Kinetic studies of the release profiles of antiepileptic drug released from a nanostructured TiO2 matrix.

In this paper is reported the “in vitro†release kinetic studies of antiepileptic drugs released from an inorganic, titanium oxide (TiO2) porous matrix. In order to determine the drug release mechanism, the experimental values were fitted to different mathematical models: zero-order, firs-order, Higuchi, Hixson-Crowel and Peppas. TiO2 was prepared by the sol-gel method adding valproic acid (VPA) or phenytoine (DHP) during the titanium n-butoxide hydrolysis step. The drug-TiO2 systems were observed by scanning electron microscopy. The “in vitro†release experiments were performed at laboratory scale following the United States Pharmacopeia (USP) standards. The obtained materials have a morphology of nanoparticle agglomerates. The particles have different sizes with some roughness and spherical shape. Peppas model suggests for both systems, that the release mechanism is controlled by two parallel processes. The first one is by diffusion of the drug through the matrix and the second is related to a gradient of constant diffusion by ingress of the solvent in the matrix

Effects of Gamma Irradiation on Curcumin

In this study, remnants concentrations of curcumin in Curcuma longa (organic turmeric powder) were determined after it was exposed to irradiation doses of 1, 2 and 3 kGy. Curcumin analysis was performed using the analyte-sensitive impulse differential polarography technique (LOD: 0.621 ppm and LOQ: 2.130 ppm). The results obtained showed a decreasing concentration of curcumin as a function of the irradiation dose. This reduction is low in terms of affecting the product’s quality with respect to its concentration

El precio del durazno para la toma de decisiones de los productores mexicanos

Peach producers in Mexico form their production expectations based on the future price; they wait for the price to increase in order to continue with the agricultural activity, reason why they do not make the decision of seeking other uses and markets for the fruit, different from the fresh market. The objective of this study was to analyze the dynamics of the formation of the market price of peach in Mexico, its trend and volatility, in order to predict its trajectory through time. The hypothesis was that peach prices present high volatility and a negative trend that converges in a price with a constant. With the methodology of a dynamic model under a simple market, a differential second degree equation and a Brownian equation, it was found that the real price of peach presented severe fluctuation with negative trend; that the trajectory in time led the price of the fruit towards a constant equilibrium price, although it was low compared to the levels in previous periods. Thus, it was confirmed that the future price will not increase in the next 15 years and, as consequence, facing this scenario of uncertainty, the producers of this fruit could cease to continue investing in the activity.Los productores de durazno en México forman sus expectativas de producción basadas en el precio futuro; estos esperan que el precio aumente para seguir con la actividad agrícola, razón por la cual no toman la decisión de buscar otros usos y mercados para la fruta, diferentes al mercado en fresco. El objetivo fue analizar la dinámica de la formación del precio de mercado del durazno en México, su tendencia y volatilidad a fin de pronosticar la trayectoria de este en el tiempo. La hipótesis fue que los precios del durazno presentan alta volatilidad y tendencia negativa que convergen a un precio con constante. Con la metodología de un modelo dinámico bajo un mercado simple, una ecuación diferencial de segundo grado y una ecuación browniana se obtuvo que el precio real del durazno presentó severas oscilaciones con tendencia negativa; que la trayectoria del tiempo condujo al precio de la fruta hacia un precio constante de equilibrio, pero que este fue bajo con respecto a los niveles de los periodos anteriores, por lo que se comprobó que el precio del fruto no aumentará en los próximos 15 años y en consecuencia, ante este escenario de incertidumbre, los productores de dicho fruto podrían dejar de seguir invirtiendo en la actividad

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe