Escala de Calgary para el diagnóstico del síncope vasovagal. Estudio de pruebas diagnósticas

ResumenObjetivoEvaluar la utilidad de la escala de Calgary en el diagnóstico de síncope vasovagal comparada con los resultados de la prueba de mesa inclinada (Tilt test) bajo protocolo sensibilizado con medicamentos.MetodologíaEstudio prospectivo de pruebas diagnósticas en pacientes con sospecha de síncope vasovagal sometidos a prueba de mesa inclinada (Tilt test) con vasodilatación inducida con nitroglicerina por vía sublingual. Se incluyeron pacientes mayores de 18 años de edad y se excluyeron pacientes con cardiopatía estructural documentada.ResultadosSe analizaron 100 pacientes, promedio de 48,7 años (DE 19,7), 69% de género femenino y 4% residentes en área rural. La mediana de síncopes al momento del Tilt test fue de 5 (RIQ 2-15) con presentación del primer episodio a los 41 años (RIQ 21-57), en el 52% de los pacientes no se identificaron desencadenantes y las manifestaciones clínicas referidas en los episodios previos al Tilt test fueron diaforesis (58%), palidez (55%), mareo (70%), palpitaciones (50%) y náuseas (42%); durante el Tilt test se reportaron mareo (65%), diaforesis (19%), náuseas (18%) y visión borrosa (18%). Se obtuvo una sensibilidad del 77,7% (IC95%: 66,7-88,8) y una especificidad del 40,5% (IC95%: 23,3-57,7) para la escala de Calgary.ConclusionesDebido a su buena sensibilidad y fácil aplicación, la escala de Calgary es un instrumento útil para el abordaje diagnóstico de pacientes con sospecha de síncope vasovagal y corazón estructuralmente sano, especialmente en menores de 50 años de edad.AbstractObjectiveEvaluate the utility of Calgary score for the diagnosis of vasovagal syncope compared with the results of the Tilt table test using sensibilized protocol with medicines.MethodologyProspective study of diagnostic tests in patients with suspected diagnostic of vasovagal syncope who underwent tilt table test with induced vasodilation with sublingual nitroglycerin. Patients over 18 years were included and patients with documented structural heart disease were excluded.Results100 patients were analyzed, averaging 48.7 years of age (SD 19.7), 69% of feminine genre and 4% residents in rural area. Medium of syncope at the moment of tilt table test was 5 (IQR 2-15), with presentation of first episode at 41 years (IQR 21-57), in 52% of the patients triggers were not identified and the clinical manifestations referred in episodes previous to Tilt test were diaphoresis (58%), pallor (55%), dizziness (70%), palpitations (50%) and nausea (42%); during the test dizziness (65%), diaphoresis (19%), nausea (18%) and blurred vision (18%) were reported. A sensitivity of 77.7% was obtained (95% CI 88.8 66.7) and specificity of 40.5% (95% CI 23.3 - 57.7) for the Calgary score.ConclusionsDue to its high sensitivity and easy application, the Calgary score is a useful diagnostic approach instrument for patients with suspected vasovagal syncope and who have a structurally healthy heart, especially in those younger than 50 years

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Numerical simulation to assess the elastic-strain energy distribution in a silicon rubber disk subjected to a punch shear test (PST)

Finite element method simulations were implemented to understand how the strain energy is distributed in a disk-like sample during a punch shear test. Material’s Young modulus can be estimated from this test; however, there is not enough available information about the distribution of the strain energy inside the sample during the deformation process. The proposed methodology seeks to give insight into the deformation process. Experimental results for a cured silicon rubber sample were used to validate the simulation results. It was found that the estimation of the Young modulus with the punch shear test depends on the ratio between the span-to-punch diameters. This conclusion applies to the simulated results, following Timoshenko’s theory for the deformation of thin plates. Understanding how energy is accumulated during a punch shear test is an important and useful characteristic in terms of the design of armor systems.Simulaciones por el método de elementos finitos fueron empleadas para comprender como se distribuye la energía de deformación al interior de muestras con forma de disco durante un ensayo de punzonado. El módulo de Young puede calcularse a partir de este ensayo; sin embargo, no hay suficiente información disponible sobre la manera en la cual se distribuye la energía de deformación en una muestra durante el proceso de deformación. La metodología propuesta busca dar luces alrededor del proceso de deformación. Resultados experimentales obtenidos con muestras de cauchos siliconados curados fueron usados para validar los resultados de las simulaciones. Se encontró que el valor estimado para del módulo de Young depende de la relación entre el diámetro de la muestra y el diámetro del punzón. Entender como la energía se acumula durante el ensayo de punzonado es un aspecto importante y útil para el diseño de sistemas de protección balística

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (C-11-PiB PET) and structural magnetic resonance imaging (MRI).RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences.DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

Introduction: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). Methods: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11 C-PiB PET) and structural magnetic resonance imaging (MRI). Results: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences. Discussion: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD