Mathematical Modeling for the Assessment of Public Policies in the Cancer Health-Care System Implemented for the Colombian Case.

The incidence of cancer has been constantly growing worldwide, placing pressure on health systems and increasing the costs associated with the treatment of cancer. In particular, low- and middle-income countries are expected to face serious challenges related to caring for the majority of the world's new cancer cases in the next 10 years. In this study, we propose a mathematical model that allows for the simulation of different strategies focused on public policies by combining spending and epidemiological indicators. In this way, strategies aimed at efficient spending management with better epidemiological indicators can be determined. For validation and calibration of the model, we use data from Colombia-which, according to the World Bank, is an upper-middle-income country. The results of the simulations using the proposed model, calibrated and validated for Colombia, indicate that the most effective strategy for reducing mortality and financial burden consists of a combination of early detection and greater efficiency of treatment in the early stages of cancer. This approach is found to present a 38% reduction in mortality rate and a 20% reduction in costs (% GDP) when compared to the baseline scenario. Hence, Colombia should prioritize comprehensive care models that focus on patient-centered care, prevention, and early detection.

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. APPROACH AND RESULTS: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. CONCLUSIONS: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.

Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.

Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation. The CO consumption led to the lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-cholesterol concentration and the lowest respiratory capacity and fatty acid oxidation in the mitochondria. The absence of PPARα decreased alpha diversity and increased LPS concentration particularly in the CO group, and increased insulin sensitivity in the groups fed SO or OO. These results indicate that consuming mono or polyunsaturated fatty acids produced health benefits at the recommended intake but a high concentration of oils (three times the recommended oil intake in rodents) significantly decreased the microbial alpha-diversity independent of the type of oil.

Importancia de la farmacovigilancia en medicina herbaria / Importance of pharmacovigilance in herbal medicine

Introducción: el uso de hierbas medicinales para la prevención y el tratamiento de diversas enfermedades es una práctica ancestral. A pesar del papel beneficioso y tradicional de las mismas en diferentes comunidades, hay que considerar que también pueden provocar reacciones adversas y toxicidad. Objetivo: analizar las notificaciones sobre reacciones adversas de productos medicinales a base de hierbas durante el período 2010-2016 en la provincia del Chaco, Argentina. Métodos: estudio retrospectivo, transversal y descriptivo. Se evaluaron las notificaciones de reacciones adversas a partir de los datos obtenidos de la ficha de Comunicación de Eventos Adversos por uso de Medicamentos Fitoterápicos, Productos Vegetales y/o Preparados de Drogas Vegetales, recibidas de farmacias y centros de salud de la provincia del Chaco, Argentina, como efectores periféricos del Sistema Nacional de Farmacovigilancia de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT). Resultados: se recibieron un total de 129 notificaciones, se observó un predominio de reacciones adversas por el uso de productos medicinales a base de hierbas en el sexo femenino y un considerable porcentaje de las mismas que incluyó a lactantes y niños, siendo el paico ( Chenopodium ambrosioides L.) el más reportado en este grupo etario y sen (Cassia angustifolia Vahl.) en adultos. La mayoría de las reacciones adversas notificadas correspondieron a trastornos del sistema gastrointestinal. En cuanto a la intensidad e imputabilidad predominaron las leves y probables respectivamente. Conclusiones: es primordial la vigilancia continua de las medicinas a base de hierbas para promover su uso seguro sobre todo en poblaciones vulnerable(AU)

Introduction: Ever since ancient times medicinal herbs have been used to prevent and treat a variety of diseases. Despite the beneficial traditional role of medicinal herbs in various communities, their potential for causing adverse reactions and toxicity should also be borne in mind. Objective: Analyze the reports of adverse reactions by herbal medicinal products issued from 2010 to 2016 in the province of Chaco, Argentina. Methods: A descriptive cross-sectional retrospective study was conducted to evaluate the reports of adverse reactions received from pharmacies and healthcare institutions from the province of Chaco, Argentina, at the National System of Pharmacovigilance of the National Drug, Food and Medical Technology Administration (ANMAT). The study was based on official forms for the report adverse events caused by the use of phytotherapeutic drugs, plant products and/or plant drug preparations. Results: A total 129 reports were received. Adverse reactions caused by the use of herbal medicinal products prevailed in the female gender, whereas a large percentage affected infants and children. Paico (Chenopodium ambrosioides L.) was the species most commonly reported in this age group and sen (Cassia angustifolia Vahl.) among adults. Most of the adverse reactions reported were gastrointestinal disorders. As to intensity and imputability, there was a predominance of mild and probable reactions, respectively. Conclusions: Permanent vigilance of herbal medicines is crucial to promote their safe use, particularly in vulnerable populations(AU)

Importancia de la farmacovigilancia en medicina herbaria / Importance of pharmacovigilance in herbal medicine

Introducción: el uso de hierbas medicinales para la prevención y el tratamiento de diversas enfermedades es una práctica ancestral. A pesar del papel beneficioso y tradicional de las mismas en diferentes comunidades, hay que considerar que también pueden provocar reacciones adversas y toxicidad. Objetivo: analizar las notificaciones sobre reacciones adversas de productos medicinales a base de hierbas durante el período 2010-2016 en la provincia del Chaco, Argentina. Métodos: estudio retrospectivo, transversal y descriptivo. Se evaluaron las notificaciones de reacciones adversas a partir de los datos obtenidos de la ficha de Comunicación de Eventos Adversos por uso de Medicamentos Fitoterápicos, Productos Vegetales y/o Preparados de Drogas Vegetales, recibidas de farmacias y centros de salud de la provincia del Chaco, Argentina, como efectores periféricos del Sistema Nacional de Farmacovigilancia de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT). Resultados: se recibieron un total de 129 notificaciones, se observó un predominio de reacciones adversas por el uso de productos medicinales a base de hierbas en el sexo femenino y un considerable porcentaje de las mismas que incluyó a lactantes y niños, siendo el paico ( Chenopodium ambrosioides L.) el más reportado en este grupo etario y sen (Cassia angustifolia Vahl.) en adultos. La mayoría de las reacciones adversas notificadas correspondieron a trastornos del sistema gastrointestinal. En cuanto a la intensidad e imputabilidad predominaron las leves y probables respectivamente. Conclusiones: es primordial la vigilancia continua de las medicinas a base de hierbas para promover su uso seguro sobre todo en poblaciones vulnerable(AU)

Introduction: Ever since ancient times medicinal herbs have been used to prevent and treat a variety of diseases. Despite the beneficial traditional role of medicinal herbs in various communities, their potential for causing adverse reactions and toxicity should also be borne in mind. Objective: Analyze the reports of adverse reactions by herbal medicinal products issued from 2010 to 2016 in the province of Chaco, Argentina. Methods: A descriptive cross-sectional retrospective study was conducted to evaluate the reports of adverse reactions received from pharmacies and healthcare institutions from the province of Chaco, Argentina, at the National System of Pharmacovigilance of the National Drug, Food and Medical Technology Administration (ANMAT). The study was based on official forms for the report adverse events caused by the use of phytotherapeutic drugs, plant products and/or plant drug preparations. Results: A total 129 reports were received. Adverse reactions caused by the use of herbal medicinal products prevailed in the female gender, whereas a large percentage affected infants and children. Paico (Chenopodium ambrosioides L.) was the species most commonly reported in this age group and sen (Cassia angustifolia Vahl.) among adults. Most of the adverse reactions reported were gastrointestinal disorders. As to intensity and imputability, there was a predominance of mild and probable reactions, respectively. Conclusions: Permanent vigilance of herbal medicines is crucial to promote their safe use, particularly in vulnerable populations(AU)

Substrate and Lewis Acid Coordination Promote O-O Bond Cleavage of an Unreactive L2CuII2(O22-) Species to Form L2CuIII2(O)2 Cores with Enhanced Oxidative Reactivity.

Copper-dependent metalloenzymes are widespread throughout metabolic pathways, coupling the reduction of O2 with the oxidation of organic substrates. Small-molecule synthetic analogs are useful platforms to generate L/Cu/O2 species that reproduce the structural, spectroscopic, and reactive properties of some copper-/O2-dependent enzymes. Landmark studies have shown that the conversion between dicopper(II)-peroxo species (L2CuII2(O22-) either side-on peroxo, SP, or end-on trans-peroxo, TP) and dicopper(III)-bis(µ-oxo) (L2CuIII2(O2-)2: O) can be controlled through ligand design, reaction conditions (temperature, solvent, and counteranion), or substrate coordination. We recently published ( J. Am. Chem. Soc. 2012 , 134 , 8513 , DOI: 10.1021/ja300674m ) the crystal structure of an unusual SP species [(MeAN)2CuII2(O22-)]2+ (SPMeAN, MeAN: N-methyl-N,N-bis[3-(dimethylamino)propyl]amine) that featured an elongated O-O bond but did not lead to O-O cleavage or reactivity toward external substrates. Herein, we report that SPMeAN can be activated to generate OMeAN and perform the oxidation of external substrates by two complementary strategies: (i) coordination of substituted sodium phenolates to form the substrate-bound OMeAN-RPhO- species that leads to ortho-hydroxylation in a tyrosinase-like fashion and (ii) addition of stoichiometric amounts (1 or 2 equiv) of Lewis acids (LA's) to form an unprecedented series of O-type species (OMeAN-LA) able to oxidize C-H and O-H bonds. Spectroscopic, computational, and mechanistic studies emphasize the unique plasticity of the SPMeAN core, which combines the assembly of exogenous reagents in the primary (phenolates) and secondary (Lewis acids association to the MeAN ligand) coordination spheres with O-O cleavage. These findings are reminiscent of the strategy followed by several metalloproteins and highlight the possible implication of O-type species in copper-/dioxygen-dependent enzymes such as tyrosinase (Ty) and particulate methane monooxygenase (pMMO).

Transient neonatal zinc deficiency due to a new autosomal dominant mutation in gene SLC30A2 (ZnT-2).

Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to that of acrodermatitis enteropathica but is caused by a low zinc concentration in maternal breast milk. TNZD becomes clinically evident during breastfeeding and is resolved by weaning and the introduction of complementary nutrition. We present a 4-month-old girl with TNZD due to a new autosomal dominant mutation (663delC) in the maternal SLC30A2 gene not previously described in the literature.