Intravitreal methotrexate in type B lymphoblastic leukemia—Case Report

Leukemia is a common neoplasia that, in its progress, can have ocular involvement due to direct infiltration or secondary to hematological alterations typical of the disease. These findings are consistent with an involvement of the central nervous system and are thus related to the prognosis. Despite the existing systemic therapies, there needs to be more literature that shows the treatment in the ocular involvement of this disease. A case report of a child with ocular involvement due to treatment-refractory acute lymphoblastic leukemia, successfully managed with intravitreal methotrexate, is presented

Second GHEP-ISFG exercise for DVI: “DNA-led” victims’ identification in a simulated air crash

The Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) has organized a second collaborative exercise on a simulated case of Disaster Victim Identification (DVI), with the participation of eighteen laboratories. The exercise focused on the analysis of a simulated plane crash case of medium-size resulting in 66 victims with varying degrees of fragmentation of the bodies (with commingled remains). As an additional difficulty, this second exercise included 21 related victims belonging to 6 families among the 66 missings to be identified. A total number of 228 post-mortem samples were represented with aSTR and mtDNA profiles, with a proportion of partial aSTR profiles simulating charred remains. To perform the exercise, participants were provided with aSTR and mtDNA data of 51 reference pedigrees —some of which deficient—including 128 donors for identification purposes. The exercise consisted firstly in the comparison of the post-mortem genetic profiles in order to re-associate fragmented remains to the same individual and secondly in the identification of the re-associated remains by comparing aSTR and mtDNA profiles with reference pedigrees using pre-established thresholds to report a positive identification. Regarding the results of the post-mortem samples re-associations, only a small number of discrepancies among participants were detected, all of which were from just a few labs. However, in the identification process by kinship analysis with family references, there were more discrepancies in comparison to the correct results. The identification results of single victims yielded fewer problems than the identification of multiple related victims within the same family groups. Several reasons for the discrepant results were detected: a) the identity/non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, b) some laboratories failed to use all family references to report the DNA match, c) In families with several related victims, some laboratories firstly identified some victims and then unnecessarily used their genetic information to identify the remaining victims within the family, d) some laboratories did not correctly use “prior odds” values for the Bayesian treatment of the episode for both post-mortem/post-mortem re-associations as well as the ante-mortem/post-mortem comparisons to evaluate the probability of identity. For some of the above reasons, certain laboratories failed to identify some victims. This simulated “DNA-led” identification exercise may help forensic genetic laboratories to gain experience and expertize for DVI or MPI in using genetic data and comparing their own results with the ones in this collaborative exercise.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewe

Manejo Multidisciplinario del Adenocarcinoma de Páncreas: Guía de Práctica Clínica AUNA

Introduction: This article provides recommendations for the Multidisciplinary Management of Pancreatic Adenocarcinoma in the RED AUNA. Methods: A systematic search of clinical practice guidelines (CPG) similar to topics of interest was developed, it was assessed with the AGREE II instrument, a list of questions was elaborated under the PICO structure, a de novo search was carried out prioritizing reviews systematic with or without meta-analysis, followed by primary studies, the elaboration of the evidence tables and the evaluation of the global quality for the outcomes of the clinical questions was carried out following the GRADE methodology. Results: 5 PICO questions corresponding to initial management and systemic management were formulated with 18 recommendations regarding the most effective method for pathological diagnosis, biliary drainage and the most effective and safe systemic treatment in the neoadjuvant, adjuvant and metastatic setting. Conclusions: This article summarizes the methodology and evidence-based recommendations of the CPG for the multidisciplinary management of pancreatic adenocarcinoma of the AUNA Clinic Network.Introducción: Este artículo brinda recomendaciones para el Manejo Multidisciplinario del Adenocarcinoma de Páncreas en la RED AUNA. Métodos: Se desarrolló una búsqueda sistemática de guías de práctica clínica (GPC) similares al tópico de interés, se valoró con el instrumento AGREE II, se elaboró un listado de preguntas bajo la estructura PICO, se realizó una búsqueda de novo priorizando revisiones sistemáticas con o sin meta-análisis, seguida de estudios primarios, la elaboración de las tablas de evidencia y la evaluación de la calidad global para los desenlaces de las preguntas clínicas se realizó siguiendo la metodología GRADE. Resultados: Se formularon 5 preguntas PICO correspondientes al manejo inicial y manejo sistémico con 18 recomendaciones respecto al método más efectivo para el diagnóstico patológico, el drenaje biliar y el tratamiento sistémico más efectivo y seguro en el escenario neoadyuvante, adyuvante y metastásico. Conclusiones: El presente artículo resume la metodología y las recomendaciones basadas en evidencia de la GPC para el manejo multidisciplinario del Adenocarcinoma de páncreas de la Red de Clínicas AUNA

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Adsorción de un compuesto activo farmacéutico (PhACs) utilizando biocarbón activado elaborado con Eichhornia crassipes

Los compuestos activos farmacéuticos (PhACs) se utilizan ampliamente por los seres humanos, entre uso personal o veterinario y como consecuencia, en los últimos años, se ha presentado un aumento en las concentraciones de estos catalogándolos como contaminantes emergentes (CE), generándose una situación alarmante por la limitada información de los impactos generados por estos PhACs y la baja eficiencia en su remoción en los sistemas de tratamientos de aguas. Con base en esta situación se evalúa el desarrollo de un biocarbón activado aprovechando las propiedades del jacinto de agua (WJ) como adsorbente natural, con la expectativa de obtener una remoción de los PhACs, en este caso acetaminofén, de los recursos hídricos y determinar la capacidad de adsorción del biocarbón. Se desarrolló el biocarbón implementando el método de activación químico-físico, realizando una impregnación de H_3 PO_4 al 30% con una proporción de 1:4 (p/p) durante 24 horas y sometiendo el material a temperaturas superiores a 110°C en distintos intervalos de tiempo. La adsorción fue llevada a cabo utilizando una solución problema de 1200 ml de agua y 964.8 mg de acetaminofén dividida en 6 partes de 200 ml a las cuales se les adicionaron 10 g de biocarbón con tiempos de contacto de 20, 40, 60, 80, 90 y 100 minutos. Todos los experimentos se realizaron por duplicado. Al final de la experiencia se analizó por HPLC la capacidad de remoción del adsorbente, obteniendo porcentajes de adsorción de acetaminofén del 12.6196% en promedio, también se realiza la medición del pH observando cambios inferiores a 0.09 con respecto al pH inicial en las muestras, equivalentes a 6.11 y 6.09. Los resultados obtenidos comprueban la capacidad adsortiva del biocarbón desarrollado a partir de jacinto de agua, además, se analiza que el pH y el tiempo de contacto no influyen significativamente en el proceso de adsorción

Tipificación del consumo de la generación "Millennial" en Medellín en los estratos 4, 5 y 6

207 páginasSatisfacer las necesidades de los “millennials” se ha convertido en un gran reto para las empresas que cada día se encuentran con consumidores más exigentes, y por lo tanto, para las marcas es más difícil establecer fidelidad. Por lo anterior, se decidió para la investigación plantear la siguiente pregunta ¿Cuáles oportunidades estratégicas ayuden a las compañías a llegarle de una manera eficiente a dichos consumidores en la ciudad de Medellín en los estratos cuatro, cinco y seis?. Con el propósito de responder a la pregunta de investigación, se investigó los patrones de consumo de los “millennials” de estratos cuatro, cinco y seis en la ciudad de Medellín, cuáles eran los verdaderos motivos que lo impulsan a la compra y que atributos específicos buscan en los productos o servicios que adquirían. Para con esta información generar estrategias que ayuden a las marcas a llegarle a dicha generación de una forma exitosa y de acuerdo a sus necesidades particulares. A través de información recopilada en diferentes fuentes bibliográficas como revistas, periódicos, libros y diferentes estudios se plantearon una serie de objetivos que se enfocan en desarrollar estrategias que faciliten el diseño de campañas publicitarias de las organizaciones en la ciudad de Medellín dirigidas a los “millennials”. Luego de contar con toda la información necesaria, se realizó el proceso investigativo, donde se emplearon diferentes herramientas metodológicas como: observación, elaboración de entrevistas a profundidad, encuestas, análisis de anuncios publicitarios, sitios web de las marcas favoritas para los “millennials” y además entrevistas a expertos de dicha generación. Después de contar con toda la información necesaria, se procedió al análisis de resultados y la elaboración de estrategias para atraer la generación de los “millennials”, donde se encontraron los siguientes aspectos relevantes: los “millennials” buscan variedad de productos en la oferta, además la facilidad y disponibilidad para acceder a un punto de venta,la importancia de la red para comunicarse con la generación usando elementos tales como apps, redes sociales y páginas web, realizar eventos donde se vivan experiencias de marca, usar el Big Data para creación de campañas y nuevos productos, además de campañas creadas desde el neuromarketing especialmente desde la parte visual con diseños impactantes y creativos y particularmente apuntar a través de las campañas a la psicología de los “millennials” donde es importante conocer sus particularidades para generar un sentimiento más profundo de marca que motive a una futura compra. Como conclusión se encontró que los “millennials” son una generación hiperconectada, por lo tanto las páginas web y las redes sociales representan el canal de comunicación más usado para el contacto con las marcas. Además, las claves para generar un vínculo con estos son la generación de valor y la transmisión de valores, la primera mediante la oferta variada de productos, la disponibilidad de tiendas o puntos de compra y la oferta de promociones o descuentos. La segunda comunicando un estilo de vida con experiencias y grandes ideales, haciéndolo participe de las campañas.Satisfy millennials needs has become a big challenge for companies that every day find more demanding costumers and for brands is more difficult to establish loyalty with them. Therefore, it was decided to research the consumption patterns of the millennials of 4,5 and 6 strata in the city of Medellín, also which were the real reasons driving the purchase and the specific attributes that they look for in the products or services that they acquire. In order to generate strategies with this information that help brands to reach out to this generation successfully and according with them specific needs. Through collected information in different bibliographical sources such as magazines, newspapers, books and different studies a number of objectives that focus on developing strategies to facilitate the design of advertising campaigns of organizations in the city of Medellin aimed at " millennials " were set. After having all the necessary information was proceeded with the realization of the investigative process , where different methodological tools were used as : observation, developing depth interviews, surveys , analysis of advertisements , research of web sites of the favorite brands of millennials and also interviews with experts in that generation. Once all the necessary information was collected, it was continued with the analysis of results and the development of strategies to attract the "millennial" generation. The key points of these are the search of the "millennials” for the variety of products on offer, plus the ease and availability to access a point of sale. The importance of the network to communicate with the generation using elements such as “APP's”, social networks and web pages. Hold events where live brand experiences , use the " Big Data" for creating campaigns and new products , in addition to campaigns created from the neuromarketing especially from the part with striking visual and creative designs. In conclusion it was found that the millennials are hyperconected generation therefore web pages and social networks are the most used communication channel for contact with brands. Besides the keys to generate a link with these are value creation and transmission of values , the first by the wide range of products, availability of shops or points of purchase and offer promotions or discounts. The second communicating a lifestyle with experiences and great ideals, making them part of the campaigns