Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington’s disease, Alzheimer’s disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity

De la regulación emocional y cognitiva a la autorregulación en el primer año de vida

Self-regulation is one of the most important processes during infant development.The aim of this paper is to present an up-date review of the processes that integrate emotional and cognitive regulation to anlagen of selfregulation in the first year of life, its neuroanatomic basis, and its relationship with possible behavioral outcomes. Self-regulation involves intrinsic and extrinsic mechanisms whose antecedents begin during gestation and in birth are revealed as autonomic inhibition that accompanies sensorial-motor maturation which in turn favors attention. Later on, inhibition with cognitive features that allows the infant to establish adaptive strategies and strengthen its emotional and cognitive regulation will appear. All of the afore mentioned mechanisms promote inhibition that comprises the first and incipient manifestations of executive functions and effortful control, processes that are of primary importance for the development of self-regulation. The anatomical structures involved in self-regulation development are the brain stem, limbic system, and prefrontal cortex. Research leading to the establishment of biomarkers that allow precocious identification of alterations in the afore mentioned systems from theneonatal stage on is lacking. Self-regulation anlagen during the first year of life could be an early marker of future behavioral and cognitive alterations. Nevertheless self-regulation should not be considered the only causal factor. Knowledge of the development of self-regulation could contribute to establish the foundations for preventive and intervention programs at an early age.Uno de los procesos más importantes en el desarrollo del niño es la autorregulación. El objetivo del artículo es realizar una revisión actualizada sobre los procesos que se integran durante el desarrollo de la autorregulación, sus bases neuroanatómicas y su vinculación con posibles desenlaces conductuales.La autorregulación involucra procesos intrínsecos y extrínsecos en un marco socioeconómico y sociocultural, cuyos antecedentes inician durante la gestación y en el nacimiento se manifiestan en una inhibición autonómica que acompaña la maduración sensorio-motora y favorece la atención. Posteriormente, aparece una inhibición con rasgos cognitivos que permite al bebé establecer estrategias adaptativas y fortalecer su regulación emocional y cognitiva, esto promueve una inhibición que constituye las primeras e incipientes manifestaciones de las funciones ejecutivas y del esfuerzo de control, procesos primordiales para el desarrollo de la autorregulación. Las estructuras neuroanatómicas involucradas en el desarrollode la autorregulación son tallo cerebral, sistema límbico y corteza prefrontal. Falta investigación encaminada a establecer biomarcadores que permitan identificar precozmente alteraciones en dichos sistemas desde la etapa neonatal. Los esbozos de la autorregulación en el primer año de vida apuntan a ser unmarcador temprano de futuras alteraciones conductuales y cognitivas, aunque laautorregulación no debe considerarse el factor causal único. Los conocimientosdel desarrollo de la autorregulación podrán contribuir a establecer los fundamentosde programas de prevención e intervención en edades tempranas

Comparative Efficacy of Botulinum Toxin in Salivary Glands vs. Oromotor Therapy in the Management of Sialorrhea in Cerebral Palsy Impact on Sleep Quality

AimsThe aim of this study was to compare the effects of intraglandular abobotuliniumtoxinA application and oromotor therapy in the management of sialorrhea in patients with cerebral palsy and its effect on sleep quality.MethodsA comparative study (n = 134), mean age 7.1 years (± 3.9 years) was performed in pediatric patients, between the efficacy of abobotuliniumtoxinA in salivary glands and oromotor therapy (JT), with a control group receiving exclusive oromotor therapy (EOMT). Demographic variables, as well as Gross Motor Function Classification System (GMFCS), Drooling Severity and Frequency Scale (DSFS), Sleep Disturbance Scale for Children (SDSC) and Eating and Drinking Ability Classification System (EDACS) were analyzed in 134 patients considering two measurements 6 months apart. Statistical analysis was developed between both groups.ResultsThe greatest improvement in safety and efficacy of swallowing were those in the JT group with initial levels of EDACS IV and V. Both therapies result in favorable changes of all subscales means of SDSC, with joint therapy showing the greater benefit (p = 0.003) over EOMT (p = 0.06), especially for Sleep Breathing Disorders and Disorders of initiating and maintaining sleep (p < 0.01 vs. p = 0.07). No major adverse effects were found, only those expected from the application of the toxin, such as pain, mild, and transient local inflammation.InterpretationA correlation between frequency and intensity of sialorrhea, with the frequency of sleep disorders and dysphagia was found. Conventional EOMT proved to be useful, improving the safety and efficacy of swallowing, sialorrhea and sleep disorder, however it can be enhanced with the application of abobotuliniumtoxinA

Preparation and Characterization of Kynurenic Acid Occluded in Sol-Gel Silica and SBA-15 Silica as Release Reservoirs

Kynurenic acid (KYNA) may have important therapeutic effects in neurological disorders; however, its use as a neuroprotective agent is restricted due to its very limited ability to cross the blood brain barrier (BBB). For this reason, we are looking for new alternatives for KYNA to reach the brain; one of them is using drug delivery systems. To obtain KYNA release reservoirs, KYNA molecules were hosted in two different silica materials. The different KYNA-silica materials were characterized by means of several physical techniques. The spectroscopic studies showed that KYNA molecules remained unchanged once hosted in silica materials. The surface area values of KYNA-silica samples were substantially lower than those for pure silica materials due to the addition of the drug. The electronic micrographs showed that the sol-gel KYNA-silica material consisted of aggregates of nanoparticles around 50 nm in size. On the other hand, the typical SBA-15 hexagonal arrangement was observed, even when hosting KYNA molecules. KYNA release profiles, carried out during approximately 300 hours, showed a first stage of fast drug release followed by a slow release phase. The experimental values fitted to the Peppas equation indicate that the release mechanism was controlled by Fickian diffusion

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

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Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

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