Evaluation of the anti-angiogenic potential of hydroxytyrosol derivatives

Angiogenesis, a process which allows the formation of new vessels from pre-existing ones, is an essential phenomenon for tumor survival since it allows cancer cells to obtain nutrients and oxygen. This explains the increasing interest showed by many groups of research and pharmaceutical companies to find compounds with potential to disrupt at least one of the steps within the angiogenic process. Hydroxytyrosol (3,4-dihydroxyphenyl ethanol) has been identified as the most important health-related phenolic compound of virgin olive oil because of its pleiotropic effects on multiple targets. In 2012, our group identified hydroxytyrosol as an anti-angiogenic compound able to inhibit several key steps in the angiogenic process. In the present study, the potential effects of six hydroxytyrosol derivatives are tested and compared with those exhibited by hydroxytyrosol by making use of several in vitro and in vivo assays. Results indicate that these are candidate new anti-angiogenic compounds with potential utility in anti-tumor and anti-angiogenic therapies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communication has the support of a travel grant

PLANEACIÓN DIDÁCTICA

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

TOMA DE DECISIONES BASADAS EN EL ALGORITMO DE DIJKSTRA

Una de las funciones que realiza un ‘Radio Cognitivo’ es la toma de decisiones sobre el espectro radioeléctrico, esto a partir del análisis que realiza de su entorno. En este trabajo de investigación, se propone un método para la toma de decisiones para la selección de una banda en el espectro radioeléctrico que cumpla con ciertos criterios requeridos para una aplicación. Esta toma de decisiones se basa en un algoritmo de búsqueda del camino más corto similar al Algoritmo de Dijkstra. Para encontrar el camino más corto, el cual representa a la banda de frecuencia requerida, se especifican los atributos o parámetros a considerar para cada una de las bandas de acuerdo a una aplicación en particular o servicio requerido. A estos atributos o parámetros se les asignan valores es decir, pesos que determinan la prioridad e importancia para cada servicio. El algoritmo propuesto basado en Dijkstra, evalúa los parámetros del conjunto de bandas disponibles considerando el peso asignado, e indica la banda a seleccionar y que cubre con los criterios de la toma de decisiones. Se realizaron simulaciones por computadora para caracterizar los servicios identificados como mejor esfuerzo ‘Best Effort’ y tiempo real ‘Real Time’, obteniendo como resultado una latencia reducida que representa un tiempo práctico para ser implementado en un Radio Cognitivo en su toma de decisiones. Se observó también que los tiempos mostraron una mejora al ser comparados con los resultados obtenidos al implementar el Algoritmo de AHP

Multi-antibiotic resistant bacteria in landfill bioaerosols: environmental conditions and biological risk assessment

Landfills, as well as other waste management facilities are well-known bioaerosols sources. These places may foment antibiotic-resistance in bacterial bioaerosol (A.R.B.) due to inadequate pharmaceutical waste disposal. This issue may foster the necessity of using last-generation antibiotics with extra costs in the health care system, and deaths. The aim of this study was to reveal the multi-antibiotic resistant bacterial bioaerosol emitted by a sanitary landfill and the surrounding area. We evaluated the influence of environmental conditions in the occurrence of A.R.B. and biological risk assessment. Antibiotic resistance found in the bacteria aerosols was compared with the AWaRE consumption classification. We used the BIOGAVAL method to assess the workers' occupational exposure to antibiotic-resistant bacterial bioaerosols in the landfill. This study confirmed the multi-antibiotic resistant in bacterial bioaerosol in a landfill and in the surrounding area. Obtained mean concentrations of bacterial bioaerosols, as well as antibiotic-resistant in bacterial bioaerosol (A.R.B.), were high, especially for fine particles that may be a threat for human health. Results suggest the possible risk of antibiotic-resistance interchange between pathogenic and non-pathogenic species in the landfill facilities, thus promoting antibiotic multi-resistance genes spreading into the environment

Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection

Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated production of PsaA displayed on PHB inclusions in recombinant Escherichia coli. This suggested that the PsaA fusion to the PHB synthase did not interfere with PHB synthase activity and its ability to mediate formation of nano-sized inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA. Isolated PHB beads showed a negative surface charge. Transmission electron microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE, tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1 titer were similar between soluble and insoluble PsaA, the IgG2 titers were strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in whole cell lysates of seven different serotypes of S. pneumoniae. This study suggested that PHB beads are suitable carriers for PsaA in order to induce a significant and specific Th-2-type immune response

LITERATURA

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

Family centered decision making in advanced chronic kidney disease. From individual autonomy to family or community autonomy

El aumento de la tasa de incidencia y prevalencia de la enfermedad renal crónica plantea desafíos y dilemas éticos que tanto pacientes como familiares y profesionales de salud deben enfrentar diariamente. El objetivo de este artículo es presentar una reflexión sobre la manera como, para la toma decisiones, los pacientes recurren a terceros como partícipes, lo que requeriría un abordaje desde la autonomía solidaria. Se presenta el análisis de doce entrevistas semiestructuradas, realizadas a pacientes de 60 años o más, de distintos programas de la Unidad de Nefrología del Hospital Universitario San Ignacio, Colombia, entre 20172018. En este artículo se propone la necesidad de toma de decisiones centradas en la familia de los pacientes con enfermedades crónicas, antes de que su estado sea avanzado y los estados de inconsciencia impidan su autodeterminación, considerando la determinación social de la autonomía.Q4Q4The increase in the incidence and prevalence rate of Chronic Kidney Disease poses challenges and ethical dilemmas that patients, family members and health professionals must face daily. The objective of this article is to present a reflection on the way in which patients make recourse to third parties as participants in their decision-making, which would require an approach based on solidarity autonomy. The analysis of twelve semi-structured interviews conducted with patients 60 years of age and older, from different programs of the Nephrology Unit of the Hospital Universitario San Ignacio in the period 2017-2018 Colombia, is presented. This article proposes the need for family-centered decision making of patients with chronic diseases, before their state is advanced and states of unconsciousness prevent their self-determination, considering the social determination of autonomy.Revista Internacional - Indexad

ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA

Circulating tumour DNA; Pancreatic cancer; Tumour evolutionADN tumoral circulant; Càncer de pàncrees; Evolució tumoralADN tumoral circulante; Cáncer de páncreas; Evolución tumoralBackground Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution. Methods To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. Results SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. Conclusions This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.This work was supported by the European Research Council (ERC) no. 670582 (Call: ERC-2014-ADG) to Dr. Hidalgo. R.A.T is supported by the Miguel Servet-II Research Award and the 2021 call for Proyectos de generación de conocimiento by the Institute of Health Carlos III (ISCIII) of the Ministry of Economy [CP17/00199], the Olga Torres Foundation Award to emerging researchers [2017, to R.A.T, 2601], and received research grants from Novartis, Astrazeneca, and Beigene pharmaceuticals, not related to this study. N.M is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (Grant Number 211179/Z/18/Z), and also receives funding from Cancer Research UK Lung Cancer Centre of Excellence, Rosetrees, and the NIHR BRC at University College London Hospitals

Estudio fitoquímico y evaluación de la capacidad antioxidante de flores de Senna spectabilis obtenidas en la región andina colombiana

The present work shows the results of the phytochemical study of Senna spectabilis flowers and the evaluation of their antioxidant capacity, for this, the plant material was collected in the municipality of Guaduas (Cundinamarca) and identified through the Colombian National Herbarium with the number collection COL 600165, after extraction processes by cold maceration, 100 g of ethanolic extract were obtained, which was fractionated with solvents of increasing polarity, obtaining fractions of heptane, dichloromethane and ethyl acetate, then they were subjected to separation processes by Thin layer chromatography (TLC) and column chromatography (CC), the tentative identification of the obtained mixtures and isolated compounds was carried out by gas chromatography coupled to mass spectrometry (GC-MS), allowing the identification of three mixtures made up of ester, ketone, anthraquinone, monoterpenoid and a derivative of cinnamic acid compounds; and the compounds methyl cinnamate and caffeine. The antioxidant capacity of the obtained fractions and the ethanolic extract were studied by the DPPH method, in addition, the measurement of total phenols and the quantification of flavonoids were carried out. The results indicate that the dichloromethane fraction exhibited an inhibition percentage greater than 30 % and that the highest concentration of phenols and flavonoids is found in this same fraction. In this way, the work gave a chemical contribution (isolation of methyl cinnamate and caffeine, and three mixtures) and a biological contribution after identifying the fraction of dichloromethane obtained from the flowers of the species as the one with the greatest amount of substances with antioxidant capacity. has respect to the other fractions and extracts.El presente trabajo muestra los resultados del estudio fitoquímico de las flores de Senna spectabilis y la evaluación de su capacidad antioxidante, para esto se recolectó el material vegetal en el municipio de Guaduas (Cundinamarca) y se identificó a través del Herbario Nacional Colombiano con el número de colección COL 600165; tras procesos de extracción por maceración en frío se obtuvieron 100 g de extracto etanólico, el cual fue fraccionado con solventes de polaridad creciente, obteniéndose fracciones de heptano, diclorometano y acetato de etilo, estas fueron sometidas a procesos de separación por cromatografía en capa fina (CCF) y cromatografía en columna (CC), la identificación tentativa de las mezclas obtenidas y los compuestos aislados se llevó a cabo mediante cromatografía de gases acoplada a espectrometría de masas (CG-EM), permitiendo identificar tres mezclas conformadas por compuestos tipo éster, cetona, antraquinona, monoterpenoide y un derivado del ácido cinámico, y los compuestos cinamato de metilo y cafeína. Se estudió la capacidad antioxidante de las fracciones obtenidas y el extracto etanólico por el método DPPH, además se realizó la medición de fenoles totales y la cuantificación de flavonoides. Los resultados indican que la fracción de diclorometano exhibió un porcentaje de inhibición superior a 30 % y que la mayor concentración de fenoles y flavonoides se encuentra en esta misma fracción. De esta manera, el trabajo dio un aporte químico (aislamiento de cinamato de metilo y cafeína, y tres mezclas) y un aporte biológico, tras identificar a la fracción de diclorometano obtenida de las flores de la especie como la que mayor cantidad de sustancias con capacidad antioxidante tiene respecto a otras fracciones y otros extractos

Digital Inclusion Across the Americas and Caribbean

This research brings together digital inequality scholars from across the Americas and Caribbean to examine efforts to tackle digital inequality in Uruguay, Chile, Peru, Brazil, Mexico, Cuba, Jamaica, the United States, and Canada. As the case studies show, governmental policy has an important role to play in reducing digital disparities, particularly for potential users in rural or remote areas, as well as populations with great economic disparities. We find that public policy can effectively reduce access gaps when it combines the trifecta of network, device, and skill provision, especially through educational institutions. We also note, that urban populations have benefitted from digital inclusion strategies to a greater degree. This underscores that, no matter the national context, rural-urban digital inequality (and often associated economic inequality) is resistant to change. Even when access is provided, potential users may not find it affordable, lack skills, and/or see no benefit in adoption. We see the greatest potential for future digital inclusion in two related approaches: 1) initiatives that connect with hard-to-reach, remote, and rural communities outside urban cores and 2) initiatives that learn from communities about how best to provide digital resources while respecting their diversely situated contexts, while meeting social, economic and political needs