Desarrollo de nuevas estrategias de vacunación frente el virus de la fiebre aftosa (VFA) basada en péptidos sintéticos

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 27-02-0

Interventions in intimate partner violence: A review of the literature

Introducción. La violencia de género es reconocida como problemática de salud pública a nivel mundial. La Organización Mundial de la Salud menciona que una de cada tres mujeres ha sido víctima de violencia de género y señala que el hogar se convierte en factor de riesgo para las mujeres, siendo ejercida en la mayoría de los casos por la pareja o ex pareja. Materiales y Método. Con el fin de conocer qué reporta la literatura acerca de las intervenciones frente a esta problemática, se hizo una revisión sistemática según criterios del Joanna Briggs Institute, identificando las dimensiones de abordaje de la violencia de género en pareja. Se recuperaron reportes de bases de datos científicas en el periodo de 2010 a 2019. De 103 que cumplían criterios de inclusión, y que mediante análisis de criterios de calidad según metodología Critical Appraisal Skills Programme Español -CASPe, se seleccionaron 24 estudios de Europa, Latinoamérica y África, de intervenciones en hombres, mujeres víctimas, pareja adulta, estudiantes y profesionales, con orientación psicoeducativa desde la perspectiva de género y el modelo piramidal. Resultados. Como dimensión común se identifica la reestructuración cognitiva orientada a las creencias culturalmente asociadas a los roles de género. Discusión y Conclusiones. Se resalta la efectividad a nivel de prevención y como principales limitaciones se describe el seguimiento de las intervenciones y el abordaje en parejas, lo cual plantea interrogantes del reconocimiento de las dinámicas de la violencia en ambos miembros y su red familiar.Magíster en Salud Mental ComunitariaMaestríaIntroduction. Gender violence is recognized as a public health problem worldwide. The World Health Organization mentions that one out of every three women has been a victim of gender violence and points out that the home becomes a risk factor for women, being exercised in most cases by the partner or ex-partner. Materials and Method. In order to know what the literature reports about interventions to address this problem, a systematic review was carried out according to the criteria of the Joanna Briggs Institute, identifying the dimensions of the approach to gender violence in couples. Reports were retrieved from scientific databases in the period from 2010 to 2019. From 103 that met inclusion criteria, and by means of quality criteria analysis according to Critical Appraisal Skills Programme Spanish -CASPe methodology, 24 studies were selected from Europe, Latin America and Africa, of interventions in men, female victims, adult couple, students and professionals, with psychoeducational orientation from the gender perspective and the pyramidal model. Results. Cognitive restructuring oriented to beliefs culturally associated to gender roles is identified as a common dimension. Discussion and Conclusions. The effectiveness at the level of prevention is highlighted and the main limitations are described as the follow-up of interventions and the approach in couples, which raises questions about the recognition of the dynamics of violence in both members and their family network

Bovine gammadelta T Cells Are a Major Regulatory T Cell Subset

In humans and mice, γδ T cells represent <5% of the total circulating lymphocytes. In contrast, the γδ T cell compartment in ruminants accounts for 15–60% of the total circulating mononuclear lymphocytes. Despite the existence of CD4(+)CD25(high) Foxp3(+) T cells in the bovine system, these are neither anergic nor suppressive. We present evidence showing that bovine γδ T cells are the major regulatory T cell subset in peripheral blood. These γδ T cells spontaneously secrete IL-10 and proliferate in response to IL-10, TGF-β, and contact with APCs. IL-10–expressing γδ T cells inhibit Ag-specific and nonspecific proliferation of CD4(+) and CD8(+) T cells in vitro. APC subsets expressing IL-10 and TFG-β regulate proliferation of γδ T cells producing IL-10. We propose that γδ T cells are a major regulatory T cell population in the bovine system

Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway

Dendritic cells (DC) are central to the initiation of immune responses, and various approaches have been used to target vaccines to DC in order to improve immunogenicity. Cannulation of lymphatic vessels allows for the collection of DC that migrate from the skin. These migrating DC are involved in antigen uptake and presentation following vaccination. Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B–Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B–Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed

Intervenções sobre a violência entre parceiros íntimos: Uma Artigo da Revisão da Literatura

Introduction: Intimate partner violence is recognized as a public health problem. The World Health Organization reports that one out of three women has been a victim of intimate partner violence in the home, being mostly perpetrated by a current or former intimate partner. This type of violence is referred to as intimate partner violence, which is the purpose of this review. Materials and Methods: A literature review was conducted following the Joanna Brigs Institute’s criteria to synthesize knowledge on the intervention type reported so far. A search was conducted using standardized terms in indexed databases between 2010 and 2019, returning 103 articles after applying the quality criteria analysis according to the Critical Appraisal Skills Programme methodology in Spanish. Results: 24 articles from Europe, Latin America and Africa were selected, in which gender-based psychoeducational interventions have been mainly reported as well as the pyramid model made with men, women victims and adult couples, also adolescents and professionals. Psychoeducation was aimed to reflect on cultural beliefs associated with gender roles. Conclusions: The effectiveness of prevention interventions is evident. Follow-up on couple interventions and their implementation are reported to be the main limitations, which raises questions about the recognition of intimate partner violence dynamics and support network. How to cite this article: &nbsp;Salas-Cubillos Nathaly, García Charry Viviana C, Zapata-Losada Leydy V, Díaz-Usme Olga S. Intervenciones en violencia de género en pareja: Articulo de Revisión de la Literatura. Revista Cuidarte. 2020;11(3):e980. http://dx.doi.org/10.15649/cuidarte.980 &nbsp;Introducción: La violencia &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;es reconocida, como problemática de salud pública. La Organización Mundial de la Salud señala que una de cada tres mujeres ha sido víctima de violencia y que esta se presenta al interior del hogar siendo ejercida en la mayoría de los casos por la pareja o ex pareja, &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;se alude a la violencia de género al interior de la relación de pareja, propósito de esta revisión. &nbsp;Materiales y Métodos: Revisión de la literatura según criterios del Joanna Briggs Institute, con el objetivo de sintetizar el conocimiento relacionado con los tipos de intervención reportados. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Se realizó la búsqueda con términos normalizados en bases de datos indexadas periodo 2010 a 2019, que arrojo 103 artículos. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Posterior al análisis de criterios de calidad según metodología Critical Appraisal Skills Programme Español &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Resultados: Se seleccionaron 24 originados en Europa, Latinoamérica y África. Reportan principalmente intervenciones a nivel de psicoeducación desde la perspectiva de género y el modelo piramidal realizadas con hombres, mujeres víctimas y parejas adultas, así como con adolescentes y profesionales. La psico educación se orientó a reflexionar sobre las creencias culturalmente asociadas a los roles de género. Conclusiones: Se resalta la efectividad de las intervenciones a nivel de prevención y como principales limitaciones se describe el seguimiento y la dificultad para realizar intervenciones con la pareja, lo cual plantea interrogantes acerca del reconocimiento de las dinámicas de violencia en la pareja y su red de apoyo. Como citar este artículo: &nbsp;Salas-Cubillos Nathaly, García Charry Viviana C, Zapata-Losada Leydy V, Díaz-Usme Olga S. Intervenciones en violencia de género en pareja: Articulo de Revisión de la Literatura. Revista Cuidarte. 2020;11(3):e980. http://dx.doi.org/10.15649/cuidarte.980 &nbsp; &nbsp;Introdução: A violência entre parceiros íntimos é reconhecida como um problema de saúde pública. A Organização Mundial da Saúde informa que uma de cada três mulheres foi vítima de violência por parceiro íntimo no lar, sendo a maioria perpetrada por um atual ou antigo parceiro íntimo. Este tipo de violência é chamado de violência do parceiro íntimo, que é o objetivo desta revisão. Materiais e Métodos: Uma revisão bibliográfica foi realizada seguindo os critérios do Instituto Joanna Brigs para sintetizar o conhecimento sobre o tipo de intervenção relatado até o momento. Foi realizada uma pesquisa usando termos padronizados em bancos de dados indexados entre 2010 e 2019, retornando 103 artigos após a aplicação da análise dos critérios de qualidade de acordo com a metodologia do Programa de Habilidades de Avaliação Crítica em espanhol. Resultados: 24 artigos da Europa, América Latina e África foram selecionados, nos quais intervenções psico-educacionais baseadas no gênero foram relatadas principalmente, bem como o modelo piramidal feito com homens, mulheres vítimas e casais adultos, também adolescentes e profissionais. A psicoeducação teve como objetivo refletir sobre as crenças culturais associadas aos papéis de gênero. Conclusões: A eficácia das intervenções de prevenção é evidente. O acompanhamento das intervenções de casal e sua implementação são relatados como as principais limitações, o que levanta questões sobre o reconhecimento da dinâmica da violência por parceiro íntimo e da rede de apoio. Como citar este artigo &nbsp;Salas-Cubillos Nathaly, García Charry Viviana C, Zapata-Losada Leydy V, Díaz-Usme Olga S. Intervenciones en violencia de género en pareja: Articulo de Revisión de la Literatura. Revista Cuidarte. 2020;11(3):e980. http://dx.doi.org/10.15649/cuidarte.980 &nbsp; &nbsp

Upregulated proteasome subunits in COVID-19 patients: a link with hypoxemia, lymphopenia and inflammation

Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expressionThis research was funded by Health Research Fund (Fondo de Investigación Sanitario [FIS])-European Regional Development Fund (FEDER), Spain through PI19/01612 (F.G.-R.) and COV20/00207 and PI19-01363 (C.C.-Z.) and ISCIII (CP18/00028), co-funded by ESF, “Investing in your future

NLRP3 Inflammasome Overactivation in Patients with Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1β, IL-18, gasdermin D, and tissue factor. Although further research is needed, we propose that serum tissue factor concentration might be a useful prognosis biomarker for clinical outcome, and for Tako-Tsubo cardiomyopathy and cerebral vasospasm prediction. Remarkably, MCC-950 inhibitor effectively blocks NLRP3 activation in aSAH monocyte culture and supresses tissue factor release to the extracellular space. Finally, our findings suggest that NLRP3 activation could be due to the release of erythrocyte breakdown products to the subarachnoid space during aSAH event. These data define NLRP3 activation in monocytes from aSAH patients, indicating systemic inflammation that results in serum TF upregulation which in turns correlates with aSAH severity and might serve as a prognosis biomarker for aSAH clinical outcome and for cerebral vasospasm and Tako-Tsubo cardiomyopathy prediction.This work was supported by the following fundings: Fondo de Investigación Sanitario (FIS)-Fondos FEDER, Spain: PI19/01612 (F.G-R.) and CP18/00028 and PI19-01363 (C.C-Z.

A system dynamics model to predict the human monocyte response to endotoxins

System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs) induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα), which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET). The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C-C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsisThis work was supported by grants from the “Instituto de Salud Carlos III” (ISCiii), “Fondo de Investigación Sanitaria” (FIS), and Fondos FEDER (PI14/01234, PIE15/00065) to EL-C. EA work contract is supported by the Torres Quevedo program from “Ministerio de Economía y Competitividad” (SPTQ1300X006175XV0). VT work contract is supported by the “Ministerio de Economía y Competitividad” (PTA2013-8265-I

Obesity attenuates the effect of sleep apnea on active TGF-ss 1 levels and tumor aggressiveness in patients with melanoma

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients