Assuntos

RESUMO

Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7-15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene-related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value = 0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value = 0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions.

RESUMO

OBJECTIVE: To evaluate the impact of sustained virologic response (SVR) on liver stiffness, as measured by transient elastography (TE), in Hispanic patients treated with direct-acting antivirals (DAAs) in the outpatient clinics in the Veterans Affairs Caribbean Healthcare System. METHODS: We included hepatitis C virus (HCV) patients treated with DAA regimens from 11/2017 through 06/2019. Patient demographics and variables such as body mass index, HCV genotype, and treatment regimen were collected. The patients had a TE measurement before treatment initiation, and a repeat study 6 to 9 months after the achievement of SVR. A comparison between pre and post-treatment TE scores was performed via a paired t test. RESULTS: Forty-three subjects met all the inclusion criteria and completed a posttreatment TE. Most of the subjects were infected with genotypes 1a or 1b. Six to 9 months post SVR, we measured liver stiffness and found a statistically significant reduction in TE score (P value = .0003). The pretreatment median TE score was 10.2 kPa. On a repeat TE study at 6 to 9 months post-treatment, our subjects had a median score of 7.2 kPa. CONCLUSION: The eradication of HCV infection with DAAs is associated with improved TE scores. Fibrosis-stage reduction was more frequent in those who had stage 4 fibrosis prior to treatment. These results suggest that achieving SVR may spare patients from future clinical decompensation and complications. Adequate screening of this potentially deadly chronic infection can lead to early therapy with DAAs and the significant regression of fibrosis in this kind of patient.

Assuntos

RESUMO

γ-Secretase (GS) is one of the most attractive molecular targets for the treatment of Alzheimer's disease (AD). Its key role in the final step of amyloid-ß peptides generation and its relationship in the cascade of events for disease development have caught the attention of many pharmaceutical groups. Over the past years, different inhibitors and modulators have been evaluated as promising therapeutics against AD. However, despite the great chemical diversity of the reported compounds, a global classification and visual representation of the chemical space for GS inhibitors and modulators remain unavailable. In the present work, we carried out a two-dimensional (2D) chemical space analysis from different classes and subclasses of GS inhibitors and modulators based on their structural similarity. Along with the novel structural information available for GS complexes, our analysis opens the possibility to identify compounds with high molecular similarity, critical to finding new chemical structures through the optimization of existing compounds and relating them with a potential binding site.

Assuntos

RESUMO

We have previously reported the synthesis, in vitro and in silico activities of new GABA analogues as inhibitors of the GABA-AT enzyme from Pseudomonas fluorescens, where the nitrogen atom at the γ-position is embedded in heterocyclic scaffolds. With the goal of finding more potent inhibitors, we now report the synthesis of a new set of GABA analogues with a broader variation of heterocyclic scaffolds at the γ-position such as thiazolidines, methyl-substituted piperidines, morpholine and thiomorpholine and determined their inhibitory potential over the GABA-AT enzyme from Pseudomonas fluorescens. These structural modifications led to compound 9b which showed a 73% inhibition against this enzyme. In vivo studies with PTZ-induced seizures on male CD1 mice show that compound 9b has a neuroprotective effect at a 0.50 mmole/kg dose. A QSAR study was carried out to find the molecular descriptors associated with the structural changes in the GABA scaffold to explain their inhibitory activity against GABA-AT. Employing 3D molecular descriptors allowed us to propose the GABA analogues enantiomeric active form. To evaluate the interaction with Pseudomonas fluorescens and human GABA-AT by molecular docking, the constructions of homology models was carried out. From these calculations, 9b showed a strong interaction with both GABA-AT enzymes in agreement with experimental results and the QSAR model, which indicates that bulky ligands tend to be the better inhibitors especially those with a sulfur atom on their structure.

Assuntos

RESUMO

γ-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system, and a deficiency of GABA is associated with serious neurological disorders. Due to its low lipophilicity, there has been an intensive search for new molecules with increased lipophilicity to cross the blood-brain barrier to raise GABA concentrations. We have designed and evaluated in vitro and in silico some new analogues of GABA, where the nitrogen atom at the γ-position is embedded in heterocyclic scaffolds and determined their inhibitory potential over the GABA-AT enzyme from Pseudomonas fluorescens. These modifications lead to compounds with inhibitory activity as it occurs with compounds 18a and 19a. The construction of Pseudomonas fluorescens and human GABA-AT models were carried out by homology modeling. Docking assays were done for these compounds over the GABA-AT enzyme models where 19a showed a strong interaction with both GABA-AT enzymes.

Assuntos

RESUMO

Este estudio presenta el proceso de desarrollo del Cuestionario de Experiencias de Violencia en las Relaciones de Pareja y Familia en Estudiantes Universitarios, así como sus propiedades psicométricas y hallazgos a través de un estudio piloto. El diseño utilizado fue no experimental, transversal correlacional con una muestra por disponibilidad de 267 estudiantes. En la versión final, el instrumento consta de 41 reactivos y cuatro subescalas: Violencia de la Pareja hacia el Estudiante, Violencia del Estudiante hacia la Pareja, Violencia Observada entre los Padres y Violencia de los Padres hacia el Estudiante. La escala total y las subescalas obtuvieron índices de confiabilidad adecuados. En promedio, la muestra endosó diez experiencias de violencia en diversos contextos. Los hallazgos de este estudio aportan al conocimiento de la prevalencia de la violencia en múltiples contextos, viabilizando el diseño de intervenciones pertinentes en el manejo y prevención de la violencia en poblaciones universitarias.

This study describes the process of developing the Experiences of Violence in Couple and Family Relationships in University Students Questionnaire, its psychometric properties and the results of the pilot study. The research design used for this study was a nonexperimental, transversal co relational design. The nonrandomized sample consisted of 267 students. The final version of the questionnaire consisted of 41 items and four sub-scales which measured experiences with violence in a relationship as an Aggressor and as a Victim, Observed between the Parents and in the Parent-child relationship as a victim. The total scale and the subscales obtained adequate reliability indexes. On average, the sample reported ten experiences with violence in different contexts. The results of this study contribute data on the prevalence of violence in college students' romantic and family relationships which in turn, provide valuable information for planning prevention and early intervention efforts with this population.

RESUMO

Con el objeto de describir los cambios en el metabolismo energético desde un mes antes del parto hasta un mes postparto y su relación con posibles cambios en la condición corporal (CC), se seleccionaron 20 vacas Brahman de la zona del Magdalena Medio, Colombia. A cada vaca se le tomaron 10 mL de sangre mediante Vacutainer® a las cuatro semanas antes del parto y cuatro semanas postparto. La concentración de glucosa, triglicéridos, colesterol total, lipoproteínas de alta densidad (HDL), lipoproteínas de baja densidad (LDL), lipoproteínas de muy baja densidad (VLDL) y CC, fueron evaluadas. Las veinte vacas fueron distribuidas en dos grupos: Grupo 1: ≤ 7 CC y Grupo 2: ≥ 8 CC. Los resultados fueron analizados mediante análisis de varianza y la prueba de Duncan. Se registró un descenso significativo (P<0,05) en los valores de glucosa y altamente significativo (P<0,005) en la fracción lipoprotéica HDL, siendo más notorio en hembras de menor CC; además de un aumento altamente significativo (P<0,005) en las concentraciones de la fracción LDL en las hembras de mayor CC. En los demás parámetros no se apreciaron cambios significativos. Se concluye que las hembras de cría Brahman objeto del estudio sufren un balance energético negativo moderado, que no compromete en mayor grado las reservas energéticas del organismo, debido a los bajos promedios de producción láctea y al adecuado aporte nutricional, notándose mayor dificultad para compensar el déficit energético en las hembras de menor CC.

To describe the changes in the energy metabolism from one month prior to calving up and one month postpartum and its relation with possible body condition changes, twenty Brahman cows were selected from Magdalena Medio, in Colombia. Venous blood samples (10 mL) using Vacutainer® system were taken four weeks prior to calving and four weeks postpartum. Glucose, triglycerides, total cholesterol concentrations, High-density lipoproteins (HDL), Low-density lipoprotein (LDL), Very Low-Density Lipoprotein (VLDL) and body condition (BC) were evaluated. Twenty cows were distributed in two groups (1: ≤ 7 BC and 2: ≥ 8 BC). The results were analyzed using analysis of the variance and Duncan test. It was observed significant reduction (P<0.05) in the glucose values and highly significant (P<0.005) in HDL Lipoprotein fraction more visible in low BC cows. In addition highly significant increase (P<0.005) in LDL fraction concentrations, more visible in High BC cows. In the others parameters no were appreciated significant changes. In conclusion, Brahman cows of this study showed a moderate negative energy balance that doesn’t affect the energy body reserves due to low milk production and adequate nutrition. Brahman cows with loss of body condition during the experimental period (≤ 7) presented more problems to obtain energy balance.

RESUMO

Malpositioning of a permanent pacemaker lead in the left ventricle is rare. Usually, a paced right bundle branch pattern is the initial finding that fosters other confirmatory studies such as chest films and transthoracic echocardiogram. We describe the unusual case of an asymptomatic 83-year-old male patient who was incidentally found with a permanent pacemaker lead placed through the atrial septum into the left ventricle. This patient had contraindications for chronic anticoagulation and was placed on antiplatelet therapy instead. He has been well after three years without evidence of embolic episodes.

Assuntos