Los niños del reencuentro

El texto que presentaremos a continuación es un avance de la investigación en curso acerca de esta temática. Cuando iniciamos esta investigación partimos de ciertas premisas, y nos planteamos determinadas interrogantes como objetivos a demostrar. Definimos una estrategia que consideramos la más adecuada para el abordaje de un suceso histórico de características originales y de proyecciones políticas y sociales -en lo colectivo y en lo individual-; imprevisibles quizás, para quienes lo diseñaron y llevaron adelante, pero que se manifestaron con fuerza en el momento de su realización y que se prolongan en el presente. Analizamos el rol de la memoria como herramienta válida de reconstrucción e interpretación del pasado. Intentamos diferenciar cómo y cuándo se recuerda; cómo se determina la selección y jerarquización de los recuerdos por efecto del trascurso de la vida y de la Historia.Instituto de Investigaciones en Humanidades y Ciencias Sociales (IdIHCS

El viaje de los niños

En diciembre de 1983 llegaban a Uruguay 154 hijos de uruguayos exiliados. Este hecho inédito fue ideado y organizado por un grupo de uruguayos residentes en España y Uruguay y por españoles integrantes de organizaciones defensoras de los DDHH y del Gobierno español.Los uruguayos enviaron a sus hijos como avanzada de un próximo y certero desexilio. Los niños viajaban a un país en el cual sus padres corrían riesgo de ser apresados o secuestrados. Muchos de ellos eran hijos de presos políticos, desaparecidos oasesinados. Algunos incluso habían sufrido ellos mismos el secuestro o encarcelamiento junto a sus mayores, además de lo que implica en sí mismo el destierro en un niño.Para organizar este viaje trabajaron juntos los tres grupos que luego habrían de convivir en el país: exilio, inxilio y presos políticos. Es de destacar que la organización creada en Uruguay para ‘el viaje de los niños’ -la Comisión por el Reencuentro de los Uruguayos´ (CRU)-, logró ampliar sus objetivos primarios y a partir de 1985 amparó la salida de los presos políticos y la llegada de uruguayos a un país devastado por una crisis sin precedentes.Para esta investigación se ha relevado la prensa uruguaya e internacional; archivos, personales, estatales y de las organizaciones participantes y testimonios de los protagonistas

Los niños del reencuentro

El texto que presentaremos a continuación es un avance de la investigación en curso acerca de esta temática. Cuando iniciamos esta investigación partimos de ciertas premisas, y nos planteamos determinadas interrogantes como objetivos a demostrar. Definimos una estrategia que consideramos la más adecuada para el abordaje de un suceso histórico de características originales y de proyecciones políticas y sociales -en lo colectivo y en lo individual-; imprevisibles quizás, para quienes lo diseñaron y llevaron adelante, pero que se manifestaron con fuerza en el momento de su realización y que se prolongan en el presente. Analizamos el rol de la memoria como herramienta válida de reconstrucción e interpretación del pasado. Intentamos diferenciar cómo y cuándo se recuerda; cómo se determina la selección y jerarquización de los recuerdos por efecto del trascurso de la vida y de la Historia.Instituto de Investigaciones en Humanidades y Ciencias Sociales (IdIHCS

Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance

[Background & Aims]: Lipotoxicity triggers non-alcoholic fatty liver disease (NAFLD) progression owing to the accumulation of toxic lipids in hepatocytes including saturated fatty acids (SFAs), which activate pro-inflammatory pathways. We investigated the impact of hepatocyte- or circulating-derived small extracellular vesicles (sEV) secreted under NAFLD conditions on liver inflammation and hepatocyte insulin signalling. [Methods]: sEV released by primary mouse hepatocytes, characterised and analysed by lipidomics, were added to mouse macrophages/Kupffer cells (KC) to monitor internalisation and inflammatory responses. Insulin signalling was analysed in hepatocytes exposed to conditioned media from sEV-loaded macrophages/KC. Mice were i.v. injected sEV to study liver inflammation and insulin signalling. Circulating sEV from mice and humans with NAFLD were used to evaluate macrophage–hepatocyte crosstalk. [Results]: Numbers of sEV released by hepatocytes increased under NAFLD conditions. Lipotoxic sEV were internalised by macrophages through the endosomal pathway and induced pro-inflammatory responses that were ameliorated by pharmacological inhibition or deletion of Toll-like receptor-4 (TLR4). Hepatocyte insulin signalling was impaired upon treatment with conditioned media from macrophages/KC loaded with lipotoxic sEV. Both hepatocyte-released lipotoxic sEV and the recipient macrophages/KC were enriched in palmitic (C16:0) and stearic (C18:0) SFAs, well-known TLR4 activators. Upon injection, lipotoxic sEV rapidly reached KC, triggering a pro-inflammatory response in the liver monitored by Jun N-terminal kinase (JNK) phosphorylation, NF-κB nuclear translocation, pro-inflammatory cytokine expression, and infiltration of immune cells into the liver parenchyma. sEV-mediated liver inflammation was attenuated by pharmacological inhibition or deletion of TLR4 in myeloid cells. Macrophage inflammation and subsequent hepatocyte insulin resistance were also induced by circulating sEV from mice and humans with NAFLD. [Conclusions]: We identified hepatocyte-derived sEV as SFA transporters targeting macrophages/KC and activating a TLR4-mediated pro-inflammatory response enough to induce hepatocyte insulin resistance.This work was supported by grants PID2021-122766OB-I00 (AMV), PID2019-105989RB-I00 (JB), PID2020-113238RB-I00 (LB), PID2019-106581RB-I00 (MAM), PID2020-114148RB-I00 (MI), PID2019-107036RB-I00 (RF), and RD21/0006/0001 (ISCIII) (IL) funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación/10.13039/501100011033 and ERDF ‘A way of making Europe’ by the European Union (MICINN/AEI/FEDER, EU), grant EFSD/Boehringer Ingelheim European Research Programme on ‘Multi-System Challenges in Diabetes’ from the European Foundation for the Study of Diabetes (AMV), P2022/BMD-7227 (Comunidad de Madrid, Spain) (AMV), Fundación Ramón Areces (Spain) (AMV), CIBERdem (AMV and JB), CIBERhed (RF), and CIBERcv (LB) (ISCIII, Spain). LB and AMV belong to the Spanish National Research Council’s (CSIC’s) Cancer Hub. We also acknowledge the Spanish Ministry of Economy and Competitiveness (MINECO) postdoctoral contract IJCI-2015-24758 to IGM and the Spanish Ministry of Education, Culture and Sport (MECD) FPU17/02786 grant to RA

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Modelos parentales en el contexto urbano: un estudio exploratorio

El propósito de este trabajo es explorar las características que tienen las familias potosinas en cuanto a su cultura parental; es decir, explorar sus pautas de crianza, los diferentes vínculos de apego que se construyen y los patrones de éxito que se promueven para relacionarlos con sus características biográficas. El estudio se efectuó en la zona conurbada de San Luis Potosí (México), con la participación de 1008 familias de diferentes niveles culturales y se utilizó un instrumento de corte mediacional con 12 reactivos de carácter atribucional, que contempló la exploración de 4 modelos parentales. Los resultados arrojaron una preferencia de los padres por pautas de crianza negociadoras o rígidas, vínculos de apego cálidos o cercanos y patrones de éxito orientadores, encontrándose en menor medida las pautas de crianza indulgentes, los vínculos de apego elementales y los patrones de éxito promotores y emancipadores.The purpose of this study is to examine the characteristics of parenting culture in families from San Luis Potosí by exploring the orientations they follow in raising children, emotional ties and patterns of success, and associating them with biographical characteristics. The study was carried out in the metropolitan area of San Luis Potosí, Mexico, and 1,008 families with different levels of education participated. A mediational instrument with 12 attributional items was used to explore four parenting models. The results revealed parents’ preference for diplomatic or rigid orientations; strong, close emotional ties; and guiding patterns of success. Lenient child-raising orientations, basic emotional ties and encouraging and emancipatory success patterns were found to a lesser extent

Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition

9 páginas, 4 figuras, 2 tablas.The serine/threonine Pim 1 kinase is an oncogene whose expression is deregulated in several human cancers. Overexpression of Pim 1 facilitates cell cycle progression and suppresses apoptosis. Hence pharmacologic inhibitors of Pim 1 are of therapeutic interest for cancer. ETP-45299 is a potent and selective inhibitor of Pim 1 that inhibits the phosphorylation of Bad and 4EBP1 in cells and suppresses the proliferation of several non-solid and solid human tumor cell lines. The combination of the PI3K inhibitor GDC-0941 with ETP-45299 was strongly synergistic in MV-4-11 AML cells, indicating that the combination of selective Pim kinase inhibitors and PI3K inhibitor could have clinical benefit.Peer reviewe