Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face ...and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.
Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. ...HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts.
A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data.
Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45). Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53).
Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.
The purpose of this paper is to report the results of ongoing research on the integration of groups at risk of exclusion, in order to facilitate decision-making processes that allow their ...consideration by social protection mechanisms. The main objectives of the research were to 000construct tools to explore and assess entry to the workforce based on skills training and risk factors. Study participants comprised groups using services in the area provided by Social Action, which included women at risk, people with disabilities, immigrants, ethnic minorities, present and former drug addicts, and other groups such as homeless people. The methodology is qualitative, through ethnographic fieldwork. We conclude that, unlike poverty and marginalisation, which manifest as an economic deficit and thus may be tackled by economic measures, social exclusion corresponds to a social deficit. Exclusion produces deficits in terms of social cohesion, in which factors related to training and the skills acquired play an essential role.
One of the major transformations in religion in contemporary societies has been the decline of church institutions and their reconstruction within a diverse network of associations, therapies, ...markets and other unconventional spiritual services. Based on extensive ethnographic fieldwork on religious behaviours and dynamics in sports contexts, and taking the similarities between sport and religion as the point of departure, this paper analyses, reflects on and theorises about the symbolic affinities of these two contemporary social institutions. The results show that symbolism converges in the religious element, tending to improve aspects related to sports ethics and establishing affective experiences among participants, with positive results for their physical and mental wellbeing. The findings indicate that a symbolic analysis of the various facets of sport is a useful approach for gaining a better understanding of this phenomenon, since besides being biological, diseases are also cultural and social, and thus, disease, religion and ritual are emotionally related.
Multiple Sclerosis (MS) is a progressive disease leading to increasing disability and costs. A literature review was carried out to identify MS costs and to estimate its economic burden in Spain. ...Areas Covered: The public electronic databases PubMed, ScienceDirect and IBECS were consulted and a manual review of communications presented at related congresses was carried out. A total of 225 references were obtained, of which 43 were finally included in the study. Expert Commentary: Three major cost groups were identified: direct healthcare costs, direct non-healthcare costs and indirect costs. There is a direct relationship between disease progression and increased costs, mainly direct non-healthcare costs (greater need for informal care) and indirect costs (greater loss of productivity). The total cost associated with MS in Spain is €1,395 million per year, and that the mean annual cost per patient is €30,050. Beyond costs, a large impact on the quality of life of patients, with an annual loss of up to 13,000 quality-adjusted life years was also estimated. MS has a large economic impact on Spanish society and a significant impact on the quality of life of patients.
•Autocorrelation coefficients based on the parameters of a Hidden Markov Model.•Received Signal Strength Indicator modeling using a Hidden Markov Model.•Hidden Markov Models can deal with absent ...signal values.•Comparison between models based on mixture of Gaussians and a Hidden Markov Model.
Wi-Fi fingerprinting is one of the methods that are widely used to provide Location Based Services (LBS). Gaussian, or a mixture of Gaussians, is the preferred model used by Wi-Fi fingerprinting for LBS. Nevertheless, Received Signal Strength Intensity (RSSI) Wi-Fi histograms are skewed, and a Gaussian model is not well suited for modeling data when their histogram is skewed. In addition, another important characteristic present in the RSSI Wi-Fi temporal series is autocorrelation, which cannot be modeled using a Gaussian model. In this paper, we explore the feasibility of using Hidden Markov Models (HMM) to model RSSI Wi-Fi signals. The mathematical derivation of formulas to calculate autocorrelation based on the HMM parameters is presented. Exhaustive experimentation, using data sampled in a real scenario, was performed to test the dependency of the autocorrelation coefficients on the number of hidden states, and the number of iterations used when creating the HMM. The results are compared with autocorrelation coefficients calculated using the real data. Kullback–Leibler (KL) divergence was used to compare the similarity of the real histograms and those provided by a mixture of Gaussians and by an HMM. HMM models reported more accurate results than a mixture of Gaussians model in both cases.
El artículo se enmarca en la discusión sobre los problemas de la reforma de las
empresas estatales en las economías centralmente planificadas, específicamente
en el caso de Cuba. Algunos de los ...mayores obstáculos para que las empresas
mejoren su desempeño y cumplan con su rol en el sistema económico se relacionan
con la multiplicidad de objetivos que se les impone centralmente y el ejercicio
de funciones monetarias y fiscales ajenas a estas entidades. Para solucionarlo
se proponen ideas para una hoja de ruta que comienza por una nueva clasificación
de las empresas estatales cubanas a partir de considerar una función de
optimización diferente. No obstante, se apunta que el éxito de esta propuesta
depende de otras reformas estructurales acompañantes.
This paper addresses the reform of state-owned enterprises in centrally planned
economies, specifically the case of Cuba. Some of the major obstacles that
hinder restructuring to improve firm performance and the fulfilling of their
role in the economic system have to do with the fact that those entities are
commanded to play monetary and fiscal functions that go well beyond the role of
enterprises in economic systems. This paper proposes first ideas for a road map
starting with a new way to classify Cuban state companies through their
optimisation function. However, the success of such transformation is contingent
on other accompanying structural reforms.
In response to DNA damage, cells activate a phosphorylation-based signaling cascade known as the DNA damage response (DDR). One of the main outcomes of DDR activation is inhibition of ...cyclin-dependent kinase (Cdk) activity to restrain cell cycle progression until lesions are healed. Recent studies have revealed a reverse connection by which Cdk activity modulates processing of DNA break ends and DDR activation. However, the specific contribution of individual Cdks to this process remains poorly understood. To address this issue, we have examined the DDR in murine cells carrying a defined set of Cdks. Our results reveal that genome maintenance programs of postreplicative cells, including DDR, are regulated by the overall level of Cdk activity and not by specific Cdks.
In this article we develop a quantization procedure for Chaplygin Hamiltonizable nonholonomic systems-mechanical systems subject to non-integrable velocity constraints whose reduced mechanics is ...Hamiltonian after a suitable time reparametrization-using Poincaré transformations and geometric quantization. We illustrate the theory developed through examples and discuss potential applications to the study of the quantum mechanics of nanovehicles.
From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment-resistant multiple sclerosis (MS) spasticity, data from ...daily practice have been collected through various projects.
A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.
The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4 sprays/day. No new safety concerns were identified, and adverse events of special interest for a cannabis-based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved 207 patients from 13 specialized MS centres who had been prescribed THC:CBD oromucosal spray. The findings aligned closely with the UK/German/Swiss registry data in terms of 1-year continuation rates (64.7%), mean daily dose (6.6 sprays/day) and safety profile, including no evidence of addiction, abuse or misuse.
The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.
PDF
