Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans

Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and β-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (β-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4minutes of phasic β-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic β-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic β-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events

COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis

Objective: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. Patients and methods: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. Results: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. Conclusions: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions

A disk of dust and molecular gas around a high-mass protostar

The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (> 8 x Sun's mass) stars has heretofore remained poorly understood. Recent observational studies suggest that high-mass stars may form in essentially the same way as low-mass stars, namely via an accretion process, instead of via merging of several low-mass (< 8 Msun) stars. However, there is as yet no conclusive evidence. Here, we report the discovery of a flattened disk-like structure observed at submillimeter wavelengths, centered on a massive 15 Msun protostar in the Cepheus-A region. The disk, with a radius of about 330 astronomical units (AU) and a mass of 1 to 8 Msun, is detected in dust continuum as well as in molecular line emission. Its perpendicular orientation to, and spatial coincidence with the central embedded powerful bipolar radio jet, provides the best evidence yet that massive stars form via disk accretion in direct analogy to the formation of low-mass stars

Finding polynomial loop invariants for probabilistic programs

Quantitative loop invariants are an essential element in the verification of probabilistic programs. Recently, multivariate Lagrange interpolation has been applied to synthesizing polynomial invariants. In this paper, we propose an alternative approach. First, we fix a polynomial template as a candidate of a loop invariant. Using Stengle's Positivstellensatz and a transformation to a sum-of-squares problem, we find sufficient conditions on the coefficients. Then, we solve a semidefinite programming feasibility problem to synthesize the loop invariants. If the semidefinite program is unfeasible, we backtrack after increasing the degree of the template. Our approach is semi-complete in the sense that it will always lead us to a feasible solution if one exists and numerical errors are small. Experimental results show the efficiency of our approach.Comment: accompanies an ATVA 2017 submissio

Ontology-based data access to Slegge

We report on our experience in ontology-based data access to the Slegge database at Statoil and share the resources employed in this use case: end-user information needs (in natural language), their translations into SPARQL, the Subsurface Exploration Ontology, the schema of the Slegge database with integrity constraints, and the mappings connecting the ontology and the schema

Aseguramiento de la calidad del software mediante la implementación de integración continua

El presente documento pretende evidenciar de manera clara y concisa las diversas ventajas que presenta la puesta en marcha de un sistema o proceso de integración continua. En el ciclo de vida de desarrollo del software, es frecuente encontrarse con errores de código debido a fallas humanas por más profesional y experimentado que sean los equipos de trabajo. Pero entonces, ¿Cómo podemos disminuir la frecuencia de los errores humanos en la codificación? La respuesta es mediante la integración continua. Pero ¿Y cómo? A través del control de calidad mediante la realización de una serie de ejecuciones de pruebas unitarias validando así que cada entrega o cambio realizado al código fuente funcione correctamente en la aplicación. La integración continua es una práctica habitual en el mundo del desarrollo actual, usada principalmente por equipos de desarrollo que han adoptado metodologías ágiles de trabajo. Básicamente, consiste en un proceso por el cual cualquier pequeña mejora en el software se integra rápidamente con el software que se llevará producción. Cualquier mejora, debidamente probada, es integrada en los repositorios de control de versiones, junto con las mejoras producidas por otros desarrolladores del equipo de trabajo. Es por esta razón que se optó por realizar la monografía, lo que a su vez significó realizar una investigación de las tareas imprescindibles para implementar la integración continua, con el fin de identificar las herramientas fundamentales que posibiliten dicho proceso, además de realizar el correspondiente análisis e implementación para la integración entre dichos instrumentos. Además, se realizaron indagaciones sobre las diferentes formas que existen actualmente para ejecutar el proceso de integración continua y la manera en que las empresas realizan dicho proceso, y a su vez los tipos de soluciones informáticas existentes en la actualidad que satisfacen dicha necesidad

A Novel Frequency Analysis Method for Assessing Kir2.1 and Nav1.5 Currents

Voltage clamping is an important tool for measuring individual currents from an electrically active cell. However, it is difficult to isolate individual currents without pharmacological or voltage inhibition. Herein, we present a technique that involves inserting a noise function into a standard voltage step protocol, which allows one to characterize the unique frequency response of an ion channel at different step potentials. Specifically, we compute the fast Fourier transform for a family of current traces at different step potentials for the inward rectifying potassium channel, Kir2.1, and the channel encoding the cardiac fast sodium current, Nav1.5. Each individual frequency magnitude, as a function of voltage step, is correlated to the peak current produced by each channel. The correlation coefficient vs. frequency relationship reveals that these two channels are associated with some unique frequencies with high absolute correlation. The individual IV relationship can then be recreated using only the unique frequencies with magnitudes of high absolute correlation. Thus, this study demonstrates that ion channels may exhibit unique frequency responses

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Fungal microbiota from rain water and pathogenicity of Fusarium species isolated from atmospheric dust and rainfall dust

In order to determine the presence of Fusarium spp. in atmospheric dust and rainfall dust, samples were collected during September 2007, and July, August, and October 2008. The results reveal the prevalence of airborne Fusarium species coming from the atmosphere of the South East coast of Spain. Five different Fusarium species were isolated from the settling dust: Fusarium oxysporum, F. solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples were obtained during significant rainfall events in January and February 2009. Using the dilution-plate method, 12 fungal genera were identified from these rainwater samples. Specific analyses of the rainwater revealed the presence of three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Piñonet and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were chosen because they are the main herbaceous crops in Almeria province. The results presented in this work indicate strongly that spores or propagules of Fusarium are able to cross the continental barrier carried by winds from the Sahara (Africa) to crop or coastal lands in Europe. Results show differences in the pathogenicity of the isolates tested. Both hosts showed root rot when inoculated with different species of Fusarium, although fresh weight measurements did not bring any information about the pathogenicity. The findings presented above are strong indications that long-distance transmission of Fusarium propagules may occur. Diseases caused by species of Fusarium are common in these areas. They were in the past, and are still today, a problem for greenhouses crops in Almería, and many species have been listed as pathogens on agricultural crops in this region. Saharan air masses dominate the Mediterranean regions. The evidence of long distance dispersal of Fusarium spp. by atmospheric dust and rainwater together with their proved pathogenicity must be taken into account in epidemiological studies