Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma

Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by highresolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum-derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic-based study aimed at characterizing exosomes derived from melanoma CSCs and patients’ serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.MICIU FPU15/03682 FPU15/02350Ministerio de Ciencia, Innovación y Universidades (MICIU) MAT2015-62644.C2.2.R RTI2018-101309-BC2Instituto de Salud Carlos III PIE16-00045Junta de Andalucía SOMM17/6109/UGR (UCE-PP2017-3)European Union (EU) SOMM17/6109/UGR (UCE-PP2017-3)Chair 'Doctors Galera-Requena in cancer stem cell research' CMC-CTS963Fundación MEDIN

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Ecos de la academia: Revista de la Facultad de Educación, Ciencia y Tecnología - FECYT Nro 6

Ecos de la academia, Revista de la Facultad de Educación Ciencia y Tecnología es una publicación científica de la Universidad Técnica del Norte, con revisión por pares a doble ciego que publica artículos en idioma español, quichua, portugués e inglés. Se edita con una frecuencia semestral con dos números por año.En ella se divulgan trabajos originales e inéditos generados por los investigadores, docentes y estudiantes de la FECYT, y contribuciones de profesionales de instituciones docentes e investigativas dentro y fuera del país, con calidad, originalidad y relevancia en las áreas de ciencias sociales y tecnología aplicada.Modelos multidimensionales del bienestar en contextos de enseñanza- aprendizaje: una revisión sistemática. Nuevas tendencias para el área académica de la Publicidad en la zona 1 del Ecuador. Propuesta de un curso de escritura académica bajo la base de modelos experienciales. Aproximación al estudio de las emociones. Seguimiento a egresados y graduados para actualizar el perfil de egreso y profesional. Impacto de la Gerencia de Calidad en el clima organizacional en Educación Básica. Comunicación efectiva del gerente educativo orientada al manejo de conflictos en el personal docente. Meritocracia: Democratización o exclusión en el acceso a la educación superior en Ecuador. Asertividad y desempeño académico en estudiantes universitarios. La creatividad en la formación profesional. Aspectos metodológicos en el proceso de enseñanza- aprendizaje de la gimnasia en estudiantes de Educación Física. English Language Learning Interaction through Web 2.0 Technologies. La sistematización de la práctica educativa y su relación con la metodología de la investigación. El ozono y la oxigenación hiperbárica: una vía para mejorar la recuperación en lesiones deportivas. La labor tutorial: Independencia del aprendizaje en el contexto universitario. Motivación hacia la profesión docente en la Enseñanza Secundaria. El uso académico de Facebook y WhatsApp en estudiantes universitarios... La educación superior en Ecuador: situación actual y factores de mejora de la calidad. El Proyecto de Investigación “Imbabura Étnica”

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

¿Predice el Kidney Donor Profile Index (KDPI) la supervivencia del injerto y del paciente en una población española?

Resumen: Antecedentes y objetivo: El Kidney Donor Profile Index (KDPI), junto a otras variables del donante y receptor, puede optimizar el proceso de asignación de órganos. Este estudio tiene como objetivo comprobar la aplicabilidad del KDPI en una población española, así como su capacidad de predicción de la supervivencia del injerto y del paciente. Materiales y métodos: Se estudiaron 2.734 trasplantes renales llevados a cabo en Andalucía entre enero de 2006 y diciembre de 2015. Los casos se agruparon por edad del receptor y cuartil del KDPI y se compararon entre grupos tanto la supervivencia del injerto como la del paciente. Resultados: El KDPI discrimina con precisión los órganos óptimos de los subóptimos o marginales. Para receptores entre 18 y 59 años presenta un hazard ratio de 1,013 (p < 0,001) para supervivencia de injerto censurada para muerte y de 1,013 (p = 0,007) para supervivencia del paciente. Para receptores mayores de 60 años el hazard ratio es de 1,016 (p = 0,001) para supervivencia del injerto censurada para muerte y de 1,011 (p = 0,007) para supervivencia del paciente. Un análisis multivariante identificó como factores predictivos de la supervivencia del injerto el KDPI, la edad del donante, la donación tras muerte circulatoria, la edad y el sexo del receptor. Conclusiones: El KDPI permite relacionar, a grandes rasgos, las características del donante con la mayor o menor supervivencia del injerto y del paciente en la población española. No obstante, debido a ciertas limitaciones, convendría elaborar un índice propio a partir de los datos españoles o europeos. En este trabajo se identifican algunos factores predictivos de la supervivencia del injerto que pueden servir como primer paso en esa línea. Abstract: Background and objective: The Kidney Donor Profile Index (KDPI), together with other donor and recipient variables, can optimise the organ allocation process. This study aims to check the feasibility of the KDPI for a Spanish population and its predictive ability of graft and patient survival. Materials and methods: Data from 2,734 kidney transplants carried out in Andalusia between January 2006 and December 2015 were studied. Cases were grouped by recipient age, categorised by KDPI quartile and both graft and patient survival were compared among groups. Results: The KDPI accurately discriminated optimal organs from suboptimal or marginal ones. For adult recipients (aged: 18-59 years) it presents a hazard ratio of 1.013 (P < .001) for death-censored graft survival and of 1.013 (P = .007) for patient survival. For elderly recipients (aged: 60+ years), KDPI presented a hazard ratio of 1.016 (P = .001) for death-censored graft survival and of 1.011 (P = .007) for patient survival. A multivariate analysis identified the KDPI, donor age, donation after circulatory death, recipient age and gender as predictive factors of graft survival. Conclusions: The results obtained show that the KDPI makes it possible to relate the donor's characteristics with the greater or lesser survival of the graft and the patient in the Spanish population. However, due to certain limitations, a new index for Spain based on Spanish or European data should be created. In this study, some predictive factors of graft survival are identified that may serve as a first step in this path. Palabras clave: Trasplante renal, Supervivencia del injerto, Análisis de supervivencia, KDPI, Keywords: Kidney transplantation, Graft survival, Survival analysis, KDP

Does the Kidney Donor Profile Index (KDPI) predict graft and patient survival in a Spanish population?

Background and objective: The Kidney Donor Profile Index (KDPI), together with other donor and recipient variables, can optimise the organ allocation process. This study aims to check the feasibility of the KDPI for a Spanish population and its predictive ability of graft and patient survival. Materials and methods: Data from 2734 kidney transplants carried out in Andalusia between January 2006 and December 2015 were studied. Cases were grouped by recipient age, categorised by KDPI quartile and both graft and patient survival were compared among groups. Results: The KDPI accurately discriminated optimal organs from suboptimal or marginal ones. For adult recipients (aged: 18–59 years) it presents a hazard ratio of 1.013 (P < 0.001) for death-censored graft survival and of 1.013 (P = 0.007) for patient survival. For elderly recipients (aged: 60+ years), KDPI presented a hazard ratio of 1.016 (P = 0.001) for death-censored graft survival and of 1.011 (P = 0.0007) for patient survival. A multivariate analysis identified the KDPI, donor age, donation after circulatory death, recipient age and gender as predictive factors of graft survival. Conclusions: The results obtained show that the KDPI makes it possible to relate the donor's characteristics with the greater or lesser survival of the graft and the patient in the Spanish population. However, due to certain limitations, a new index for Spain based on Spanish or European data should be created. In this study, some predictive factors of graft survival are identified that may serve as a first step in this path. Resumen: Antecedentes y objetivo: El Kidney Donor Profile Index (KDPI), junto a otras variables del donante y receptor, puede optimizar el proceso de asignación de órganos. Este estudio tiene como objetivo comprobar la aplicabilidad del KDPI en una población española, así como su capacidad de predicción de la supervivencia del injerto y del paciente. Materiales y métodos: Se estudiaron 2.734 trasplantes renales llevados a cabo en Andalucía entre enero de 2006 y diciembre de 2015. Los casos se agruparon por edad del receptor y cuartil del KDPI y se compararon entre grupos tanto la supervivencia del injerto como la del paciente. Resultados: El KDPI discrimina con precisión los órganos óptimos de los subóptimos o marginales. Para receptores entre 18 y 59 años presenta un hazard ratio de 1,013 (p < 0,001) para supervivencia de injerto censurada para muerte y de 1,013 (p = 0,007) para supervivencia del paciente. Para receptores mayores de 60 años el hazard ratio es de 1,016 (p = 0,001) para supervivencia del injerto censurada para muerte y de 1,011 (p = 0,007) para supervivencia del paciente. Un análisis multivariante identificó como factores predictivos de la supervivencia del injerto el KDPI, la edad del donante, la donación tras muerte circulatoria, la edad y el sexo del receptor. Conclusiones: El KDPI permite relacionar, a grandes rasgos, las características del donante con la mayor o menor supervivencia del injerto y del paciente en la población española. No obstante, debido a ciertas limitaciones, convendría elaborar un índice propio a partir de los datos españoles o europeos. En este trabajo se identifican algunos factores predictivos de la supervivencia del injerto que pueden servir como primer paso en esa línea. Keywords: Kidney transplantation, Graft survival, Survival analysis, KDPI, Palabras clave: Trasplante renal, Supervivencia del injerto, Análisis de supervivencia, KDP

Viejos problemas, nuevas alternativas : estrategias de lucha contra la pobreza gestadas desde el Sur

Este libro reúne un conjunto de trabajos presentados en el Seminario Internacional "Estrategias contra la pobreza: alternativas desde el Sur" organizado conjuntamente por el Programa CLACSO-CROP de estudios sobre pobreza en América Latina y el Caribe y el Centro de Estudios sobre Población, Empleo y Desarrollo (CEPED, Facultad de Ciencias Económicas de la Universidad de Buenos Aires) en diciembre de 2009. En los textos se realiza un balance de las respuestas surgidas, tanto desde el Estado como desde los diferentes grupos de la sociedad civil, ante el incre- mento de la marginalidad, la pobreza y la exclusión, resultantes de los proce- sos de achicamiento del Estado, la desprotección laboral y el aumento del desempleo. En general, las miradas son críticas cuando se trata de analizar las políticas que se llevaron a cabo en los distintos países del continente bajo el marco ideológico de los organismos internacionales. Los autores muestran que, en general, éstas no estuvieron orientadas a atacar las causas de tales procesos, sino que por el contrario profundizaron aún más la situación agre- gando "carga a la carga" y aumentando los niveles de vulnerabilidad social. Otro conjunto de artículos, por su parte, rescatan el surgimiento de propuestas alternativas generadas por movimientos sociales y comunitarios autogestionados, movilizados en defensa del territorio, de sus derechos o en demanda de trabajo. Estas experiencias organizadas "desde abajo" y a partir de la propia voluntad de los interesados han dado origen a formas novedosas y alternativas de posicionarse en los diversos contextos, aunque con distintos alcances y logros. Finalmente, dos capítulos abordan la problemática desde un orden teórico- metodológico en los que se discute conceptualmente la noción de pobreza y desigualdad y las posibilidades de incidencia de los grupos subalternos; y otro donde se considera la posibilidad de realizar mediciones cuantitativas en relación a la pobreza y la riqueza. Es a partir de esta diversidad de cuestiones, por su origen y envergadura, que se configuran las "alternativas desde el Sur"

Efficacy and safety of a comprehensive educational antimicrobial stewardship program focused on antifungal use

[Objective] Few data exist regarding the impact of antimicrobial stewardship programs on antifungal use. We evaluated the efficacy and safety of a comprehensive long-term antimicrobial stewardship program (ASP) focused on antifungal use.[Methods] During a 9-year period, we quarterly assessed antifungal consumption, incidence density of hospital-acquired candidemia, Candida spp. distribution, antifungal resistance, and crude death rate per 1000 occupied bed days (OBDs) of hospital-acquired candidemia. We performed segmented regression analysis of interrupted time series.[Results] A significant change in trend was observed for antifungal consumption, with a sustained reduction of -0.87% per quarter (95% confidence interval [CI], −1.36 −0.38, p < 0.001), accounting for a final reduction of −38.4%. The main reduction was produced in fluconazole, with a sustained reduction of −1.37% per quarter (95%CI, −1.96 −0.68, p<0.001). The incidence density of hospital-acquired candidemia decreased, with a change in slope of −5.06% cases per 1000 OBDs per year (95%CI, −8.23 −1.77, p = 0.009). The 14-day crude death rate per 1000 OBDs dropped from 0.044 to 0.017 (−6.36% deaths per 1000 OBDs per year; 95%CI, −13.45 −1.31, p = 0.09).[Conclusions] This ASP has succeeded in optimizing the use of antifungal with a long-lasting reduction without increasing the incidence, neither the mortality, of hospital-acquired candidemia.The program received public funding from the Regional Health Ministry of Andalucía (Grant PI-0361-2010), which did not participate in the development of the program or the analysis of its results