Revisiting Pharmacokinetics and Pharmacogenetics of Methadone in Healthy Volunteers

Methadone acts as a μ opioid agonist, a serotonin and norepinephrine reuptake inhibitor, and a noncompetitive N-methyl-D-aspartate receptor antagonist. These actions altogether are responsible for its efficacy in the management of chronic pain. It is available as a racemic mixture of (R)- and (S)-methadone, both being stereoisomers responsible for its analgesic effect. Methadone elimination occurs mainly through metabolism in the liver by CYP3A4, CYP2B6, and CY2C19 and to a lesser extent by CYP2D6 and in the intestine by CYP3A4. The relative intestinal content of CYP2B6 and CY2C19 is unknown but it seems that CYP2B6 is not present at the intestine. CYP3A4, CYP2B6, and CYP2C19 convert methadone mainly into 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine(EDDP). CYP2B6 and CYP2C19 are stereoselective to S- and R-enantiomer, respectively. The pharmacokinetic study carried out in healthy volunteers by our research group confirmed that MTD undergoes recirculation via gastric secretion and intestinal reabsorption and revealed that the drug is extensively metabolized in the liver but intestinal metabolism is not only relevant but also stereoselective. Polymorphisms of the CYP2B6 and CYP2C19 isoenzymes and their relationship with the pharmacokinetics of MTD were also assessed

Autoimmune Epilepsy: New Development and Future Directions

In recent years, there has been accumulating evidence to support an autoimmune etiology for some patients with drug-resistant seizures, typically in the context of an antibody-mediated encephalopathy; any seizure disorder that may be caused by pathogenic autoantibodies, are an example of autoimmune epilepsy. Autoimmunity is characterized by loss of immune tolerance that causes the destruction of cells and tissues. The largest complex histocompatibility system has had a strong association with autoimmune disease, although certain genes encoding cytokines and co-stimulatory molecules increase genetic susceptibility. In spite of having scientific advances in this research area, the conditions underlying mechanisms are unknown.Goal: this chapter aims to present in synthesized form, the genetic, immunological, and environmental factors role in the autoimmunity to epilepsy, as well as the therapeutic approach that has been used to control seizures, mainly where there is a suspected anti-neuronal-antibodies circulation. Methods: a review of the work achieved during the last years in patients with this condition provides information and experience in the diagnosis and treatment of this epilepsy type. For this, a systematic search of PUBMED is conducted using the search terms “autoimmune and epilepsy, auto antibodies and epilepsy, NMDA and epilepsy, AMPA and epilepsy, and GAD and epilepsy.” The list of identified articles was complemented by additional searches for relevant articles in the reference section of the publications captured by the initial search

Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/β-catenin pathway

We examined the effects of osteocyte secreted factors on myogenesis and muscle function. MLO-Y4 osteocyte-like cell conditioned media (CM) (10%) increased ex vivo soleus muscle contractile force by ∼25%. MLO-Y4 and primary osteocyte CM (1-10%) stimulated myogenic differentiation of C2C12 myoblasts, but 10% osteoblast CMs did not enhance C2C12 cell differentiation. Since WNT3a and WNT1 are secreted by osteocytes, and the expression level of Wnt3a is increased in MLO-Y4 cells by fluid flow shear stress, both were compared, showing WNT3a more potent than WNT1 in inducing myogenesis. Treatment of C2C12 myoblasts with WNT3a at concentrations as low as 0.5ng/mL mirrored the effects of both primary osteocyte and MLO-Y4 CM by inducing nuclear translocation of β-catenin with myogenic differentiation, suggesting that Wnts might be potential factors secreted by osteocytes that signal to muscle cells. Knocking down Wnt3a in MLO-Y4 osteocytes inhibited the effect of CM on C2C12 myogenic differentiation. Sclerostin (100ng/mL) inhibited both the effects of MLO-Y4 CM and WNT3a on C2C12 cell differentiation. RT-PCR array results supported the activation of the Wnt/β-catenin pathway by MLO-Y4 CM and WNT3a. These results were confirmed by qPCR showing up-regulation of myogenic markers and two Wnt/β-catenin downstream genes, Numb and Flh1. We postulated that MLO-Y4 CM/WNT3a could modulate intracellular calcium homeostasis as the trigger mechanism for the enhanced myogenesis and contractile force. MLO-Y4 CM and WNT3a increased caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) of C2C12 myotubes and the expression of genes directly associated with intracellular Ca2+ signaling and homeostasis. Together, these data show that in vitro and ex vivo, osteocytes can stimulate myogenesis and enhance muscle contractile function and suggest that Wnts could be mediators of bone to muscle signaling, likely via modulation of intracellular Ca2+ signaling and the Wnt/ β-Catenin pathway

Prosociality and social responsibility. The case of students of a confessional University in Chile

Prosociality is of greater interest in recent decades due to events that have questioned the socially responsible behavior of decision-makers in various organizations. The objective of this research is to describe statistically significant differences in prosocial attitudes through sociodemographic characteristics among students at a confessional university in Chile. A quan-titative, descriptive, and non-experimental cross-sectional study was carried out. A non-probabilistic convenience sample of stu-dents of the last three years of studies at a confessional uni-versity located in south-central Chile was considered. The short scale of prosocial behavior was used, and a descriptive anal- ysis, exploratory factor analysis, and inferential analysis were performed. Prosocial attitudes are composed of three new di¬mensions, which are grouped according to the variables scale of prosocial behavior: comfort and commitment to others, empathy and detachment, and solidarity and help. Gender and religion stand out as statistically significant variables. Future research should consider a more diverse study group, including both de¬nominational and non-denominational universities. Likewise, it would be convenient to study the stability of prosocial attitudes throughout the life cycles and their relationship with other tran-scendent variables such as personality and self-efficacyLa prosocialidad es de gran interés en las últimas décadas debido a eventos que han cuestionado el comportamiento socialmente responsable de los tomadores de decisiones en diversas organizaciones. El objetivo de esta investigación es describir diferencias estadísticamente significativas en actitudes prosociales a través de características sociodemográficas entre estudiantes de una universidad confesional de Chile. Se realizó un estudio cuantitativo, descriptivo y no experimental de corte transversal. Se consideró una muestra no probabilística de conveniencia de estudiantes de los tres últimos años de carrera de una universidad confesional ubicada en la zona centro-sur de Chile. Se utilizó la escala corta de conducta prosocial y se realizó un análisis descriptivo, un análisis factorial exploratorio y un análisis inferencial. Las actitudes prosociales están compuestas por tres nuevas dimensiones, que se agrupan de acuerdo a las variables de la escala de comportamiento prosocial: comodidad y compromiso con los demás, empatía y desapego, y solidaridad y ayuda. El género y la religión destacan como variables estadísticamente significativas. Futuras investigaciones deberían considerar un grupo de estudio más diverso, incluyendo tanto universidades confesionales como no confesionales. Asimismo, sería conveniente estudiar la estabilidad de las actitudes prosociales a lo largo de los ciclos de vida y su relación con otras variables trascendentes como la personalidad y la autoeficacia.Incluye referencias bibliográfica

Aceptabilidad del ensilaje de la parte aérea de la yuca adicionado con diferentes tipos y cantidades de aditivos en bovinos

The objective of this research was to evaluate the influence of the addition of different types and proportions of byproducts and silage additives to the aerial part of cassava on their acceptability silage at different times, involving the sensory variables, chemical composition and acceptability silage. Experimental design was completely randomized with seven types or proportions of additives and four times silage. Treatments were as a witness, the aerial part of cassava supplemented with 2% molasses, common addition in all treatments; Sil-All® (bacterial inoculant); rice bran (15 and 30% inclusive); ground corn cobs (15 and 30% inclusion) and sugar (3% inclusion). The silages added with tusa were largely accepted by the animals, reflected this in greater number and timing of visits and increased consumption. The silages that included bran were the least accepted. The opening of the silo age did not affect (P>0.05) the study variables. The preference of the animals for the ensiled material compared to silage material not confirmed. The acceptability of the ensiled material was related to some quality variables such as pH, ADF, hemicellulose, fat and DISMS.  l objetivo de esta investigación fue evaluar la influencia de la adición de diferentes tipos y proporciones de subproductos y aditivos al ensilaje de la parte aérea de la yuca sobre su aceptabilidad a diferentes tiempos de ensilado, asociando las variables organolépticas, de composición química y aceptabilidad del ensilaje. Se utilizó un diseño completamente al azar con siete tipos o proporciones de aditivos y cuatro tiempos de ensilado. Los tratamientos fueron: como testigo, la parte aérea de la yuca adicionada con 2% de melaza, adición común en todos los tratamientos; Sil-All® (inoculante bacteriano); salvado de arroz (15 y 30% de inclusión); tusa de maíz molida (15 y 30% de inclusión) y azúcar (3% de inclusión). Los ensilajes adicionados con tusa fueron mayormente aceptados por los animales, reflejado esto en mayor número y tiempo de visitas y un mayor consumo. Los ensilajes que incluyeron salvado fueron los menos aceptados. La edad de abertura del silo no afectó (P>0.05) las variables en estudio. Se confirmó la preferencia de los animales por el material ensilado en comparación al material no ensilado. La aceptabilidad de los materiales ensilados se relacionó con algunas variables de calidad, como pH, FDA, hemicelulosa, grasa y la DISMS

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia; departamento de Boyacá

Dentro de nuestra labor psicosocial vemos como a partir de experiencias constructivas determinadas en cada uno de nuestros entornos, se integran acciones de memoria significativas al incorporar como instrumento crucial la foto voz siendo este la principal narrativa vivencial de diversos tipos de violencias tales como: la exclusión social, el desplazamiento forzado, conflicto armado, guerras, reclutamiento ilícitos y demás hechos de desigualdad entorno a la vulneración de derechos propios de las personas. Siendo esto la principal causa para incidir en la prevención de la violencia, ya que esta se reduce considerablemente al integrar acciones en vinculación para con la educación y la promoción de valores como la tolerancia, el respeto y la resolución pacífica de conflictos. A partir de ello identificamos y abordamos las causas subyacentes de la violencia, al ser el impulso para determinar acciones psicosociales que benefician el tratamiento de las comunidades, familias y personas que han sido vilmente perjudicadas. Con el trabajo interdisciplinar ejercido en la labor psicosocial se busca generar un análisis sustancioso para mitigar los impactos psíquicos, y sociales que con lleva la reflexión dada en el caso de la comisión de la verdad fomentando así la reducción de los efectos negativos asociados con salud mental de las víctimas. Desde el apoyo social y reconociendo las necesidades individuales de cada persona al ser una la labor eficaz que nos permite reducir la sensación de aislamiento y mejorar la resiliencia emocional de las personas afectadas.Within our psychosocial work we see how, based on constructive experiences determined in each of our environments, significant memory actions are integrated by incorporating the photovoice as a crucial instrument, this being the main experiential narrative of various types of violence such as: exclusion social, forced displacement, armed conflict, wars, illegal recruitment and other acts of inequality related to the violation of people's own rights. This being the main cause to influence the prevention of violence, since this is considerably reduced by integrating actions in connection with education and the promotion of values such as tolerance, respect and the peaceful resolution of conflicts. From this we identify and address the underlying causes of violence, as it is the impulse to determine psychosocial actions that benefit the treatment of communities, families and people who have been vilely harmed. With the interdisciplinary work carried out in psychosocial work, the aim is to generate a substantial analysis to mitigate the psychological and social impacts that the reflection given in the case of the truth commission entails, thus promoting the reduction of the negative effects associated with mental health. of the victims. From social support and recognizing the individual needs of each person as it is an effective task that allows us to reduce the feeling of isolation and improve the emotional resilience of the affected people

Resistencia antimicrobiana de Staphylococcus aureus aislados en hemocultivos de un hospital de Villa Clara

Introducción: Staphylococcus aureus ha desarrollado una marcada resistencia a los antimicrobianos. Este germen es responsable de la mayoría de las infecciones, que van desde leves hasta graves. Se encuentra circulando tanto en ambientes hospitalarios como comunitarios.Objetivo: determinar la resistencia antimicrobiana de Staphylococcus aureus aislado en los hemocultivos procesados en el Laboratorio de Microbiología del Hospital General Docente Mártires del 9 de abril durante el 2022.Método: se realizó un estudio observacional descriptivo de corte transversal. El universo estuvo compuesto por los 75 hemocultivos procesados que resultaron positivos a S. aureus durante el año 2022. Se utilizó el análisis estadístico. Las variables estudiadas fueron: sexo, servicio de procedencia y resistencia antimicrobiana; variable evaluada según la disponibilidad de discos antimicrobianos del hospital. Resultados: el sexo femenino predominó con casos 26 casos (53,1 %) con respecto al masculino que presentó 23 casos (46,9 %), el servicio con mayor incidencia fue nefrología con 18 casos (36,7 %), la penicilina resultó el antimicrobiana al que presentó mayor resistencia Staphylococcus aureus con 46 casos (93,9 %); mientras que el cloranfenicol fue el de mejor sensibilidad con un total de 32 casos (65,3 %).Conclusiones: la incidencia de hemocultivos positivos a Staphylococcus aureus en el año 2022 fue baja. La penicilina destacó por su nula efectividad para tratar a esta bacteria, en contraparte el cloranfenicol mostró una elevada eficiencia para tratar las infecciones asociadas a este germen

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE