 ± 232.5 nM and 35.6 ± 94.4 nM (mean ± SD) for NE and 5-HT, respectively. For both substances, release usually began prior to the onset of locomotion typically earliest in the IZ/VH and peaks were positively correlated with net activity in peripheral nerves. Monoamine levels gradually returned to baseline levels or below at the end of stimulation in most trials. Monoamine oxidase and uptake inhibitors increased the release magnitude, time-to-peak (TTP) and decline-to-baseline. These results demonstrate that spinal monoamine release is modulated on a timescale of seconds, in tandem with centrally-generated locomotion and indicate that MLR-evoked locomotor activity involves concurrent activation of descending monoaminergic and reticulospinal pathways. These gradual changes in space and time of monoamine concentrations high enough to strongly activate various receptors subtypes on locomotor activated neurons further suggest that during MLR-evoked locomotion, monoamine action is, in part, mediated by extrasynaptic neurotransmission in the spinal cord.

Spontaneous and electrically-evoked catecholamine secretion from long-term cultures of bovine adrenal chromaffin cells.

Catecholamine release was measured from bovine adrenal medullary chromaffin cell (CC) cultures maintained over a period of three months. Cells were plated over simple biocompatible cell platforms with electrical stimulation capability and at specified times transferred to an acrylic superfusion chamber designed to allow controlled flow of superfusate over the culture. Catecholamine release was measured from the superfusates using fast cyclic voltammetry before, during and after electrical stimulation of the cells. Immunocytochemical staining of CC cultures revealed that they were composed of epinephrine (EP) and/or norepinephrine (NE) type cells. Both spontaneous and evoked-release of catecholamines from CCs were observed throughout the testing period. EP predominated during spontaneous release, whereas NE was more prevalent during electrically-evoked release. Electrical stimulation for 20 s, increased total catecholamine release by 60-130% (measured over a period of 500 s) compared to that observed for an equivalent 20 s period of spontaneous release. Stimulus intensity was correlated with the amount of evoked release, up to a plateau which was observed near the highest intensities. Shorter intervals between stimulation trials did not significantly affect the initial amount of release, and the amount of evoked release was relatively stable over time and did not decrease significantly with age of the culture. The present study demonstrates long-term survival of CC cultures in vitro and describes a technique useful for rapid assessment of cell functionality and release properties of cultured monoaminergic cell types that later can be transplanted for neurotransmitter replacement following injury or disease.

Evaluación de diferentes pruebas para el diagnóstico de H. pylori / Evaluation of different tests to diagnose H. pylori

Introducción: todos los métodos disponibles para el diagnóstico de H. pylori tienen diferencias en su sensibilidad y especificidad. El propósito de este estudio es determinar el índice de desempeño, sensibilidad, especificidad y valores predictivos de cuatro métodos invasivos, teniendo como técnica de referencia la definición de caso: cultivo positivo o la concordancia de por lo menos dos procesos de diagnósticos positivos. Metodología: a setenta y dos pacientes se les tomaron cinco biopsias distribuidas para PCR-ureC, cultivo, prueba rápida de ureasa (PRU) y examen histológico (EH). Resultados: los índices de desempeño (ID), sensibilidad, especificidad y valores predictivos mostraron diferencias. La pareja EH-PCR tuvo eficacia considerable por presentar los mayores valores en los índices analizados. La prevalencia de lainfección fue de 86.1%. Conclusión: para establecer el verdadero estatus de la infección por H. pylori, se debe utilizar el criterio de definición de caso.

Introduction: all of the available tests for the diagnosis of H. pylori have differencesin their sensibility and specificity. The purpose of this study is to determine thedevelopmental index, sensibility, specificity and predictable values of four invasive methods, using the case definition as a referential technique; positive culture o concordance of at least two processes of positive diagnostics.Methods: five biopsies were taken among seventy two patients, distributed for PCR-ureC, culture, quick ureic test (PRU) and histological examination (EH).Results: the developmental index (ID), sensibility, specificity and predictivemeasures showed differences. The couple EH-PCF was considerably effective, presenting the greatest values of analyzed indexes. The prevalence of infection was of 86.1%. Conclusion: in order to establish the true status of the infection by H. pylori, it is necessary to use the criteria by case definition.

Locomotor-activated neurons of the cat. II. Noradrenergic innervation and colocalization with NEα 1a or NEα 2b receptors in the thoraco-lumbar spinal cord.

Norepinephrine (NE) is a strong modulator and/or activator of spinal locomotor networks. Thus noradrenergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the noradrenergic innervation of functionally related, locomotor-activated neurons within the thoraco-lumbar spinal cord. This was accomplished by immunohistochemical colocalization of noradrenergic fibers using dopamine-ß-hydroxylase or NEα(1A) and NEα(2B) receptors with cells expressing the c-fos gene activity-dependent marker Fos. Experiments were performed on paralyzed, precollicular-postmamillary decerebrate cats, in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. The majority of Fos labeled neurons, especially abundant in laminae VII and VIII throughout the thoraco-lumbar (T13-L7) region of locomotor animals, showed close contacts with multiple noradrenergic boutons. A small percentage (10-40%) of Fos neurons in the T7-L7 segments showed colocalization with NEα(1A) receptors. In contrast, NEα(2B) receptor immunoreactivity was observed in 70-90% of Fos cells, with no obvious rostrocaudal gradient. In comparison with results obtained from our previous study on the same animals, a significantly smaller proportion of Fos labeled neurons were innervated by noradrenergic than serotonergic fibers, with significant differences observed for laminae VII and VIII in some segments. In lamina VII of the lumbar segments, the degree of monoaminergic receptor subtype/Fos colocalization examined statistically generally fell into the following order: NEα(2B) = 5-HT(2A) ≥ 5-HT(7) = 5-HT(1A) > NEα(1A). These results suggest that noradrenergic modulation of locomotion involves NEα(1A)/NEα(2B) receptors on noradrenergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. Further study of the functional role of these receptors in locomotion is warranted.

Locomotor-activated neurons of the cat. I. Serotonergic innervation and co-localization of 5-HT7, 5-HT2A, and 5-HT1A receptors in the thoraco-lumbar spinal cord.

Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT(7)/5-HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80-100%) of locomotor cells, which were most abundant in lumbar segments L3-7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7-L7), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A, and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT7 receptor was highest in the L5-L7 segments (>90%) and decreased rostrally (to approximately 50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60-80 and 35-80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5-HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT(7)/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments.

A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model.

This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that could be considered for a clinical trial in time. Minocycline has been shown to have neuroprotective effects in models of central nervous system injury, including in a contusive spinal cord injury (SCI) model at the thoracic level. Beneficial effects of minocycline treatment included a significant improvement in locomotor behavior and reduced histopathological changes [Lee, S.M., Yune, T.Y., Kim, S.J., Park, D.O.W., Lee, Y.K., Kim, Y.C., Oh, Y.J., Markelonis, G.J., Oh, T.H., 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 20, 1017-1027.] To verify these important observations, we repeated this study in our laboratory. The NYU (MASCIS) Impactor was used to produce a moderate cord lesion at the vertebral level T9-T10 (height 12.5 mm, weight 10 g), (n=45), followed by administration of minocycline, 90 mg/kg (group 1: minocycline IP, n=15; group 2: minocycline IV, n=15; group 3: vehicle IP, n=8; group 4: vehicle IV, n=7) immediately after surgery and followed by two more doses of 45 mg/kg/IP at 12 h and 24 h. Open field locomotion (BBB) and subscores were examined up to 6 weeks after SCI and cords were processed for quantitative histopathological analysis. Administration of minocycline after SCI did not lead to significant behavioral or histopathological improvement. Although positive effects with minocycline have been reported in several animal models of injury with different drug administration schemes, the use of minocycline following contusive SCI requires further investigation before clinical trials are implemented.

A re-assessment of erythropoietin as a neuroprotective agent following rat spinal cord compression or contusion injury.

This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that appear promising for eventual clinical testing. We repeated a study reporting the beneficial effects of recombinant human erythropoietin (rhEPO) treatment after spinal cord injury (SCI). Moderate thoracic SCI was produced by two methods: 1) compression due to placement of a modified aneurysm clip (20 g, 10 s) at the T3 spinal segment (n=45) [followed by administration of rhEPO 1000 IU/kg/IP in 1 or 3 doses (treatment groups)] and 2) contusion by means of the MASCIS impactor (n = 42) at spinal T9 (height 12.5 cm, weight 10 g) [followed by the administration of rhEPO 5000 IU/kg/IP for 7d or single dose (treatment groups)]. The use of rhEPO following moderate compressive or contusive injury of the thoracic spinal cord did not improve the locomotor behavior (BBB rating scale). Also, secondary changes (i.e. necrotic changes followed by cavitation) were not significantly improved with rhEPO therapy. With these results, although we cannot conclude that there will be no beneficial effect in different SCI models, we caution researchers that the use of rhEPO requires further investigation before implementing clinical trials.

Tratamiento endoscópico de banda gástrica penetrada / Endoscopic treatment of an extruded gastric band

Se describe el caso de una paciente a quien se le colocó una banda gástrica como tratamiento de su obesidad mórbida con buen resultado en cuanto a pérdida de peso. Presentó extrusión de la banda gástrica al estómago luego de 1 año, y a los 26 meses ya estaba prácticamente en el estómago sostenida por un pequeño puente de tejido. Se realizaron dos procedimientos endoscópicos para extraerla. En el primero se seccionó el puente de tejido pero la banda permaneció fija por el conector que comunica con el reservorio subcutáneo, el cual había sido retirado previamente. En el segundo procedimiento, una semana después del primero, se cortó la banda, ya libre en el estómago, con un litotriptor biliar y una guía monofilamento, logrando luego extraerla con facilidad. Se describen los procedimientos, las dificultades que se tuvieron y cómo se resolvieron

Serotonin concentrations in the lumbosacral spinal cord of the adult rat following microinjection or dorsal surface application.

Application of neuroactive substances, including monoamines, is common in studies examining the spinal mechanisms of sensation and behavior. However, affected regions and time courses of transmitter activity are uncertain. We measured the spatial and temporal distribution of serotonin [5-hydroxytryptamine (5-HT)] in the lumbosacral spinal cord of halothane-anesthetized adult rats, following its intraspinal microinjection or surface application. Carbon fiber microelectrodes (CFMEs) were positioned at various locations in the spinal cord and oxidation currents corresponding to extracellular 5-HT were measured by fast cyclic voltammetry. Intraspinal microinjection of 5-HT (100 microM, 1-3 microl) produced responses that were most pronounced at CFMEs positioned

Programa de detección endoscópica del cáncer gástrico con especial atención a las formas tempranas Estudio en poblaciones de riesgo en Caldas, febrero de 1992 a febrero de 1997 / Endoscopic gastric cancer detection program with especial atention to early stages. A study in the state of Caldas (Colombia) conducted between 1992 and 1997

El cáncer gástrico en Colombia es frecuente con zonas epidemiológicas reconocidas con mayor incidencia. El pronóstico de los pacientes es reservado que tiende a ser muy pobre, ya que cuando consultan por lo general lo hacen en su estadio más avanzado. Estudios previos reconocen al departamento de Caldas como la quinta región del país con mayor frecuencia de esta patología, como lo han comprobado análisis regionales en el tema. En Colombia no existe un programa de detección de esta patología en zonas de riesgo, por lo cual se hace necesario implementar este tipo de acciones en salud con el propósito de mejorar los pronósticos, puesto que si el cáncer es detectado y tratado adecuadamente en sus períodos más tempranos, se puede considerar curable. Entre los años 1992 y 1997, la Fundación para el Diagnóstico del Cáncer Gástrico y las Enfermedades Gastrointestinales, inició un programa de detección de cáncer gástrico por medio de la endoscopia, en un intento de detectarlo en estadios precoces o menos avanzados. Las poblaciones escogidas fueron determinadas por trabajos de investigación realizados en Caldas y definidas como de mayor frecuencia...

Steady-state levels of monoamines in the rat lumbar spinal cord: spatial mapping and the effect of acute spinal cord injury.

Monoamines in the spinal cord are important in the regulation of locomotor rhythms, nociception, and motor reflexes. To gain further insight into the control of these functions, the steady-state extracellular distribution of monoamines was mapped in the anesthetized rat's lumbar spinal cord. The effect of acute spinal cord lesions at sites selected for high resting levels was determined over approximately 1 h to estimate contributions to resting levels from tonic descending activity and to delineate chemical changes that may influence the degree of pathology and recovery after spinal injury. Measurements employed fast cyclic voltammetry with carbon fiber microelectrodes to give high spatial resolution. Monoamine oxidation currents, sampled at equal vertical spacings within each segment, were displayed as contours over the boundaries delineated by histologically reconstructed electrode tracks. Monoamine oxidation currents were found in well defined foci, often confined within a single lamina. Larger currents were typically found in the dorsal or ventral horns and in the lateral aspect of the intermediate zone. Cooling of the low-thoracic spinal cord led to a decrease in the oxidation current (to 71-85% of control) in dorsal and ventral horns. Subsequent low-thoracic transection produced a transient increase in signal in some animals followed by a longer lasting decrease to levels similar to or below that with cooling (to 17-86% of control values). We conclude that descending fibers tonically release high amounts of monoamines in localized regions of the dorsal and ventral horn of the lumbar spinal cord at rest. Lower amounts of monoamines were detected in medial intermediate zone areas, where strong release may be needed for descending activation of locomotor rhythms.

Temporal and spatial profiles of pontine-evoked monoamine release in the rat's spinal cord.

In the spinal cord, the monoamine neurotransmitter norepinephrine, which is released mainly from fibers descending from the dorsal pons, has major modulatory effects on nociception and locomotor rhythms. To map the spatial and temporal patterns of this release, changes in monoamine level were examined in laminae I-VIII of lumbar segments L3-L6 of halothane-anesthetized rats during pontine stimulation. The changes were measured through a carbon fiber microelectrode at 0.5-s intervals by fast cyclic voltammetry, which presently is the method of best spatiotemporal resolution. When different pontine sites were tested with 20-s pulse trains (50-to 200-microA amplitude, 0.5-ms pulse width, and 50-Hz frequency) during measurement in the dorsal horn (lamina IV), the largest consistent increases were produced by the locus ceruleus, although effective pontine sites extended 1.5 mm dorsally and ventral from the locus ceruleus. When the locus ceruleus stimulus was used to map the spinal cord, increased levels were always seen in lamina I and laminae IV-VIII, whereas 50% of sites in laminae II and III showed substantial decreases and the rest showed increases. These increases typically had short latencies [4.5 +/- 0.4 (SE) s] and variable decay times (5-200 s), with peaks occurring during the stimulus train (mean rise-time: 12.0 +/- 0.6 s). The mean peak level was 544 +/- 82 nM as estimated from postexperimental calibration with norepinephrine. Other significant laminar differences included higher mean peak concentrations (805 nM) and rise times (14.9 s) in lamina I and shorter latencies in lamina VI (3.2 s). Peak concentrations were inversely correlated with latency. When stimulation frequency was varied, increases were disproportionately larger with faster frequencies (> or =50 Hz), hence extrajunctional overflow probably contributed most of the signal. We conclude, generally, that pontine noradrenergic control is exerted on widespread spinal laminae with a significant component of paracrine transmission after several seconds of sustained activity. Relatively stronger effects prevail where nociceptive transmission (lamina I) and locomotor rhythm generation (lamina VI) occur.

Reflujo duodenogastroesofágico / Duodenogastroesophagic reflux

El reflujo del contenido duodenal dentro del estómago a través del píloro, es un evento fisiológico normal que ocurre más frecuentemente durante la noche, ejercicio fuerte, períodos de ayuno y postprandiales. Cuando es excesivo, puede ser patológico y asociarse a gastritis, úlcera gástrica, carcinoma gástrico y síndrome de dispepsia ulcerosa o no ulcerosa. El contenido duodenal, también puede refluir hacia el esófago, originando diferentes cambios en la mucosa, desde esofagitis leve, hasta esofagitis severa, esófago de Barrett y adenocarcinoma esofágico. Anteriormente se utilizaban los términos de reflujo biliar y reflujo alcalino para describir este proceso; el cual ha sido cambiado por reflujo duodenogastroesofágico (RDGE), debido a que el contenido duodenal está compuesto por algo más que bilis, como ha sido demostrado en recientes estudios, en los cuales refieren que el término reflujo alcalino es incorrecto, ya que el PH > 7 no se correlaciona con el reflujo del contenido duodenal. Así es que, el término reflujo duodenogastroesofágico es más apropiado para describir la regurgitación patológica del contenido duodenal dentro del estómago y de este hacia el esófago. Este tipo de entidades son altamente patológicas y su manejo médico es por lo general difícil al igual que el diagnóstico. Por lo anterior pretendemos hacer una revisión del tema esperando lograr clarificar muchos aspectos del mismo discutiendo su terapia y manejo quirúrgico

Diagnostico endoscopico vs diagnostico histologico: correlacion en la valoracion de los pacientes con esofagitis por reflujo / Correlation between endoscopic and anatomopathological findings in the diferent grades of esophagitis in the gastroesophageal reflux disease

En la actualidad, existen muy pocos estudios en la literatura medica que nos hablen de la correlacion entre los diagnosticos endoscopicos y los anatomopatologicos, en lo concerniente a los diferentes grados de esofagitis por reflujo gastroesofagico (RGE). Objetivo: Estudiar la correlacion entre la endoscopia digestiva alta y la anatomia patologica para el diagnostico de esofagitis por reflujo gastroesofagico patologico. Materiales y metodos: Como parte del estudio, tomamos a todos los pacientes que se sometieron a endoscopia digestiva alta en Video Medicina Endoscopica VIME y que, en uno de sus diagnosticos, tuvieran el de Esofagitis. En total, se incluyeron en el estudio a 65 pacientes, 32 hombres y 33 mujeres. A todos se les realizo la estadificacion endoscopica de la lesion esofagica por RGE, segun la clasificacion modificada de Savary-Miller (Figura 1). Posteriormente, se procedio a tomar biopsias de las zonas lesionadas para el informe histologico. Luego, procedimos a comparar los informes de biopsia con los de endoscopia. Resultados: Encontramos que 42,8 por ciento de los pacientes diagnosticados como esofagitis grado I en la endoscopia, tenian el mismo estadiaje anatomo-patologico; 60 por ciento de los pacientes con esofagitis grado II tenian dicha correlacion; igualmente, 37,5 por ciento de los pacientes con esofagitis grado III y todos los pacientes con esofagitis grado IV la mostraron (100 por ciento); y, 44,4 por ciento de los inicialmente diagnosticados como esofago de Barret, fueron avalados por el estudio histologico...