Resumen Este articulo propone el desarrollo de un modelo numérico 3D del sistema revestimiento-cemento-formación para evaluar la falla mecánica de tension y de corte del cemento en la interfaz revestimiento-cemento a medida que varían las condiciones de presión y temperatura de la formación y del pozo durante la producción. El modelo numérico, el cual incluye la presión de formación, a diferencia de otros propuestos, fue disenado en etapas bajo una discretización por elementos finitos y validado con modelos analíticos. Los resultados muestran que el incremento de la temperatura de formación aumenta la probabilidad de falla de tensión y de corte en el cemento, mientras el aumento de temperatura del pozo disminuye estas probabilidades. Por otro lado, la disminución de la presión del pozo, reduce la probabilidad de falla de corte y aumenta la de tensión. En el caso de la presión de poro, ocurre lo contrario.

Abstract This paper proposes the development of a 3D numerical model of the casing-cement-formation system to evaluate the mechanical tensile and shear failure of the cement at the casing-cement interface as the pressure and temperature conditions of the formation and borehole vary during production. The numerical model which includes the formation pressure, unlike others proposed, was designed by stages under finite element discretization and validated by analytical models. Results show that increasing the formation temperature increases the probability of tensile and shear failure in the cement, while increasing the wellbore temperature decreases these probabilities. On the other hand, the decrease in the well pressure reduces the probability of shear failure and increases the tensile failure. In the case of formation pressure, the opposite occurs.

Abstract Activity cliffs are defined as compounds with high structure similarity but large potency difference. Identification of activity cliffs have a significant impact in lead optimization in medicinal chemistry, and computational applications such as the development of predictive models and the selection of queries for similarity searching. Therefore, the identification of compounds highly associated with activity cliffs in a given data set i.e., ‘activity cliff generators’, is of major relevance. Herein, we report the identification of activity cliffs and structure-activity relationships of a set of 289 synthetic compounds tested in a G protein-coupled receptor kinase, GRK. To account for information of multiple structure representations we used mean Structure-Activity Landscape Index (SALI). Structural fragments responsible for the activity are discussed.

Resumen Los acantilados de actividad se definen como compuestos con alta similitud estructural, pero también con alta diferencia en potencia. Estos compuestos tienen un impacto significativo en la optimización de líderes en química medicinal y en aplicaciones computacionales, como el desarrollo de modelos predictivos y en la selección de moléculas de referencia en búsquedas basadas en similitud molecular. Por lo tanto, es de gran relevancia la identificación de compuestos altamente asociados con los acantilados como por ejemplo los “generadores de acantilados de actividad”. En este trabajo se reportan la identificación de acantilados de actividad y las relaciones estructura-actividad de un grupo de 289 compuestos obtenidos por síntesis química que han sido evaluados a través de una proteína quinasa reguladora de receptores acoplados a proteínas-G. Para considerar la información de múltiples representaciones estructurales, se empleó el promedio del índice SALI (Structure-Activity Landscape Index) y se discuten también fragmentos estructurales responsables de la actividad biológica.

Abstract. UNIIQUIM database contains molecules from Mexican plants, one of the richest sources of bioactive molecules in the world. Here, we describe the chemical and toxicological profile of molecules with analgesic activity from UNIIQUIM. Most of the compounds are likely to interact with opioid receptors. The predicted acute toxicity is low and none is predicted mutagenic. Given the structural diversity, and biological and toxicity profiles, these molecules represent a new avenue in the search of molecules with antinociceptive activity.

Resumen. La base de datos UNIIQUIM contiene moléculas de plantas mexicanas, una de las fuentes más ricas de moléculas bioactivas en el mundo. Aquí se describe la química y el perfil toxicológico de moléculas con actividad analgésica obtenidas de UNIIQUIM. La mayoría de los compuestos son propensos a interactuar con los receptores opioides. La toxicidad aguda predicha es baja y ningún compuesto se predice mutagénico. Dada su diversidad estructural y su perfil biológico y toxicológico, son atractivas moléculas líderes con actividad antinociceptiva.

INTRODUCTION: Mesoamerican nephropathy, also known as chronic kidney disease of unknown etiology, is widespread in Pacific coastal Central America. The cause of the epidemic is unknown, but the disease may be linked to multiple factors, including diet as well as environmental and occupational exposures. As many as 50% of men in some communities have Mesoamerican nephropathy. OBJECTIVE: Describe prevalence of reduced glomerular filtration rate in a region of Nicaragua suspected to harbor high rates of Mesoamerican nephropathy; and investigate potential risk factors for such reduction associated with agricultural work (such as pesticide exposure and specific agricultural tasks associated with increased heat stress); sugar consumption; and traditional factors such as age, sex, diabetes, hypertension and nephrotoxic medication use. METHODS: This study uses a cross-sectional design with nested case-control analysis. Cases were individuals with estimated glomerular filtration rates of <60mL/min/1.73m² and controls were individuals with those >90mL/min/1.73m², estimated using serum creatinine. Data on nutrition, past medical history, medication and substance use, and agricultural behaviors and exposures were collected using medical questionnaires from June through August, 2012. Venous blood and urine samples were collected to assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and blood pressure measurements were made using standard techniques. Analyses were conducted using chi square, and univariate and multiple logistic regression. RESULTS: Of 424 individuals in the study, 151 had an occupational history in agriculture. Prevalence of glomerular filtration rate <60mL/min/1.73m² was 9.8% among women and 41.9% among men (male to female ratio = 4.3, p<0.0001). Proteinuria ≥300 mg/dL was observed in <10% of participants with decreased glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated with decreased glomerular filtration rate. Although systolic and diastolic blood pressure was higher among participants with decreased glomerular filtration rate (p <0.001), hypertension was uncommon. Significant agricultural risk factors for reduced glomerular filtration rate included increased lifetime days cutting sugarcane during the dry season (OR 5.86, 95% CI 2.45 - 14.01), nondeliberate pesticide inhalation (OR 3.31, 95% CI 1.32 - 8.31), and sugarcane chewing (OR 3.24, 95% CI 1.39 - 7.58). CONCLUSIONS: Our findings demonstrate a high prevalence of chronic kidney disease not linked to traditional risk factors, and suggest it may be associated instead with occupational exposure to heat stress in conjunction with pesticide inhalation, sugarcane chewing and sugar intake during the workday.