The Glutamatergic System in Primary Somatosensory Neurons and Its Involvement in Sensory Input-Dependent Plasticity.

Glutamate is the most common neurotransmitter in both the central and the peripheral nervous system. Glutamate is present in all types of neurons in sensory ganglia, and is released not only from their peripheral and central axon terminals but also from their cell bodies. Consistently, these neurons express ionotropic and metabotropic receptors, as well as other molecules involved in the synthesis, transport and release of the neurotransmitter. Primary sensory neurons are the first neurons in the sensory channels, which receive information from the periphery, and are thus key players in the sensory transduction and in the transmission of this information to higher centers in the pathway. These neurons are tightly enclosed by satellite glial cells, which also express several ionotropic and metabotropic glutamate receptors, and display increases in intracellular calcium accompanying the release of glutamate. One of the main interests in our group has been the study of the implication of the peripheral nervous system in sensory-dependent plasticity. Recently, we have provided novel evidence in favor of morphological changes in first- and second-order neurons of the trigeminal system after sustained alterations of the sensory input. Moreover, these anatomical changes are paralleled by several molecular changes, among which those related to glutamatergic neurotransmission are particularly relevant. In this review, we will describe the state of the art of the glutamatergic system in sensory ganglia and its involvement in input-dependent plasticity, a fundamental ground for advancing our knowledge of the neural mechanisms of learning and adaptation, reaction to injury, and chronic pain.

Outcome of mild cognitive impairment comparing early memory profiles.

BACKGROUND: : Finding variables that predict decline or stability in persons with amnestic mild cognitive impairment (aMCI) is an important step in identifying subjects in prodromal stages of dementia. This study tests a clinical observation suggesting that aMCI cases with better-preserved recognition skills, despite similar delayed recall deficits, are more likely to remain functionally stable. METHODS: : A cohort of 210 cases with aMCI, diagnosed with standardized criteria that had been followed up for 48 ± 12 months (range: 36-100), were divided into two groups according to their initial recognition memory discrimination index (DI) on the Hopkins Verbal Learning Test (DI ≥ or <8). We compared the two groups according to demographic and neuropsychological variables, cerebral small vessel disease, and outcome (progression to dementia versus stability as aMCI). RESULTS: : Thirty-seven percent progressed to dementia. In the group with the higher DI scores (n = 107), only 21.5% of the cases converted, compared with 52.4% of lower scorers (n = 103; Fisher's test: p < 0.0001). Progression to dementia occurred significantly later in cases with higher DI (50 ± 17 versus 26 ± 11 months in cases with impaired DI, Mann-Whitney test, U statistic = 1092.5, p < 0.0001). The group with lower DI showed a threefold-increased rate of progression to dementia. A multivariate regression model revealed DI, delayed recall, age, and family history of dementia as the strongest predictors of dementia, in this order. CONCLUSIONS: : The aMCI patients with better-preserved recognition at baseline have a more benign prognosis. Detection of these cases may aid in isolating other aMCI cases that are already in prodromal stages of AD and in selecting more homogeneous groups for clinical trials.

Changes in the axon terminals of primary afferents from a single vibrissa in the rat trigeminal nuclei after active touch deprivation or exposure to an enriched environment.

Lasting modifications of sensory input induce structural and functional changes in the brain, but the involvement of primary sensory neurons in this plasticity has been practically ignored. Here, we examine qualitatively and quantitatively the central axonal terminations of a population of trigeminal ganglion neurons, whose peripheral axons innervate a single mystacial vibrissa. Vibrissa follicles are heavily innervated by myelinated and unmyelinated fibers that exit the follicle mainly through a single deep vibrissal nerve. We made intraneural injections of a mixture of cholera-toxin B (CTB) and isolectin B4, tracers for myelinated and unmyelinated fibers, respectively, in three groups of young adult rats: controls, animals subjected to chronic haptic touch deprivation by unilateral whisker trimming, and rats exposed for 2 months to environmental enrichment. The regional and laminar pattern of terminal arborizations in the trigeminal nuclei of the brain stem did not show gross changes after sensory input modification. However, there were significant and widespread increases in the number and size of CTB-labeled varicosities in the enriched condition, and a prominent expansion in both parameters in laminae III-IV of the caudal division of the spinal nucleus in the whisker trimming condition. No obvious changes were detected in IB4-labeled terminals in laminae I-II. These results show that a prolonged exposure to changes in sensory input without any neural damage is capable of inducing structural changes in terminals of primary afferents in mature animals, and highlight the importance of peripheral structures as the presumed earliest players in sensory experience-dependent plasticity.

Sensory Input-Dependent Changes in Glutamatergic Neurotransmission- Related Genes and Proteins in the Adult Rat Trigeminal Ganglion.

Experience-dependent plasticity induces lasting changes in the structure of synapses, dendrites, and axons at both molecular and anatomical levels. Whilst relatively well studied in the cortex, little is known about the molecular changes underlying experience-dependent plasticity at peripheral levels of the sensory pathways. Given the importance of glutamatergic neurotransmission in the somatosensory system and its involvement in plasticity, in the present study, we investigated gene and protein expression of glutamate receptor subunits and associated molecules in the trigeminal ganglion (TG) of young adult rats. Microarray analysis of naïve rat TG revealed significant differences in the expression of genes, coding for various glutamate receptor subunits and proteins involved in clustering and stabilization of AMPA receptors, between left and right ganglion. Long-term exposure to sensory-enriched environment increased this left-right asymmetry in gene expression. Conversely, unilateral whisker trimming on the right side almost eliminated the mentioned asymmetries. The above manipulations also induced side-specific changes in the protein levels of glutamate receptor subunits. Our results show that sustained changes in sensory input induce modifications in glutamatergic transmission-related gene expression in the TG, thus supporting a role for this early sensory-processing node in experience-dependent plasticity.

Cathepsin D in a murine model of frontotemporal dementia with Parkinsonism-linked to chromosome 17.

Tauopathies, such as Alzheimer's disease (AD) and Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), are characterized by tau accumulation. This accumulation could result from alterations in tau degradation by either the ubiquitin-proteasome system or the autophagy-lysosomal pathway. To analyze a possible alteration of the autophagy-lysosomal pathway in transgenic mice expressing human tau with three FTDP-17 missense mutations (TauVLW mice), we studied the lysosomal enzyme Cathepsin D. The hippocampi of TauVLW mice, where the human mutant tau accumulates, showed both increased Cathepsin D and partial colocalization of Cathepsin D with human mutant tau. At the ultrastructural level, some multivesicular bodies showed human mutant tau-immunopositive vesicles. This finding could provide insights into the molecular mechanisms of tau degradation in human tauopathies.

Diagnostic capacity of non-echo planar diffusion-weighted MRI in the detection of primary and recurrent cholesteatoma.

INTRODUCTION AND AIMS: the aim of this study was to determine the certainty of non-echo-planar imaging diffusion-weighted magnetic resonance imaging (non-EPI DW MRI) in the diagnosis of primary and recurrent cholesteatoma in patients with clinical suspicion of cholesteatoma, assessing the sensitivity and specificity of the test in both groups. METHODS: Seventy-five patients with clinical suspicion of cholesteatoma were included in our study. Forty-eight cases had primary suspicion of cholesteatoma and 27 cases had recurrent suspicion of cholesteatoma. All patients received non-EPI DW MRI tests before surgery, and radiological and surgical findings were compared. RESULTS: Sensitivity, specificity and the positive and negative predictive value for primary diagnosis of cholesteatoma group were 91.2%, 50%, 81.6% and 70%, respectively. For the recurrent cholesteatoma group these results were 100%, 66.7%, 90.9% and 100%, respectively. CONCLUSION: Non-echo-planar imaging diffusion-weighted magnetic resonance imaging is a high sensitivity imaging test for detecting cholesteatoma, for both primary diagnosis and for recurrent cases.

[Knowledge about dengue and cardio-cerebrovascular disease in a town in Colombia]. / Conocimientos sobre el dengue y las enfermedades cardio-cerebro-vasculares en un municipio de Colombia.

OBJECTIVE: This study aimed at describing a low-income population's knowledge and perception concerning dengue and cardio-cerebrovascular disease in a town in Colombia. METHOD: The study involved qualitative research; data from 16 semi-structured individual and 3 focus groups was collected through questionnaires addressing 3 low-income sectors and then interpreted. Deductive categorisation of data was based on the questions and inductive analysis to establish such population's knowledge for studying their perceptions regarding dengue and cardio-cerebrovascular disease. RESULTS: It was evident that the target population knew about the agents, the forms of acquiring such diseases, the risk factors and action to be taken for preventing and controlling both diseases; however, such knowledge did not represent (i.e. had not led to) changes in their daily practice or lifestyles. CONCLUSIONS: Local health centre actions needs to be supported by theory or models and must go beyond single interventions based essentially on the transmission of information.

Apreciaciones de trabajadores de la salud sobre la implementación del sistema de seguridad en la utilización de medicamentos / Assessments of health workers on the implementation of the safety system in the use of medications

Resumen Introducción: Los errores en la medicación es uno de los eventos adversos más frecuentes en la mayoría de los países de América Latina, lo que ha llevado a promover un sistema para su identificación y reducción en las instituciones de salud. Objetivo: Determinar las apreciaciones del personal de la salud sobre el grado de implementación del sistema de seguridad del paciente en la utilización de medicamentos. Materiales y métodos: Estudio cuantitativo descriptivo en una población de 73 trabajadores de la salud. Se diseñó una encuesta a partir de dos instrumentos: el cuestionario de autoevaluación de la seguridad del sistema de utilización de los medicamentos en los hospitales y el cuestionario sobre seguridad de los pacientes: versión española del Hospital del Ministerio de Sanidad y Consumo y se contrastaron con los lineamientos de la política de seguridad del paciente para Colombia. Las respuestas se midieron mediante un baremo con cuatro categorías: cumple, cumple medianamente, no cumple y no sabe. Resultados: El porcentaje promedio de personas que manifestaron un total cumplimiento en la aplicación de la política fue de 65,1% en la estandarización, almacenamiento y distribución de los medicamentos, 61,7% en su prescripción y 65,5% en su administración y registro. Conclusiones: Se evidenció que aproximadamente la mitad de los encuestados apreciaban falta de cumplimiento en la implementación del sistema de seguridad del paciente que enmarca los procesos de utilización de medicamentos en todas sus etapas. Lo anterior deja ver que, si bien existe teóricamente un sistema de seguridad en la medicación de los pacientes en las instituciones estudiadas, es necesario que se fortalezcan las acciones gerenciales tendientes a garantizar su aplicación efectiva con todos los actores implicados, siendo la vigilancia permanente de los procesos un pilar fundamental.

Abstract Introduction: Errors in medication is one of the most frequent adverse events in most of the countries in Latin America, which has led to promote a system for its identification and reduction in health institutions. Objective: To determine the assessments of health personnel on the degree of implementation of the system of patient safety in the use of medicines. Materials and methods: A quantitative descriptive study with a population of 73 health workers was conducted. A survey was designed based on two instruments: the self-assessment questionnaire for the security of the system for the use of medicines in hospitals and the questionnaire on patient safety: Spanish version of the Hospital of the Ministry of Health and Consumption, and they were contrasted with the guidelines of the patient security policy for Colombia. The answers were measured by a scale with four categories: strongly agree, agree, disagree and do not know. Results: The average percentage of people who indicated a total compliance in the implementation of the policy in the standardization was of 65.1%, storage and distribution of medicines in its prescription 61.7%, and 65.5% in its administration and registration. Conclusions: It was evidenced that approximately half the respondents appreciated lack of compliance in the implementation of the system of patient safety that frames the processes of drug use in all its stages. The foregoing reveals that while there is a security system in the patients' medication in the institutions studied in theory, there is a need to strengthen the management actions aimed at ensuring its effective implementation with all actors involved, being the permanent monitoring of the processes a fundamental pillar.

Modic changes and associated features in Southern European chronic low back pain patients.

BACKGROUND CONTEXT: Conflicting reports exist regarding the prevalence of Modic changes among low back pain (LBP) patients and factors associated with their existence. PURPOSE: To assess the prevalence of Modic changes and other findings on lumbar magnetic resonance imaging (MRI) among Spanish adult chronic LBP patients and the patient characteristics and radiological findings associated with Modic changes. STUDY DESIGN: A cross-sectional imaging study among chronic LBP patients. PATIENT SAMPLE: Four hundred eighty-seven patients (263 women and 224 men) undergoing lumbar spine MRI examination for chronic LBP. OUTCOME MEASURES: Gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, and image features (disc degeneration, type and extension of Modic changes, disc contour, annular tears, spinal stenosis, and spondylolisthesis). METHODS: Ten radiologists from six hospitals across six cities in Spain consecutively recruited adult patients in whom lumbar MRI had been prescribed for LBP lasting ≥3 months. Patients' characteristics and imaging findings were assessed through previously validated instruments. A multivariate logistic regression model was developed to assess the features associated with Modic changes. RESULTS: Modic changes were found in 81% of the patients. The most common was Type II (51.3%), affecting only the end plate. Variables associated with Type I changes were disc contour abnormalities, spondylolisthesis, and disc degeneration. The same variables were associated with a higher risk of Type II or any type of Modic changes, as well as being male, and having a higher BMI. CONCLUSIONS: Modic changes are found in 81% (95% confidence interval, 77-85) of adult Spanish patients in whom an MRI is prescribed for chronic LBP. Modic changes are more likely to be found in males with a high BMI, who also show disc contour abnormalities, spondylolisthesis, or disc degeneration.

Caracterización de los pacientes con diagnóstico de sepsis en una institución de tercer nivel del municipio de Pereira / Characterization of patients with sepsis in a tertiary institution in the municipality of Pereira

Objetivo: Caracterizar los pacientes con diagnóstico de septicemia ingresados al HospitalUniversitario San Jorge de la ciudad de Pereira durante el 2008, remitidos desde la Empresa Socialdel Estado Salud Pereira. Metodología: Se realizó una investigación descriptiva, siendo la fuentede datos inicial el Registro Individual de Prestación de Servicios (RIPS) Se diseñó un instrumentopara obtener los datos a partir de las historias clínicas, ubicadas en los servicios de hospitalizacióny posteriormente de las historias ubicadas en las instituciones de primer nivel de atención de dondefueron remitidos los pacientes. Resultados: El 47,0% fueron hombres y (53,0%) mujeres y la edadpromedio fue de 54,5 años. El 68,4% murieron durante la hospitalización y 31,6% estaban vivosal egreso. El origen de la sepsis fue en un 63,2% abdominal seguido por el respiratorio (21,1%);2 de los pacientes cuyo origen fue abdominal, el trauma por heridas múltiples de bala fue la causaantecedente y 4 pacientes (21,1%) habían recibido procedimientos invasivos. Fueron frecuentescomorbilidades como: diabetes mellitus, enfermedad pulmonar obstructiva crónica, insuficienciacardiaca congestiva e hipertensión arterial. El promedio de días entre el inicio de los síntomas y laconsulta a una institución de salud fue de 7,2. Conclusiones: Las demoras detectadas, tanto en laidentificación de los problemas por parte del paciente como en la atención por parte de los servicios desalud, deben revisarse para garantizar servicios con oportunidad, condición de la calidad del serviciode importancia en el desarrollo de cuadros agravados de sepsis.

Objective: characterize patients with sepsis diagnosis admitted to the Hospital Universitario San Jorgein the city of Pereira in 2008, sent from the State Social Enterprise “Salud Pereira”. Methodology:descriptive study, being the initial data Individual Registration Service Delivery (RIPS). Aninstrument that yielded the data from medical records, located in the hospital and later of the storiesset in the institutions of primary care where patients were referred. Results: 47.0% were male(53.0%) females and the average age was 54,5 years.68,4% died during hospitalization and 31,6%were alive at discharge. The origin of sepsis was 63,2% followed by abdominal breathing (21,1%), 2patients whose origin was abdominal trauma multiple gunshot wounds was the antecedent cause,and 4 patients (21,1%) had received invasive procedures. Were common comorbidities such asdiabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure and hypertension.The average number of days between onset of symptoms and consultation with a health facility was7.2. Conclusions: delays detected in both the identification of problems by the patient and the carefrom health services, should be reviewed to ensure services in a timely, condition of service qualityimportant in the development of paintings aggravated sepsis.

Proton magnetic resonance spectroscopy and magnetoencephalographic estimation of delta dipole density: a combination of techniques that may contribute to the diagnosis of Alzheimer's disease.

Whole-head magnetoencephalographic recordings were obtained from 10 patients with Alzheimer's disease (AD) and 10 healthy controls in a resting position. Spectroscopic examinations were performed by means of a 1.5-tesla whole-body scanner in the temporoparietal regions of both hemispheres. The relationship between (1)H-MRS-based and magnetoencephalography (MEG)-based measures and their conjoined capability to improve the diagnosis of AD were investigated in this study. Logistic regression analyses were performed. Three separated logistic models were calculated for (1)H-MRS-based metabolites, low-frequency magnetic activity, and the combination of both measures. A combined myoinositol/N-acetyl aspartate (mI/NAA)-delta dipole density (DD) model predicted the diagnosis with 90% sensitivity and 100% specificity. Additionally, the combination of temporoparietal mI/NAA and delta DD values explained the variability of individuals' cognitive status. The results support the notion that a multidisciplinary approach may improve the understanding and diagnosis of AD.