A Review: Inflammatory Process in Alzheimer's Disease, Role of Cytokines

Alzheimer's disease (AD) is the most common neurodegenerative disorder to date. Neuropathological hallmarks are β-amyloid (Aβ) plaques and neurofibrillary tangles, but the inflammatory process has a fundamental role in the pathogenesis of AD. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the complement system, as well as cytokines and chemokines. Cytokines play a key role in inflammatory and anti-inflammatory processes in AD. An important factor in the onset of inflammatory process is the overexpression of interleukin (IL)-1, which produces many reactions in a vicious circle that cause dysfunction and neuronal death. Other important cytokines in neuroinflammation are IL-6 and tumor necrosis factor (TNF)-α. By contrast, other cytokines such as IL-1 receptor antagonist (IL-1ra), IL-4, IL-10, and transforming growth factor (TGF)-β can suppress both proinflammatory cytokine production and their action, subsequently protecting the brain. It has been observed in epidemiological studies that treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the risk for developing AD. Unfortunately, clinical trials of NSAIDs in AD patients have not been very fruitful. Proinflammatory responses may be countered through polyphenols. Supplementation of these natural compounds may provide a new therapeutic line of approach to this brain disorder

Robust free-spurious formulation of high order 2.5 dimensional electromagnetic problems by using finite elements

The 3D Finite Elements Method (FEM) is an extensively accepted tool for the analysis and design of microwaves/millimetre circuits and antennas based on the use of complex materials and geometries. Despite the huge memory capacity and computation speed of the current informatics systems, the method still suffers from an expensive computational cost when the domain is 3D. In many practical structures, the knowledge of the behaviour of one field component introduces a symmetry in the formulations that allows to project the physical problem onto a bi-dimensional mesh. The result of the former is a dramatic increase of the speed and ease of handling of such kind of problems, achieving efficient tools for the computer assisted design of many complex structures used in the electrical engineering nowadays. Because nothing is free, this simplification in the computation of the numerical problems is reached after a modification into the formulation and discretization of the model in the sense to introduce the symmetry of the field component into the basis functions. Because we need the three field components, we must divide the basis functions in two sets; one keeps the vector character and is applied to approximate the transversal or meridian component of the electromagnetic field and the other set is used for the longitudinal or azimuthal component. Then, we have to work with two elements, one is vector and the other is scalar. Frequently they are called hybrid elements, or 2.5D elements. This type of problems has been intensively studied by many researchers along the last two decades [1], [2], [3], [4], [5], [6]. However, only lower order basis has been used and, since our knowledge, it has not been developed a theory linking the development of the function spaces for the cited two elements, vector and scalar which make up the hybrid elements. This is especially true when the order of the elements increases, producing the apparition of the frightened spurious modes. Besides of the lack of a robust method to obtain these higher order hybrid elements for the 2.5D problems, we consider that it is worth reviewing these procedures, trying to increase its reliability and robustness. It should be a priority to incorporate the use of higher-order elements to the discretization of 2.5D problems, as the last developments relative to pre and post processors, new and more powerful meshers and solvers. In this way we can develop new numerical tools facing the more complex geometries containing field singularities, diverse materials and multiscale details with curved boundaries that conform the structures that electrical engineers handle nowadays. This work is an extension with some new results of previous presented at [5], [7]. A complete study of the design of conical dielectric core horn antennas, ended by both, convex-plane and double-convex dielectric lens, is carried on, taking advantage of the robust performance of the developed methods

Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Obesity affects large numbers of patients with type 1 diabetes (T1D) across their lifetime, with rates ranging between 2.8% and 37.1%. Patients with T1D and obesity are characterized by the presence of insulin resistance, of high insulin requirements, have a greater cardiometabolic risk and an enhanced risk of developing chronic complications when compared to normal-weight persons with T1D. Dual treatment of obesity and T1D is challenging and no specific guidelines for improving outcomes of both glycemic control and weight management have been established for this population. Nevertheless, although evidence is scarce, a comprehensive approach based on a balanced hypocaloric diet, physical activity and cognitive behavioral therapy by a multidisciplinary team, expert in both obesity and diabetes, remains as the best clinical practice. However, weight loss responses with lifestyle changes alone are limited, so in the "roadmap" of the treatment of obesity in T1D, it will be helpful to include anti-obesity pharmacotherapy despite at present there is a lack of evidence since T1D patients have been excluded from anti-obesity drug clinical trials. In case of severe obesity, bariatric surgery has proven to be of benefit in obtaining a substantial and long-term weight loss and reduction in cardiovascular risk. The near future looks promising with the development of new and more effective anti-obesity treatments and strategies to improve insulin resistance and oxidative stress. Advances in precision medicine may help individualize and optimize the medical management and care of these patients. This review, by gathering current evidence, highlights the need of solid knowledge in all facets of the treatment of patients with obesity and T1D that can only be obtained through high quality well-designed studies

Nested multiplex PCR for identification and detection of human Plasmodium species including Plasmodium knowlesi

Objective: To develop a new technique for diagnosis of Plasmodium knowlesi and at the same time to be able to discriminate among the diverse species of Plasmodium causing human malaria. Methods: In this study the nested multiplex malaria PCR was redesigned, targeting the 18S rRNA gene, to identify the fifth human Plasmodium species, Plasmodium knowlesi, together with the other human Plasmodium (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) by amplified fragment size using only two amplification processes and including an internal reaction control to avoid false negatives. The technique was validated with 91 clinical samples obtained from patients with malaria compatible symptoms. The technique showed high sensitivity (100%) and specificity (96%) when it was compared to the reference method employed for malaria diagnosis in the Instituto de Salud Carlos Ⅲ and a published real-time PCR malaria assay. Conclusions: The technique designed is an economical, sensitive and specific alternative to current diagnosis methods. Furthermore, the method might be tested in knowlesi-malaria endemic areas with a higher number of samples to confirm the quality of the method.This work was supported by AESI-ISCⅢ grant number PI14CⅢ/00014.S

Mesoporous niobium oxide for dehydration of D-xylose into furfural

Se ha demostrado que el óxido de niobio mesoporoso es un catalizador eficaz para la deshidratación de D-xilosa a furfural, alcanzando una conversión del 92% y un rendimiento de furfural 49,3% a 170º C y 90 minutos. La lixiviación de Nb, determinada por ICP-MS, era inferior al 0,5% en peso de la concentración de Nb inicial, confirmando de este modo la estabilidad del catalizador ácido sólido.El furfural posee un gran potencial como molécula plataforma de origen renovable para la síntesis de una alta variedad de compuestos químicos. Se obtiene mediante la deshidratación de pentosas, principalmente a partir de D-xilosa, proceso catalizado por ácidos minerales en fase homogénea. Por tanto, dentro de la química verde y la búsqueda de sostenibilidad de los procesos catalíticos, es necesaria su sustitución por catalizadores sólidos ácidos que sean tolerantes al agua, ya que es el disolvente más utilizado para esta reacción. El óxido de niobio posee propiedades ácidas y es insoluble en agua, pero su superficie específica es muy baja. Por lo tanto, resulta muy interesante la síntesis de un óxido de niobio mesoporoso para emplearlo como catalizador en esta reacción. En este trabajo, se ha sintetizado un Nb2O5 mesoporoso y se ha evaluado su comportamiento catalítico en la obtención de furfural a partir de D-xilosa.Spanish Ministry of Science and Innovation (ENE2009-12743-C04-03 project)Junta de Andalucía (P09-FQM-5070).Ministry of Science and Innovation for the financial support under the Program Ramón y Cajal (RYC-2008-03387)

External match load in amateur soccer: the influence of match location and championship phase

Assessment of the physical dimension implicit in the soccer match is crucial for the improvement and individualization of training load management. This study aims to: (a) describe the external match load at the amateur level, (b) analyze the differences between playing positions, (c) verify whether the home/away matches and if (d) the phase (first or second) of the championship influence the external load. Twenty amateur soccer players (21.5 ± 1.9 years) were monitored using the global positioning system. The external load was assessed in 23 matches, where 13 were part of the first phase of the competition (seven home and six away matches) and the other 10 matches belonged to the second (and final) phase of the championship (five home and five away matches). A total of 173 individual match observations were analyzed. The results showed significant differences between playing positions for all the external load measures (p < 0.001). There were higher values observed in the total distance covered for central defenders (p = 0.037; ES = 0.70) and in high-intensity decelerations for forwards (p = 0.022; ES = 1.77) in home matches than in away matches. There were higher values observed in the total distance (p = 0.026; ES = 0.76), relative distance (p = 0.016; ES = 0.85), and moderate-intensity accelerations (p = 0.008; ES = 0.93) for central defenders, in very high-speed running distance for forwards (p = 0.011; ES = 1.97), and in high-intensity accelerations (p = 0.036; ES = 0.89) and moderate-intensity decelerations (p = 0.006; ES = 1.11) for wide midfielders in the first phase than in the second phase of the championship. Match location and championship phase do not appear to be major contributing factors to influence the external load while the playing position should be used as the major reference for planning the external training load.info:eu-repo/semantics/publishedVersio

An Overview of the Management of Mansonellosis

Mansonellosis is caused by three filarial parasite species from the genus Mansonella that commonly produce chronic human microfilaraemias: M. ozzardi, M. perstans and M. streptocerca. The disease is widespread in Africa, the Caribbean and South and Central America, and although it is typically asymptomatic it has been associated with mild pathologies including leg-chills, joint-pains, headaches, fevers, and corneal lesions. No robust mansonellosis disease burden estimates have yet been made and the impact the disease has on blood bank stocks and the monitoring of other filarial diseases is not thought to be of sufficient public health importance to justify dedicated disease management interventions. Mansonellosis´s Ceratopogonidae and Simuliidae vectors are not targeted by other control programmes and because of their small size and out-door biting habits are unlikely to be affected by interventions targeting other disease vectors like mosquitoes. The ivermectin and mebendazole-based mass drug administration (iMDA and mMDA) treatment regimens deployed by the WHO´s Elimination of Neglected Tropical Diseases (ESPEN) programme and its forerunners have, however, likely impacted significantly on the mansonellosis disease burden, principally by reducing the transmission of M. streptocerca in Africa. The increasingly popular plan of using iMDA to control malaria could also affect M. ozzardi parasite prevalence and transmission in Latin America in the future. However, a potentially far greater mansonellosis disease burden impact is likely to come from shortcourse curative anti-Wolbachia therapeutics, which are presently being developed for onchocerciasis and lymphatic filariasis treatment. Even if the WHO´s ESPEN programme does not choose to deploy these drugs in MDA interventions, they have the potential to dramatically increase the financial and logistical feasibility of effective mansonellosis management.There is, thus, now a fresh and urgent need to better characterise the disease burden and ecoepidemiology of mansonellosis so that effective management programmes can be designed, advocated for and implemented.We would like to express our special thanks to María Belén García Fernández for helping us to draw the life-cycle of Mansonella species. JLC and SLBL also gratefully acknowledge support from the Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM; 062.01282/2018 and 002.00200/2019). And JLC would like to acknowledge support he receives from a Conselho Nacional de Desenvolvimento Científica e Tecnológico (CNPq) productivity grant. THTT is funded by a Sara Borrell contract from the Instituto de Salud Carlos III.S

Tratamiento renal conservador en ancianos con enfermedad renal crónica avanzada

INTRODUCCIÓN: La clasificación por estadios ha permitido dimensionar la Enfermedad Renal Crónica (ERC) como una enfermedad emergente en todo el mundo convirtiéndose en un problema de salud publica. El estudio EPIRCE puso de manifiesto que el 9,1% de la población adulta sufría algún grado de ERC en España con diferencias importantes según la edad. La ERC es más frecuente en ancianos, con comorbilidad cardiovascular (hipertensión, diabetes) así como en pacientes frágiles y en definitiva en el paciente crónico-complejo.La ERC se está convirtiendo en un problema geriátrico y comprender y analizar al paciente desde una perspectiva geriátrica integral, puede ayudarnos en el complejo proceso de toma de decisiones.Aunque la supervivencia global suele ser superior en los pacientes que se dializan frente a los que no, esta ventaja se pierde en los mayores en los pacientes más mayores y con comorbilidad, experimentan un importante carga de síntomas y la calidad de vida relacionada con la salud (CVRS) a menudo es deficiente.Ante las evidentes limitaciones en el tratamiento renal sustitutivo (TRS) de estos pacientes surge en la actualidad un interés creciente por conocer si el Tratamiento Renal Conservador (TRC) es una opción terapéutica válida. El TRC supone un manejo integral que debe incluir: intervenciones para retrasar la progresión de la enfermedad renal y minimizar el riesgo de eventos adversos, toma de decisiones compartida, manejo activo de los síntomas, comunicación detallada, planificación de atención avanzada, soporte psicológico, apoyo social, familiar y espiritual.OBJETIVOS: -Establecer las variables predictivas de mortalidad y la CVRS en los pacientes en TRC.-Analizar la presencia y evolución de los síndromes geriátricos en los pacientes en TRC y en TRS.-Comparar la supervivencia, la CVRS y los síntomas de los pacientes en tratamiento conservador y diálisis.MATERIAL Y MÉTODOS:Se diseñó un estudio de cohortes, prospectivo, analítico de pacientes del Servicio de Nefrología del Hospital Universitario Miguel Servet de Zaragoza. La población a estudio comprendía pacientes incidentes en tratamiento conservador (82 pacientes) y diálisis (37 pacientes) con un reclutamiento desde el día 1 de enero del 2015 hasta el día 1 de mayo del 2017.Se estudiaron variables demográficas, clínicas (entre las que se incluyeron antecedentes de patologías previa y evaluación geriátrica integral), fármacos, variables analíticas y variables dependientes (éxitus, ingresos hospitalarios y visitas a urgencias). El seguimiento concluyó con el fallecimiento del paciente o con la fecha de cierre del estudio el 31 de Diciembre de 2017. Se realizaron visitas programadas a los 0, 12 y 24 meses del seguimiento.RESULTADOS: -La mediana de supervivencia en TRC fue de 26,9 (IC 95% 19,6-34,2) meses. En análisis multivariante, la presencia de evento vascular previo (p= 0,038), la comorbilidad medida por el índice de Charlson (p= 0,005), la albúmina descendida (p-Al analizar el cambio en la comorbilidad y situación funcional desde los 24 meses y el principio del tratamiento, no encontramos diferencias en el grado de carga de enfermedad entre ambos grupos (p 0,53) y observamos una pérdida funcional similar entre los dos tratamientos (p 0,8).-La tasa de mortalidad en los pacientes en TRC fue de 23/1000 pacientes-mes y en TRS 8,7/1000 pacientes-mes. La terapia dialítica se asoció a un 63% menos mortalidad (p= 0,018). Tras ajuste por comorbilidad, situación funcional, nutricional y fragilidad observamos un cambio de más de un 10% en HR, perdiendo significación estadística en la modalidad de tratamiento de diálisis.-Los pacientes con menor comorbilidad, tuvieron mejor supervivencia cuando eran tratados con diálisis que de forma conservadora (media de supervivencia 34,25 meses vs 27,29 meses p=0,007). Sin embargo en los pacientes con mayor comorbilidad no había diferencias significativas entre ambos tratamientos (media de supervivencia 22,37 meses vs 22,90 meses p=0,98).-Los pacientes en TRC tuvieron a los 0 meses (basal) peor función física, pero a lo largo del tratamiento, el cambio en la CVRS fue similar entre los dos grupos.-El síntoma más prevalente e intenso en ambos grupos fue la debilidad (98% en TRC y 97% en TRS). La sintomatología en número e intensidad se mantuvo estable a lo largo del seguimiento en ambas terapias, y no hubo diferencias al comparar los dos grupos de tratamiento. CONCLUSIONES: -Los pacientes ancianos con enfermedad renal crónica avanzada en tratamiento renal conservador tienen una mortalidad homogénea a lo largo del seguimiento del estudio. -Los factores predictivos independientes de mortalidad en tratamiento conservador son la presencia de evento vascular previo, la comorbilidad medida por el índice de Charlson, la albúmina descendida y la elevación de PTH. La calidad de vida de los pacientes en tratamiento conservador se mantiene estable.-Los pacientes en tratamiento conservador presentaron peor situación funcional al inicio del estudio con respecto a los pacientes de diálisis. No obstante, el empeoramiento a lo largo del tiempo fue similar en ambos grupos. El inicio de la terapia renal sustitutiva no evita el deterioro funcional en la población anciana. -La ventaja de la diálisis respecto a la terapia conservadora en términos de supervivencia se reduce considerablemente cuando se ajusta para la presencia de los diferentes síndromes geriátricos analizados. -La comorbilidad medida por el índice de Charlson es predictor independiente de mortalidad. En pacientes ancianos con índice de Charlson mayor de 8 puntos, la diálisis no es beneficiosa. -La calidad de vida física se vio más afectada en los pacientes en tratamiento conservador, no así la calidad de vida mental. No hubo diferencias en la evolución de la calidad de vida relacionada con la salud entre los dos tratamientos a lo largo del estudio. <br /