Bioactive Food Compounds As Epigenetic Regulators

Introduction: Nutrigenomics explores and defines the rapidly evolving field of interactions in the diet and genome, through the use of nutrition, proteomics, physiology, biochemistry and epigenomics to seek and explain the mutual interactions between genes and nutrients from a molecular approach. Objective: To summarize the evidence of the impact that bioactive compounds of food exerts on epigenetic events aimed primarily at disease prevention. Methods: A literature review was carried out on the main bioactive compounds of food as epigenetic regulators, in the following search engines: COCHRANE, PUBMED, MEDLINE, LILACS, SCIELO, CINAHL, EBSCO and SCOPUS. The synthetic analytical method was used. Results: 40 bibliographic sources were found, of which 33 scientific articles were used that provided relevant information on the subject and seven articles were excluded. Discussion: There is scientific evidence about various bioactive compounds that experience efficacy in disease prevention through epigenetic regulation. Conclusion: With the continuous progress of changes in lifestyle, it is necessary to study new molecules, which can potentially be used for disease prevention and find new drugs that can be crucial in the treatment of different diseases. Keywords: bioactive, food, regulators, epigenetics. RESUMEN Introducción: La nutrigenómica explora y define el campo en rápida evolución de las interacciones en la dieta y el genoma, mediante el uso de la nutrición, proteómica, fisiología, bioquímica y epigenómica para buscar y explicar las mutuas interacciones existentes entre genes y nutrientes desde un enfoque molecular. Objetivo: Resumir la evidencia del impacto que ejercen los compuestos bioactivos de los alimentos sobre los eventos epigenéticos dirigido principalmente en la prevención de enfermedades. Métodos: Se realizó una revisión bibliográfica acerca de los principales compuestos bioactivos de los alimentos como reguladores epigenéticos, en los siguientes buscadores: COCHRANE, PUBMED, MEDLINE, LILACS, SCIELO, CINAHL, EBSCO y SCOPUS. Se empleó el método analítico sintético. Resultados: Se encontraron 40 fuentes bibliográficas, de los cuales se utilizaron 33 artículos científicos que aportaron información relevante del tema y se excluyeron siete artículos. Discusión: Existe evidencia científica acerca de diversos compuestos bioactivos que demuestran eficacia en la prevención de enfermedades mediante la regulación epigenética. Conclusiones: Con el avance continuo de los cambios en el estilo de vida, es necesario estudiar nuevas moléculas, que pueden usarse potencialmente para la prevención de enfermedades y encontrar nuevos medicamentos que pueden ser cruciales en el tratamiento de distintas enfermedades. Palabras clave: bioactivos, alimentos, reguladores, epigenética

A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains

Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34+ fetal cord blood from a single donor. Our results showed that all murine strains sustained human immune cells within a proinflammatory environment induced by GvHD. However, the Hu-SGM3 model consistently generated higher numbers of human T cells, monocytes, dendritic cells, mast cells, and megakaryocytes, and a low number of circulating platelets showing an activated profile when compared with the other murine strains. The hu-NOG-EXL model had a similar cell development profile but a higher number of circulating platelets with an inactivated state, and the hu-NSG and hu-NCG developed low frequencies of immune cells compared with the other models. Interestingly, only the hu-SGM3 and hu-EXL models developed mast cells. In conclusion, our findings highlight the importance of selecting the appropriate humanized mouse model for specific research questions, considering the strengths and limitations of each model and the immune cell populations of interest. © 2023 by the authors

Diagnóstico diferencial de dengue y chikungunya en pacientes pediátricos

Introduction: Dengue and Chikungunya infections have similar clinical symptoms, which makes their clinical diagnosis complex. Moreover, both are transmitted by the same mosquito vectors, which results in virus co-circulation and co-infection. However, the outcome of these diseases differs: Chikungunya fever is rarely fatal but can have permanent and severe rheumatic and neurological sequelae, whereas dengue disease is potentially fatal. Thus, accurate diagnosis is critical. Objective: To compare presumptive diagnoses based on clinical findings with the differential diagnoses based on specific laboratory tests for each virus. Materials and methods: We performed specific virological and serological tests for both dengue and Chikungunya infections on eight acute-phase blood samples collected from pediatric patients with febrile syndrome. We used RT-PCR to detect dengue and Chikungunya virus, and IgM-capture ELISA to confirm infection by dengue virus. Results: Based on clinical findings, two patients were diagnosed as probable cases of dengue or Chikungunya, and two were diagnosed as probable cases of chikungunya. Four had no presumptive diagnosis of viral infection. Laboratory tests confirmed dengue infection in two patients, Chikungunya infection in two patients, and co-infection by the two viruses in the other four patients. Conclusion: Clinical findings were not sufficient to make a diagnosis in pediatric patients with febrile syndrome; specific laboratory tests were required to establish the etiologic agent of the disease.Introducción. Las infecciones por el virus del dengue y del chikungunya presentan síntomas clínicos similares, lo cual dificulta el diagnóstico clínico. Además, son transmitidas por los mismos vectores, por lo que en una región puede haber circulación e infección simultánea con los dos virus. Los resultados de cada enfermedad, no obstante, son diferentes: la fiebre del chikungunya rara vez es fatal, pero puede dejar secuelas de tipo articular y neurológico, en tanto que el dengue es potencialmente fatal. De ahí la importancia de un diagnóstico preciso y oportuno.Objetivo. Comparar el diagnóstico presuntivo basado en los hallazgos clínicos con el diagnóstico diferencial hecho mediante pruebas de laboratorio.Materiales y métodos. Se utilizaron pruebas virológicas y serológicas específicas para dengue y chikungunya en ocho muestras de sangre de pacientes pediátricos con síndrome febril. Se empleó la reacción en cadena de la polimerasa con transcriptasa inversa para detectar los virus del dengue y del chikungunya y el método de ELISA basado en la captura de IgM para confirmar los casos de dengue.Resultados. Con base en los hallazgos clínicos, dos pacientes se clasificaron como casos probables de dengue o chikungunya, dos como casos probables de chikungunya y en cuatro no hubo diagnóstico presuntivo de infección viral. Las pruebas de laboratorio confirmaron la infección por el virus del dengue en dos pacientes, por el virus del chikungunya en otros dos e infección simultánea de dengue y chikungunya en los cuatro restantes.Conclusión. Los hallazgos clínicos no fueron suficientes para hacer un diagnóstico en pacientes pediátricos con síndrome febril, por lo cual se requirieron pruebas específicas de laboratorio para establecer con precisión el agente etiológico causante de la enfermedad.

Clinical utility of urinary gluten immunogenic peptides in the follow-up of patients with coeliac disease

[Background] Gluten-free diet (GFD) is the only treatment for patients with coeliac disease (CD) and its compliance should be monitored to avoid cumulative damage.[Aims] To analyse gluten exposures of coeliac patients on GFD for at least 24 months using different monitoring tools and its impact on duodenal histology at 12-month follow-up and evaluate the interval of determination of urinary gluten immunogenic peptides (u-GIP) for the monitoring of GFD adherence.[Methods] Ninety-four patients with CD on a GFD for at least 24 months were prospectively included. Symptoms, serology, CDAT questionnaire, and u-GIP (three samples/visit) were analysed at inclusion, 3, 6, and 12 months. Duodenal biopsy was performed at inclusion and 12 months.[Results] At inclusion, 25.8% presented duodenal mucosal damage; at 12 months, this percentage reduced by half. This histological improvement was indicated by a reduction in u-GIP but did not correlate with the remaining tools. The determination of u-GIP detected a higher number of transgressions than serology, regardless of histological evolution type. The presence of >4 u-GIP-positive samples out of 12 collected during 12 months predicted histological lesion with a specificity of 93%. Most patients (94%) with negative u-GIP in ≥2 follow-up visits showed the absence of histological lesions (p < 0.05).[Conclusion] This study suggests that the frequency of recurrent gluten exposures, according to serial determination of u-GIP, could be related to the persistence of villous atrophy and that a more regular follow-up every 6 months, instead of annually, provides more useful data about the adequate adherence to GFD and mucosal healing.This study was funded in part by Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía (PI-0427-2017 and PI-0053-2018).Peer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (II). Innovación docente en Filosofía

El PIMCD "Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (II). Innovación docente en Filosofía" se ocupa de conceptos generalmente eludidos por la tradición teórica (contando como núcleos aglutinantes los de la precariedad laboral, la exclusión social y diversidad funcional o discapacidad), cuyo análisis propicia nuevas prácticas en la enseñanza universitaria de filosofía, adoptando como meta principal el aprendizaje centrado en el estudiantado, el diseño de nuevas herramientas de enseñanza y el fomento de una universidad inclusiva. El proyecto cuenta con 26 docentes de la UCM y otros 28 docentes de otras 17 universidades españolas (UV, UNED, UGR, UNIZAR, UAH, UC3M, UCA, UNIOVI, ULL, EHU/UPV, UA, UAM, Deusto, IFS/CSIC, UCJC, URJC y Univ. Pontificia de Comillas), que permitirán dotar a las actividades programadas de un alcance idóneo para consolidar la adquisición de competencias argumentativas y dialécticas por parte de lxs estudiantes implicados en el marco de los seminarios previstos. Se integrarán en el PIMCD, aparte de PDI, al menos 26 estudiantes de máster y doctorado de la Facultad de Filosofía, a lxs que acompañarán durante el desarrollo del PIMCD 4 Alumni de la Facultad de Filosofía de la UCM, actualmente investigadores post-doc y profesorxs de IES, cuya experiencia será beneficiosa para su introducción en la investigación. Asimismo, el equipo cuenta con el apoyo de varixs profesorxs asociadxs, que en algunos casos son también profesores de IES. Varixs docentes externos a la UCM participantes en el PIMCD poseen una dilatada experiencia en la coordinación de proyectos de innovación de otras universidades, lo que redundará en beneficio de las actividades a desarrollar. La coordinadora y otrxs miembros del PIMCD pertenecen a la Red de Innovación Docente en Filosofia (RIEF), puesta en marcha desde la Universitat de València (http://rief.blogs.uv.es/encuentros-de-la-rief/), a la que mantendremos informada de las actividades realizadas en el proyecto. Asimismo, lxs 6 miembros del PAS permitirán difundir debidamente las actividades realizadas en el PIMCD entre lxs estudiantes Erasmus IN del curso 2019/20 en la Facultad de Filosofía, de la misma manera que orientar en las tareas de maquetación y edición que puedan ser necesarias de cara a la publicación de lxs resultados del PIMCD y en las tareas de pesquisa bibliográfica necesarias para el desarrollo de los objetivos propuestos. Han manifestado su interés en los resultados derivados del PIMCD editoriales especializadas en la difusión de investigaciones predoctorales como Ápeiron y CTK E-Books

Dengue disease diagnosis: A puzzle to be solved

Dengue is an infection caused by dengue virus and is the most important arthropod transmitted viral disease in the world, causing near 100 million cases and 50 000 fatalities each year. Health authorities believe that these numbers will grow in coming years. In Colombia, almost 600 municipalities are in regions with Aedes aegypti circulation, and the presence of four dengue serotypes has been demonstrated. Despite the increasing knowledge about disease pathogenesis and the dengue virus, some technical or scientific difficulties with diagnosing dengue remain, negatively affecting both public health surveillance and the appropriate attention to patients in health settings and hospitals. This paper reviews the principles and developments of the current diagnostic techniques for dengue, pointing out the difficulties with making accurate dengue diagnoses and case confirmations in public health and specialized laboratories. The principles and limitations of MAC-ELISA, IgG serology, viral NS1 detection and viral isolation by cell culture are presented. In addition, the review of immunochromatography techniques (rapid diagnostic tests) that have been put forward to help the point-of-care diagnosis is proposed. This paper is intended to bring forward some points of view about the issues related to dengue diagnosis and contribute to improve the discussion surrounding the strategies and techniques needed for reducing the impact of the disease and favoring its control

Endothelial Dysfunction, HMGB1, and Dengue: An Enigma to Solve

Dengue is a viral infection caused by dengue virus (DENV), which has a significant impact on public health worldwide. Although most infections are asymptomatic, a series of severe clinical manifestations such as hemorrhage and plasma leakage can occur during the severe presentation of the disease. This suggests that the virus or host immune response may affect the protective function of endothelial barriers, ultimately being considered the most relevant event in severe and fatal dengue pathogenesis. The mechanisms that induce these alterations are diverse. It has been suggested that the high mobility group box 1 protein (HMGB1) may be involved in endothelial dysfunction. This non-histone nuclear protein has different immunomodulatory activities and belongs to the alarmin group. High concentrations of HMGB1 have been detected in patients with several infectious diseases, including dengue, and it could be considered as a biomarker for the early diagnosis of dengue and a predictor of complications of the disease. This review summarizes the main features of dengue infection and describes the known causes associated with endothelial dysfunction, highlighting the involvement and possible relationship between HMGB1 and DENV