Urolithiasis develops endothelial dysfunction as a clinical feature

An increased risk of cardiovascular morbidity has been reported in lithiasic patients. In this context, endothelial dysfunction (ED), an earlier status of atherogenesis, has been identified in hyperoxaluria rat models of urolithiasis. Objective: The purpose of this study was to determine the endothelial vascular function in patients with urolithiasis in relation to systemic inflammatory, oxidative stress, and vascular function serum markers. Methods: A cross-sectional study was performed between 27 urolithiasic patients, matched for age and sex, with 27 healthy patients. Endothelial function was assessed by measuring flow-mediated dilation (Celermajer method). Fasting blood was collected to determine metabolic parameters (glucose and lipid profile), along with serum CRP, IL-6, MDA, ADMA, and VCAM-1. Results: Both the control and urolithiasis groups were homogenous in anthropometric, exploration, and general laboratory measures. Flow-mediated dilation (%FMD) was 11.85% (SE: 2.78) lower in the lithiasis group (p < 0.001). No significant differences were achieved between groups when CRP, IL-6, MDA, ADMA, and VCAM-1 were compared, although slightly higher values of CRP, ADMA, and VCAM-1 were detected in the lithiasic group. A correlation was not reached in any of the serum markers when they were related to flow-mediated values, although a slight negative correlation trend was observed in MDA, VCAM-1, and IL-6 values. Conclusions: Endothelial dysfunction constitutes an important disorder related to urolithiasis patients. It must be considered as an early feature responsible for future cardiovascular events. Our study did not find a significant association between inflammatory, oxidative stress, endothelial serum markers, and flow-mediated dilation.Puerta de Hierro-Segovia de Arana Research Institut

Modelo estratégico integral para la implementación del Sistema de Gestión de la Seguridad y Salud en el trabajo (SG-SST) en la empresa Postobon S.A.

Con la realización de este proyecto identificamos mediante la aplicación de la matriz de estándares mínimos en qué estado o fase de implementación del sistema de Gestión de Salud y Seguridad en el trabajo se encuentra la empresa Postobon SA. En línea con lo establecido por el Ministerio del trabajo en el decreto 052 del 12 de enero del 2017 con el objetivo de asegurar el cumplimiento de la normatividad vigente y hacer de Postobón el mejor lugar para trabajar con políticas claras y aplicables en cuanto a Salud y seguridad en el trabajo, con una planificación y seguimiento a los programas de gestión del riesgo ocupacional que a la fecha están pendientes, ejecutando de manera ordenada y con cronograma de ejecución las acciones planeadas y evaluando sus impactos bajo el seguimiento y auditoría permanente para sobre la marcha ir haciendo ajustes y promoviendo acciones de mejora.With the realization of this project, we identified the company Postobon SA through the application of the matrix of the deadlines in the status of the application of the Occupational Health and Safety Management system. In line with the provisions of the Ministry of Labor in decree 052 of January 12, 2017 with the aim of ensuring compliance with current regulations and make Postobón the best place to work with clear policies and the corresponding in the form health and safety at work, with planning and monitoring of occupational activity management programs that are pending date, executing in an orderly manner and with execution schedule the planned actions and evaluating their effects under monitoring and audit permanent for on Going to the adjustments and promoting improvement actions

Acute and Reproductive Effects of Align®, an Insecticide Containing Azadirachtin, on the Grape Berry Moth, Lobesia botrana

Azadirachtin, derived from the neem tree, Azadirachta indica A. Juss (Sapindales: Meliaceae), seems promising for use in integrated pest management programs to control a variety of pest species. A commercial formulation of azadirachtin, Align®, has been evaluated against different developmental stages of the European grape berry moth, Lobesia botrana Denis and Schiffermüller (Lepidoptera: Tortricidae). When administered orally, Align reduced the fecundity and fertility of adults treated with 1, 5, and 10 mg litre-1. At the highest doses, fecundity and fertility were zero, but longevity was not affected. An LC50 of 231.5 mg litre-1 was obtained when Align was sprayed on eggs less than 1 day old. Hatching of all egg classes was significantly reduced, and this reduction was more pronounced for eggs less than 24 h old. LC50 values of 2.1 mg litre-1 for first instars and 18.7 mg litre-1 for third instars were obtained when Align was present in the diet. Larvae reared on a diet containing different concentrations of Align did not molt into adults at the highest concentrations (0.3, 0.6, 1.2), and 50% molted at the lowest concentration (0.15). Phenotypic effects included inability to molt properly and deformities. The combination of acute toxicity and low, effective concentrations of Align observed in this study could lead to the inclusion of insecticides containing azadirachtin in integrated management programs against this pest

Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity

Background and Purpose Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK. Experimental Approach Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting. Key Results Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice. Conclusion and Implications These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series

[Background]: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular.[Results]: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80.[Conclusions]: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.M.M was supported by two research grants from Ministry of Economy and Competitiveness ISCIII-FIS grants (PI 12/02684): “Predictores genómicos de respuesta a la quimioterapia neoadyuvante con docetaxel-carboplatino en pacientes con cáncer de mama triple negativo”/“Genomic predictors of response to neoadjuvant chemotherapy with docetaxel-carboplatin in patients with triple negative breast cancer”; and (PI 15/00117): “Cáncer de mama triple negative: Predicción de respuesta a docetaxel-carboplatino neoadyuvante mediante caracterización de TILs y firmas inmunes basadas en secuenciación masiva de RNA”/” Triple negative breast cancer: Prediction of response to neoadjuvant docetaxel-carboplatin by characterization of TILs and immune signatures based on massive RNA sequencing”. C.M.P was supported by funds from the NCI Breast SPORE program (P50-CA58223).Peer reviewe

Differential contribution of renal cytochrome P450 enzymes to kidney endothelial dysfunction and vascular oxidative stress in obesity

Arachidonic acid (AA)-derived cytochrome P450 (CYP) derivatives, epoxyeicosatrienoic acids (EETs) and 20-hidroxyeicosatetranoic acid (20-HETE), play a key role in kidney tubular and vascular functions and blood pressure. Altered metabolism of CYP epoxygenases and CYP hydroxylases has differentially been involved in the pathogenesis of metabolic disease-associated vascular complications, although the mechanisms responsible for the vascular injury are unclear. The present study aimed to assess whether obesity-induced changes in CYP enzymes may contribute to oxidative stress and endothelial dysfunction in kidney preglomerular arteries. Endothelial function and reactive oxygen species (ROS) production were assessed in interlobar arteries of obese Zucker rats (OZR) and their lean counterparts lean Zucker rats (LZR) and the effects of CYP2C and CYP4A inhibitors sulfaphenazole and HET0016, respectively, were examined on the endothelium-dependent relaxations and O2 − and H2O2 levels of preglomerular arteries. Non-nitric oxide (NO) non-prostanoid endothelium-derived hyperpolarization (EDH)-type responses were preserved but resistant to the CYP epoxygenase blocker sulfaphenazole in OZR in contrast to those in LZR. Sulfaphenazole did not further inhibit reduced arterial H2O2 levels, and CYP2C11/CYP2C23 enzymes were downregulated in intrarenal arteries from OZR. Renal EDH-mediated relaxations were preserved in obese rats by the enhanced activity and expression of endothelial calcium-activated potassium channels (KCa). CYP4A blockade restored impaired NO-mediated dilatation and inhibited augmented O2 − production in kidney arteries from OZR. The current data demonstrate that both decreased endothelial CYP2C11/ CYP2C23-derived vasodilator H2O2 and augmented CYP4A-derived 20-HETE contribute to endothelial dysfunction and vascular oxidative stress in obesity. CYP4A inhibitors ameliorate arterial oxidative stress and restore endothelial function which suggests its therapeutic potential for the vascular complications of obesity-associated kidney injury

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Orientaciones específicas para la incorporación de tecnología en procesos de formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas en contextos de diversidad para el diseño de secuencias de enseñanza aprendizaje

Las Tecnologías de la Información y de la Comunicación (TIC) se han transformado en un elemento de innovación dentro del conocimiento humano. Aplicadas directamente a la disciplina académica, las TIC se han ganado un espacio debido al creciente interés de este tipo de herramientas por parte de los docentes. No obstante, al día de hoy, en Latinoamérica el uso de TIC no es masivo. Su implementación aún está en una etapa inicial, y esto es debido a diversos factores. Algunos tienen que ver con el poco seguimiento que se realiza al implementar este tipo de tecnologías en las instituciones educativas; la limitada formación es una debilidad. En una escuela, el profesor que no ha sido preparado adecuadamente en el uso de TIC difícilmente logrará utilizarlas adecuadamente, y sus metodologías de aula serán, probablemente, idénticas a las que existían previas a su implementación. Existe una gran diferencia entre conocer una herramienta y dominarla; el dominio se logra, por ejemplo, al conocer las ventajas y desventajas que posee una herramienta determinada en conexión directa con los contenidos y las necesidades de los estudiantes. El dominio de las TIC otorga al docente de aula la posibilidad de tomar decisiones que tiendan a la efectividad del proceso educativo, puesto que las TIC no son solo un conjunto de herramientas, sino que, además, son orientables hacia un área u otra dependiendo de factores variables propios del proceso. Teniendo en cuenta el contexto anterior, este documento contiene algunas orientaciones para el uso del material desarrollado en el área de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas del Proyecto ALTER-NATIVA, el cual va dirigido a la formación de profesores que atienden poblaciones en contexto de diversidad con incorporación de las TIC. Es importante anotar que las actividades que se proponen son una posibilidad distinta de asumir la enseñanza de las ciencias naturales, lo cual a su vez implica reflexión y evaluación constante de la práctica de los docentes de esta área; que los compromete también con los desarrollos tecnológicos actuales, lo cual conlleva analizar y canalizar sus esfuerzos para diseñar y gestionar mecanismos que permitan la incorporación de las TIC en sus prácticas, pues se considera que estas posibilitan colaborar en la construcción de mundos posibles cercanos a los ideales de participación, igualdad y equidad (Alter -nativa , 2012). Estas orientaciones específicas tienen un doble propósito: primero, cobijan algunas recomendaciones, las cuales son una propuesta de uso para aprovechar al máximo el material que se propone en el estudio de las Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas, para las poblaciones objeto de estudio. Para el desarrollo de las actividades planteadas es necesario que los estudiantes para profesor y profesores de escuelas, colegios y universidades de las áreas de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas, como posibles usuarios de este material, las perciban como un recurso que tiene un potencial y que, para su desarrollo, se hace necesario tener presente el diseño y estructura didáctica, los objetivos temáticos, la infraestructura, los recursos tecnológicos, las necesidades y características de las poblaciones con quien se vaya a utilizar, entre otros aspectos. Y segundo, estas orientaciones tienen como propósito ofrecer elementos para la formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas en su acción pedagógica y didáctica; se involucran las prácticas profesionales de diseño y elaboración de objetos didácticos y de los objetos virtuales de aprendizaje (OVA) como casos específicos de estos. Tomando como referencia lo anterior, se plantea como objetivos central de este texto el presentar algunas orientaciones que es necesario tener en cuenta a la hora incorporar TIC en la formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas. De igual forma, unos objetivos específicos serían los siguientes: a) Establecer unas orientaciones que sean consideradas a la hora de usar los recursos virtuales como los Objetos Virtuales de aprendizaje (OVA) que fueron diseñados como parte del proyecto ALTER-NATIVA en el área de ciencias naturales, lenguaje y matemáticas. b) Favorecer el aprendizaje de las ciencias naturales, lenguaje y matemáticas en las poblaciones objeto de estudio a través del uso de las TIC. c) Resaltar la importancia que tiene el uso de las TIC para concebir el aprendizaje como un sistema de interacción y no como transmisión de información solamente. d) Aportar a la reflexión y formación de docentes con una cultura tecnológica que les permita afrontar su labor pedagógica y didáctica en ámbitos de diversidad. e) Proporcionar unos elementos teóricos y de uso de las TIC que les admita la planeación, el diseño, desarrollo, uso y evaluación de objetos virtuales u OVA dentro de un ambiente virtual de aprendizaje

Casar - Casetas Alimentarias Rodantes - Proyecto de Emprendimiento Social

El PNDU estableció en 2015, un pacto para que todas las personas en el mundo entero tengan las mismas oportunidades. Para ello estableció los ODS, y es en uno de ellos y en el que específicamente se refiere al principio de Hambre Cero, que se establece el deseo de atender la necesidad manifiesta en problemáticas de alimentación como propuesta de proyecto social. Este proyecto, diseña esa alternativa, en la que se busca ofrecer un servicio alimentario, completo y con buenos niveles nutricionales, en una población identificada de la ciudad de Bogotá D.C., con un elemento innovador y pionero, al brindar una alternancia de movilidad para llevar esos alimentos, y complementado con un servicio de acompañamiento profesional para orientar de la mejor manera las inquietudes y necesidades de la población favorecida con esta propuesta. El diseño de la propuesta, presenta toda una estructura dinámica que va desde la esencia misma y razón de ser, hasta su componente operativo y financiero, presentando con todo ello, una alternativa para querer responder al problema identificado.The UNDP established in 2015, a pact so that all people throughout the world have the same opportunities. For this, it established the SDGs, and it is in one of them and in which it specifically refers to the Zero Hunger principle, that the desire to address the manifest need in food problems is established as a social project proposal. This project designs that alternative, which seeks to offer a complete food service with good nutritional levels, in an identified population of the city of Bogotá D.C., with an innovative and pioneering element, by providing an alternation of mobility to carry those foods, and complemented with a professional accompaniment service to better guide the concerns and needs of the population favored with this proposal. The design of the proposal presents an entire dynamic structure that goes from the very essence and reason for being, to its operational and financial component, presenting with all this, an alternative to want to respond to the identified problem