QT variability unrelated to RR variability during stress testing for identification of coronary artery disease

Stress test electrocardiogram (ECG) analysis is widely used for coronary artery disease (CAD) diagnosis despite its limited accuracy. Alterations in autonomic modulation of cardiac electrical activity have been reported in CAD patients during acute ischemia. We hypothesized that those alterations could be reflected in changes in ventricular repolarization dynamics during stress testing that could be measured through QT interval variability (QTV). However, QTV is largely dependent on RR interval variability (RRV), which might hinder intrinsic ventricular repolarization dynamics. In this study, we investigated whether different markers accounting for low-frequency (LF) oscillations of QTV unrelated to RRV during stress testing could be used to separate patients with and without CAD. Power spectral density of QTV unrelated to RRV was obtained based on time-frequency coherence estimation. Instantaneous LF power of QTV and QTV unrelated to RRV were obtained. LF power of QTV unrelated to RRV normalized by LF power of QTV was also studied. Stress test ECG of 100 patients were analysed. Patients referred to coronary angiography were classified into non-CAD or CAD group. LF oscillations in QTV did not show significant differences between CAD and non-CAD groups. However, LF oscillations in QTV unrelated to RRV were significantly higher in the CAD group as compared with the non-CAD group when measured during the first phases of exercise and last phases of recovery. ROC analysis of these indices revealed area under the curve values ranging from 61 to 73%. Binomial logistic regression analysis revealed LF power of QTV unrelated to RRV, both during the first phase of exercise and last phase of recovery, as independent predictors of CAD. In conclusion, this study highlights the importance of removing the influence of RRV when measuring QTV during stress testing for CAD identification and supports the added value of LF oscillations of QTV unrelated to RRV to diagnose CAD from the first minutes of exercise. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'

Estudio de la variabilidad del intervalo QT no relacionada con la variabilidad del ritmo cardiaco durante prueba de esfuerzo para la identificación de enfermedades en las arterias coronarias

Las enfermedades cardiovasculares representan la principal causa de muerte en países industrializados, siendo la cardiopatía isquémica la causa más frecuente de entre todas ellas. Una detección precoz de estas enfermedades proporciona beneficios al disminuir la morbilidad y mortalidad a las que estas se vinculan, pues el tratamiento temprano se asocia a una mejor respuesta terapéutica y curso de la enfermedad. Un procedimiento común por el que se identifican algunas de estas enfermedades, en particular la cardiopatía isquémica, es el estudio de la actividad eléctrica del corazón a través de electrocardiogramas (ECGs) registrados durante prueba de esfuerzo. Los ECGs facilitan el conocimiento de la existencia y gravedad de una enfermedad cardiaca. Estudios recientes señalan una relación entre las variaciones de la fase cardiaca de repolarización ventricular y la existencia de una cardiopatía isquémica. Siguiendo estas líneas de investigación, el objetivo de este trabajo fin de grado es evaluar la capacidad de un índice de variabilidad de la repolarización ventricular durante prueba de esfuerzo extraído del ECG.Específicamente, el nuevo índice cuantifica la repolarización ventricular a través de la variabilidad del intervalo QT no relacionado con el intervalo RR.Las señales ECG analizadas pertenecen a la base de datos FINCAVAS (Finlandia), que contiene los registros durante prueba de esfuerzo de pacientes de los cuales se conoce si sufren o no enfermedades de las arterias coronarias. Se parte de la hipótesis de que el análisis de la repolarización ventricular a través de la variabilidad de QT no relacionada con el RR puede permitir una mejor identificación de los pacientes con cardiopatía isquémica que los índices derivados del ECG utilizados en la actualidad. Esta variabilidad reflejaría la modulación directa de la repolarización ventricular por parte del sistema nervioso autónomo, excluyendo los efectos indirectos que generan las variaciones en el RR.Uno de los retos de este trabajo es conseguir una delineación robusta de los inicios y finales de las ondas del electrocardiograma, en particular, de las ondas Q y T, ya que los ECGs registrados durante prueba de esfuerzo se ven altamente contaminados por ruido muscular y artefactos de movimiento. Posteriormente, se obtiene la variabilidad de estos intervalos y la descomposición de la variabilidad de QT relacionada y no relacionada con el ritmo cardiaco utilizando un análisis tiempo-frecuencia.Los resultados muestran una relación entre la variabilidad del intervalo QT no relacionada con RR y la presencia de cardiopatía isquémica, mostrando una tendencia a una mayor variabilidad de QT no relacionada con RR en sujetos sin CAD.<br /

A novel mobile application to determine mandibular and tongue laterality discrimination in women with chronic temporomandibular disorder

Chronic pain from temporomandibular disorders (TMDs) is caused by a somatosensory disturbance due to sustained activation of central nervous system nociceptive pathways, which can induce changes in neuroplasticity in the thalamus, basal ganglia and limbic system, as well as disturbances in the somatosensory, prefrontal and orbitofrontal cortex and cognitive impairment. The main objective of this study was to determine the discrimination capacity of mandibular and tongue laterality between women with chronic TMDs and asymptomatic women. This descriptive-comparative study examined 2 groups with a total of 30 women. All participants were between the ages of 23 and 66 years and were assigned to the chronic TMD group or the asymptomatic group according to the inclusion criteria. We employed a mobile application developed specifically for this study to measure the accuracy and reaction time (RT) of mandibular and tongue laterality discrimination. The chronic TMD group had a lower success rate in laterality discrimination (mean mandibular accuracy of 40% and mean tongue accuracy of 67%) than the asymptomatic group (mean mandibular accuracy of 61% and mean tongue accuracy of 90%). These results showed statistically significant differences between the groups for mandibular laterality discrimination (d, 1.14; p<0.01) and tongue laterality discrimination (d, 0.79; p=0.03). The asymptomatic group had faster RTs than the chronic TMD group. The data revealed statistically significant differences for the right mandibular RT (d, 0.89; p=0.02) and right tongue RT (d, 0.83; p=0.03). However, there were no significant differences for left mandibular and left tongue RT. We found that the women with chronic TMDs had a lower success rate and slower RTs in the discrimination of mandibular laterality when compared with the asymptomatic women

Potential contribution of distant sources to airborne Betula pollen levels in Northeastern Iberian Peninsula

Betula (birch) pollen is one of the most important causes of respiratory allergy in Northern and Central Europe. While birch trees are abundant inCentral, Northern, and Eastern Europe,theyare scarce inthe Mediterranean territories, especially in the Iberian Peninsula (IP), where they grow only in the northern regions and as ornamental trees in urban areas. However, the airborne birch pollen patterns in Catalonia (Northeastern IP) show abrupt high concentrations in areas withusually low local influence.The intensity of the derived health problemscan beincreasedbyoutbreaksdue to long-range pollen transport. The present work evaluates the different potential contributions to Catalonia from the main source regions: Pyrenees, Cantabria, and the forests of France and Central Europe. To this end, we computed the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) back trajectories of air masses associated with the main Betula pollen peaks occurring simultaneously over different Catalan monitoring stations, and we studied their provenance over a 15-year period. The Vielha aerobiological station on the northern slopes of the Central Pyrenees was used to identify the dates of the pollen season in the Pyrenean region. In order to better understand the role of the Pyrenees, whichis thenearest of thefourbirch forested regions, weclassifiedthepollenpeaksinthe other Catalan stations into three groups based onthe relationship between the peak andthe pollenseason in thePyrenees. Our analysis of back-trajectory residence time, combined with the associated pollen concentration, reveals that two principal routes other than the Pyrenean forest sustain the northerly fluxes that enter Catalonia and carry significant concentrations of Betula pollen. This study has also allowed quantifying the differentiated contributions of the potential sourcePeer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarObjectius de Desenvolupament Sostenible::15 - Vida d'Ecosistemes TerrestresPostprint (published version

Cellular distribution of the histamine H3 receptor in the basal ganglia : functional modulation of dopamine and glutamate neurotransmission

This is the author's version of a work that was accepted for publication in Basal ganglia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Vol. 3 Núm. 2 (Jul. 2013)Altres ajuts: Red_de_Trastornos_Adictivos/RD06/0001/0015Histamine H3 receptors (H3R) are widely expressed in the brain where they participate in sleep-wake cycle and cognition among other functions. Despite their high expression in some regions of the basal ganglia, their functional role in this forebrain neural network remains unclear. The present findings provide in situ hybridization and immunohistochemical evidence for H3R expression in several neuronal populations of the rat basal ganglia but not in astrocytes (glial fibrillary acidic protein immunoreactive cells). We demonstrate the presence of H3R mRNA and protein in dopaminergic neurons (tyrosine hydroxylase positive) of the ventral tegmental area and substantia nigra. In the dorsal and ventral (nucleus accumbens) striatal complex we show H3R immunoreactivity in cholinergic (choline acetyltransferase immunoreactive) and GABAergic neurons (substance P, proenkephalin or dopamine D1 receptor positive) as well as in corticostriatal terminals (VGLUT1-immunoreactive). Double-labelling experiments in the medial prefrontal cortex show that H3R is expressed in D1R-positive interneurons and VGLUT1-positive corticostriatal output neurons. Our functional experiments confirm that H3R ligands modulate dopamine synthesis and the probability of glutamate release in the striatum from cortico-striatal afferents. The presence of H3R in such different neuronal populations and its involvement in the control of striatal dopaminergic and glutamatergic transmission ascribes a complex role to H3R in the function of the basal ganglia neural network

Aproximación terapéutica a las infecciones por microorganismos multirresistentes.

RESUMEN: La infección nosocomial por microorganismos multirresistentes se asocia en la mayoría de los casos a un retraso en el inicio de un tratamiento adecuado y a un fracaso terapéutico, prolongando la estancia hospitalaria, los costes y la mortalidad. Los microorganismos multirresistentes de mayor importancia clínica son: Staphylococcus aureus resistente a meticilina, Enterococcus resistente a vancomicina, enterobacterias multirresistentes, Pseudomonas aeruginosa y Acinetobacter multirresistente. Entre los factores de riesgo para presentar infecciones por microorganismos multirresistentes destacan el tener una estancia hospitalaria prolongada, el ingreso en unidades de cuidados intensivos, el empleo de antibióticos de amplio espectro y la presencia de dispositivos invasivos. Es de gran importancia la correcta elección de la antibioterapia para el tratamiento de infecciones por microorganismos multirresistentes, pero no son menos importantes algunas actitudes básicas descritas en esta revisión, que pueden evitar que estas infecciones lleguen a producirse, con lo que ahorraremos al paciente riesgo, tiempo de hospitalización y toxicidad farmacológica.ABSTRACT: Nosocomial infection by multiresistant microorganisms is associated with delayed initiation of adequate therapy and therapeutic failure, prolonging hospital stay, cost and mortality. Multiresistant microorganisms with a higher clinically relevance are: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, multiresistant enterobacteria, Pseudomonas aeruginosa and multiresistant Acinetobacter. The risk factors for infection due to multiresistant microorganisms are mainly: to have a prolonged hospital stay, stay in a intensive care unit, the use of broad-spectrum antibiotics and the presence of invasive devices. It is really important the correct choice of antibiotherapy to treat infections by multiresistant microorganisms. However, there are not less important some basic attitudes described in this review, which could prevent that these infections happen, decreasing the patient risk, time of hospitalization and drug toxicity

Uso racional de los antibióticos y multirresistencia. Nuevos antimicrobianos.

RESUMEN: El uso inadecuado de antibióticos es actualmente un problema mundial que requiere la revisión de las políticas sanitarias, dada la repercusión que tiene tanto a nivel individual como social. Es de gran importancia detectar la infección l oantes posible, identificar el foco y el patógeno causal, así como su susceptibilidad antibiótica para establecer un tratamiento antibiótico apropiado. Las resistencias a antibióticos son un problema que va aumentando tanto a nivel comunitario como hospitalario, generando una mayor morbilidad, mortalidad y gastos hospitalarios. Debido a esto en los últimos años se han creado en distintos centros hospitalarios programas de optimización de tratamientos antimicrobianos (PROA). Por otro lado, el aumento de las resistencias ha favorecido un incremento en el desarrollo y posterior comercialización de nuevas moléculas antibióticas frente a los principales microorganismos hospitalarios multirresistentes.ABSTRACT: The bad use of antibiotics is a growing problem in global public health that requires action by all government sectors and society in general. It is very important to detect the infection as soon as possible, identify the source of infection, causative pathogen and its antibiotic susceptibility to establish an appropriate antibiotic treatment. The antibiotic resistance is a problem that is increasing over time at Community and in hospitals, generating an increase in morbidity and mortality. Because of this, years ago, antimicrobial stewardships programs began to be created in different hospitals (called PROA in this document). On the other hand, increased resistance has favored the development and commercialization of new molecules of antibiotics against most of the multiresistant microorganisms

Primer análisis de la cronología obtenida en el sitio Choya 68 (depto. de Capayán, provincia de Catamarca, Argentina)

Choya 68 es un sitio ceremonial, con una estructura monticular y en sus adyacencias amplias superficies preparadas y estructuras de paredes de piedra cuadrangulares y rectangulares. En la excavación se recuperó abundante cerámica del tipo Aguada Portezuelo. En menor proporción Aguada pintado y Aguada negro grabado. Se dan a conocer las edades suministradas por tres laboratorios de C14, para estas estructuras, se efectúan observaciones respecto de la asociación entre las muestras y los eventos arqueológicos respectivos, y se analizan las probables causas de las diferencias interlaboratorios observadas. Se concluye estimando que la variable más importante de las dataciones C14 es la heterogeneidad cronológica de las muestras de carbón analizadas.Facultad de Ciencias Naturales y Muse

Lysosomal lipid alterations caused by glucocerebrosidase deficiency promote lysosomal dysfunction, chaperone-mediated-autophagy deficiency, and alpha-synuclein pathology

Mutations in the GBA gene that encodes the lysosomal enzyme β-glucocerebrosidase (GCase) are a major genetic risk factor for Parkinson's disease (PD). In this study, we generated a set of differentiated and stable human dopaminergic cell lines that express the two most prevalent GBA mutations as well as GBA knockout cell lines as a in vitro disease modeling system to study the relationship between mutant GBA and the abnormal accumulation of α-synuclein. We performed a deep analysis of the consequences triggered by the presence of mutant GBA protein and the loss of GCase activity in different cellular compartments, focusing primarily on the lysosomal compartment, and analyzed in detail the lysosomal activity, composition, and integrity. The loss of GCase activity generates extensive lysosomal dysfunction, promoting the loss of activity of other lysosomal enzymes, affecting lysosomal membrane stability, promoting intralysosomal pH changes, and favoring the intralysosomal accumulation of sphingolipids and cholesterol. These local events, occurring only at a subcellular level, lead to an impairment of autophagy pathways, particularly chaperone-mediated autophagy, the main α-synuclein degradative pathway. The findings of this study highlighted the role of lysosomal function and lipid metabolism in PD and allowed us to describe a molecular mechanism to understand how mutations in GBA can contribute to an abnormal accumulation of different α-synuclein neurotoxic species in PD pathology.The authors wish to thank Dr. Arango (VHIR) for the PX461 vector and all the Vila lab members for their support. This work was supported by the Fondo de Investigación Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER (PI17/00496 and PI20/00728), the Michael J. Fox Foundation, the Silverstein Foundation (MJFF 16182), and the BBVA Foundation (NanoERT). M.M. was supported by an FPU doctoral fellowship (FPU18/05595) from MINECO (Spain); J.R. was supported by a PERIS fellowship (Generalitat de Catalunya); E.P. was supported by a VHIR doctoral fellowship (VHIR, Barcelona).Peer reviewe