Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Novel dual single sided silicon strip detector chip for radiotherapy verification

A novel dual single sided silicon strip detector (SSSSD) chip was designed to meet clinical requirements in radiotherapy verification. An available design from Micron Semiconductor Ltd. (BB7, 500 µ m thick) was the base of a two-dimensional detector adapted into a special configuration with the aim of uniforming and minimizing foreing materials around the active area (64 × 64 mm2). With this purpose, two independent BB7 SSSSDs were mounted in a perpendicular configuration, separated by a 500 µ m kapton dielectric film with the same dimensions as the silicon wafers, thus minimizing air gaps in between. This new configuration, called the dual SSSSD chip design, was mounted on kapton printed circuit board (PCB). Both silicon wafers were divided into 32 strips, 2 mm width each. The aim of developing this detector was to allow 2D dose measurements, improve spatial resolution and perform radiotherapy treatment verification faster than with a previous prototype. Characteristics and performance of the novel detector are presented

Effects on chlorophyll and carotenoid contents in different grape varieties (Vitis vinifera L.) after nitrogen and elicitor foliar applications to the vineyard

Photosynthetic pigments, including carotenoids are important secondary metabolites, which play a key role in photosynthesis. There is little information about the effects of nitrogen and elicitor applications on chlorophyll and carotenoid concentrations in grapes. The aim of this work was therefore to study the effects of the foliar application of nitrogen sources and elicitors to Tempranillo, Garnacha and Graciano (Vitis vinifera L.) grapevines on chlorophyll and carotenoid contents. The results showed that β-carotene and lutein were the most abundant carotenoids in all the samples, ranging from 1336 and 227 to 7054 and 1382 μg/g, respectively. The applied treatments had greater impact on chlorophyll and carotenoid contents in Tempranillo grapes than in Graciano and Garnacha varieties. The content of chlorophyll was determined by the variety factor, while the concentration of carotenoids was influenced by the interaction of variety and treatment factors, depending on the type of foliar application.EEA MendozaFil: Gutiérrez Gamboa, Gastón. Instituto de Ciencias de la Vid y del Vino. Grupo VIENAP; EspañaFil: Marín San Román, S. Instituto de Ciencias de la Vid y del Vino. Grupo VIENAP; EspañaFil: Jofre, Viviana Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Rubio Bretón, Pilar. Instituto de Ciencias de la Vid y del Vino. Grupo VIENAP; EspañaFil: Pérez Alvarez, Eva Pilar. Instituto de Ciencias de la Vid y del Vino. Grupo VIENAP; EspañaFil: Garde Cerdán, Teresa. Instituto de Ciencias de la Vid y del Vino. Grupo VIENAP; Españ

Pulsational frequencies of the eclipsing delta-Scuti star HD 172189

The eclipsing delta-Scuti star HD 172189 is a probable member of the open cluster IC 4756 and a promising candidate target for the CoRoT mission. The detection of pulsation modes is the first step in the asteroseismological study of the star. Further, the calculation of the orbital parameters of the binary system allows us to make a dynamical determination of the mass of the star, which works as an important constraint to test and calibrate the asteroseismological models. From a detailed frequency analysis of 210 hours of photometric data of HD 172189 obtained from the STEPHI XIII campaign we have identified six pulsation frequencies with a confidence level of 99% and a seventh with a 65% confidence level in the range between 100-300 uHz. In addiction, three eclipses were observed during the campaign, allowing us to improve the determination of the orbital period of the system.Comment: 6 pages, 7 figure

Stress tensor fluctuations in de Sitter spacetime

The two-point function of the stress tensor operator of a quantum field in de Sitter spacetime is calculated for an arbitrary number of dimensions. We assume the field to be in the Bunch-Davies vacuum, and formulate our calculation in terms of de Sitter-invariant bitensors. Explicit results for free minimally coupled scalar fields with arbitrary mass are provided. We find long-range stress tensor correlations for sufficiently light fields (with mass m much smaller than the Hubble scale H), namely, the two-point function decays at large separations like an inverse power of the physical distance with an exponent proportional to m^2/H^2. In contrast, we show that for the massless case it decays at large separations like the fourth power of the physical distance. There is thus a discontinuity in the massless limit. As a byproduct of our work, we present a novel and simple geometric interpretation of de Sitter-invariant bitensors for pairs of points which cannot be connected by geodesics.Comment: 35 pages, 4 figure

Clinical implication of FMR1 intermediate alleles in a Spanish population

FMR1 premutation carriers (55-200 CGGs) are at risk of developing Fragile X-associated primary ovarian insufficiency as well as Fragile X-associated tremor/ataxia syndrome. FMR1 premutation alleles are also associated with a variety of disorders, including psychiatric, developmental, and neurological problems. However, there is a major concern regarding clinical implications of smaller CGG expansions known as intermediate alleles (IA) or gray zone alleles (45-54 CGG). Although several studies have hypothesized that IA may be involved in the etiology of FMR1 premutation associated phenotypes, this association still remains unclear. The aim of this study was to provide new data on the clinical implications of IA. We reviewed a total of 17 011 individuals: 1142 with primary ovarian insufficiency, 478 with movement disorders, 14 006 with neurodevelopmental disorders and 1385 controls. Similar IA frequencies were detected in all the cases and controls (cases 1.20% vs controls 1.39%, P =.427). When comparing the allelic frequencies of IA = 50CGGs, a greater, albeit not statistically significant, number of alleles were detected in all the cohorts of patients. Therefore, IA below 50 CGGs should not be considered as risk factors for FMR1 premutation-associated phenotypes, at least in our population. However, the clinical implication of IA = 50CGGs remains to be further elucidated

Analysis and modeling of CLBG using the transfer matrix

Gratings in optical fibers have been increasingly used in a variety of applications such as sensors and Telecomm. Depending on perturbation separation, they are classified as: fiber Bragg gratings (FBG), and long period gratings (LPG), whose each spectral output offer advantages for certain applications. Nowadays there is a great interest in the study of arrays formed by the combination of long period gratings and Bragg gratings in cascade (CLBG), where the propagation modes of the core and the cladding propagate in the Bragg grating after they propagate in the LPG. In this work, analysis and modeling of Cascaded Long Bragg Gratings using the Transfer Matrix method was performed for the case of two gratings in series along one fiber. We analyzed the variation of the FWHM of the reflectance and transmittance spectra for different values of the difference of the refractive indexes of the core and the perturbation of the grating, using the typical core refractive index of an SMF-28 as reference value. For smaller index difference a narrow intensity peak was observed. After the number of perturbations was varied, when there is a greater number of perturbations in the grating, there is greater intensity in reflectance. However, as our results show, this dependence is not a linear function. The results were obtained under the maximum-reflectivity condition (tuned) for each single grating. The development of the mathematical model, the results of the simulation and the analysis of results are part of the development of the present work11103SPIE Optical engineering + applications - Optical modeling and system alignmentAuthors are grateful to UAM-Azcapotzalco, CONACYT, University of Twente and UNICAMP for their suppor

A Novel Missense Mutation, I890T, in the Pore Region of Cardiac Sodium Channel Causes Brugada Syndrome

Brugada syndrome (BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na+ channel alpha subunit (Nav1.5). The aim of this work was to characterize the functional alterations caused by a novel SCN5A mutation, I890T, and thus establish whether this mutation is associated with BrS. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Wild-type (WT) or I890T Nav1.5 channels were heterologously expressed in human embryonic kidney cells. Sodium currents were studied using standard whole cell patch-clamp protocols and immunodetection experiments were performed using an antibody against human Nav1.5 channel. A marked decrease in current density was observed in cells expressing the I890T channel (from -52.0±6.5 pA/pF, n = 15 to -35.9±3.4 pA/pF, n = 22, at -20 mV, WT and I890T, respectively). Moreover, a positive shift of the activation curve was identified (V1/2 = -32.0±0.3 mV, n = 18, and -27.3±0.3 mV, n = 22, WT and I890T, respectively). No changes between WT and I890T currents were observed in steady-state inactivation, time course of inactivation, slow inactivation or recovery from inactivation parameters. Cell surface protein biotinylation analyses confirmed that Nav1.5 channel membrane expression levels were similar in WT and I890T cells. In summary, our data reveal that the I890T mutation, located within the pore of Nav1.5, causes an evident loss-of-function of the channel. Thus, the BrS phenotype observed in the proband is most likely due to this mutation. © 2013 Tarradas et al

Regulación menstrual en mujeres menores de 20 años

The practice of abortion has accompanied mankind since time immemorial. It is the oldest method known to man to end an unwanted pregnancy. An abortion is the termination of pregnancy in the first 20 weeks or the expulsion of the product of conception that weighs less than 500g. Menstrual regulation has been used for birth control. Among the factors influencing pregnancy in women under 20 years of age it is the non-use of contraception or its failure. Menstrual regulation is more frequent between 14-16 years of age and in those that have no steady partner. The most common causes that motivate pregnancy termination are: continue studying, contraceptive failure, work, marital instability and family problems. It is important to give a warning to the Ministries of Education and Health to promote sexual education in the curriculum at all levels of education to avoid this procedure.La práctica del aborto acompaña a la humanidad desde épocas inmemoriales; el aborto es el método más antiguo conocido por el hombre para terminar un embarazo no deseado y es la interrupción de la gestación en las primeras 20 semanas o la expulsión del producto de la concepción con un peso menor de 500g. La regulación menstrual ha sido utilizada para el control de la natalidad. Entre los factores que influyen en el embarazo en menores de 20 años se encuentra la no utilización de métodos anticonceptivos o su fallo; la regulación menstrual es más frecuente en jóvenes entre 14-16 años que no tienen pareja estable y las causas más frecuentes que motivan la interrupción del embarazo son la continuación de los estudios, el fallo del anticonceptivo, trabajar, la inestabilidad matrimonial y los problemas familiares. Es importante dar un alerta a los Ministerios de Educación y Salud para fomentar la educación sexual como programa de estudio en todos los niveles de enseñanza para evitar este procedimiento