The Potential of Circulating Cell-Free DNA Methylation as an Epilepsy Biomarker

This article is part of the Research Topic: Cellular and Molecular Targets In Epileptogenesis Focusing on Disease Prevention.Circulating cell-free DNA (cfDNA) are highly degraded DNA fragments shed into the bloodstream. Apoptosis is likely to be the main source of cfDNA due to the matching sizes of cfDNA and apoptotic DNA cleavage fragments. The study of cfDNA in liquid biopsies has served clinical research greatly. Genetic analysis of these circulating fragments has been used in non-invasive prenatal testing, detection of graft rejection in organ transplants, and cancer detection and monitoring. cfDNA sequencing is, however, of limited value in settings in which genetic association is not well-established, such as most neurodegenerative diseases.Recent studies have taken advantage of the cell-type specificity of DNA methylation to determine the tissue of origin, thus detecting ongoing cell death taking place in specific body compartments. Such an approach is yet to be developed in the context of epilepsy research. In this article, we review the different approaches that have been used to monitor cell-type specific death through DNA methylation analysis, and recent data detecting neuronal death in neuropathological settings. We focus on the potential relevance of these tools in focal epilepsies, like Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), characterized by severe neuronal loss. We speculate on the potential relevance of cfDNA methylation screening for the detection of neuronal cell death in individuals with high risk of epileptogenesis that would benefit from early diagnosis and consequent early treatment.RM-F was funded by an FCT (Fundação para a Ciência e Tecnologia) fellowship (grant number SFRH/BD/137900/2018). Unit for Multidisciplinary Research in Biomedicine (UMIB) was funded by FCT Portugal (grant numbers UIDB/00215/2020 and UIDP/00215/2020), and Laboratory for Integrative and Translational Research in Population Health (ITR) (LA/P/0064/2020).info:eu-repo/semantics/publishedVersio

The Potential of Circulating Cell-Free DNA Methylation as an Epilepsy Biomarker

Circulating cell-free DNA (cfDNA) are highly degraded DNA fragments shed into the bloodstream. Apoptosis is likely to be the main source of cfDNA due to the matching sizes of cfDNA and apoptotic DNA cleavage fragments. The study of cfDNA in liquid biopsies has served clinical research greatly. Genetic analysis of these circulating fragments has been used in non-invasive prenatal testing, detection of graft rejection in organ transplants, and cancer detection and monitoring. cfDNA sequencing is, however, of limited value in settings in which genetic association is not well-established, such as most neurodegenerative diseases.Recent studies have taken advantage of the cell-type specificity of DNA methylation to determine the tissue of origin, thus detecting ongoing cell death taking place in specific body compartments. Such an approach is yet to be developed in the context of epilepsy research. In this article, we review the different approaches that have been used to monitor cell-type specific death through DNA methylation analysis, and recent data detecting neuronal death in neuropathological settings. We focus on the potential relevance of these tools in focal epilepsies, like Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), characterized by severe neuronal loss. We speculate on the potential relevance of cfDNA methylation screening for the detection of neuronal cell death in individuals with high risk of epileptogenesis that would benefit from early diagnosis and consequent early treatment

Quality of life of patients with diabetes mellitus types 1 and 2 from a regerral health care center in Minas Gerais, Brazil

Quality of life (QoL) characteristics are important in patients with diabetes mellitus (DM 1 and 2). Aim: Evaluate QoL and DM-associated factors among diabetic patients. Methods: Patients attending a University Hospital interviewed about sociodemographic, clinical and QoL characteristics, with QoL measured via the EQ-5D. Descriptive analysis, correlation, linear regression, univariate and multivariate analysis were performed. Results: 346 patients took part, comprising 67% women, 59% with DM2, and 32% DM1. DM 1 patients had a mean QoL of 0.7369, with retinopathy, depression, dyslipidemia and a serious hypoglycemic crisis significantly reducing QoL. Patients with DM type 2 had mean QoL 0.6582, with hypertension, neuropathy, depression, cancer and dyslipidemia significantly reducing QoL. Reduced QoL also correlated with a lack of physical exercise. Males with both DM1 and 2 had a better QoL. Conclusion: Need for better disease monitoring and control combined with effective activities to improve self-care, reduce complications and improve patients’ QoL

Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22

Objective: ATP-gated ionotropic P2X7 receptors (P2X7R) actively participate in epilepsy and other neurological disorders. Neocortical nerve terminals of patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) express higher P2X7R amounts. Overexpression of P2X7R bolsters ATP signals during seizures resulting in glial cell activation, cytokines production, and GABAergic rundown with unrestrained glutamatergic excitation. In a mouse model of status epilepticus, increased expression of P2X7R has been associated with the down-modulation of the non-coding micro RNA, miR-22. MiR levels are stable in biological fluids and normally reflect remote tissue production making them ideal disease biomarkers. Here, we compared P2X7R and miR-22 expression in epileptic brains and in the serum of patients with MTLE-HS, respectively. Methods: Quantitative RT-PCR was used to evaluate the expression of P2X7R in the hippocampus and anterior temporal lobe of 23 patients with MTLE-HS and 10 cadaveric controls. Confocal microscopy and Western blot analysis were performed to assess P2X7R protein amounts. MiR-22 expression was evaluated in cell-free sera of 40 MTLE-HS patients and 48 healthy controls. Results: Nerve terminals of the hippocampus and neocortical temporal lobe of MTLE-HS patients overexpress (p 3) anti-epileptic drug (AED) regimens. Conclusion: Data show that there is an inverse relationship between miR-22 serum levels and P2X7R expression in the hippocampus and neocortex of MTLE-HS patients, which implies that measuring serum miR-22 may be a clinical surrogate of P2X7R brain expression in the MTLE-HS. Moreover, the high area under the ROC curve (0.777; 95% CI 0.629-0.925; p = 0.001) suggests that low miR-22 serum levels may be a sensitive predictor of poor response to AEDs among MTLE-HS patients. Results also anticipate that targeting the miR-22/P2X7R axis may be a good strategy to develop newer AEDs.This research was partial funded by a BICE Tecnifar Grant. The work performed in PC-S’s Lab was partially supported by UP/Santander Totta and Fundação para a Ciência e Tecnologia (FCT, POCTI PTDC/SAU-PUB/28311/2017—EPIRaft grant and Fundo Europeu de Desenvolvimento Regional—FEDER funding and COMPETE—MedInUP projects Pest-OE/SAU/UI215/2014, UID/BIM/4308/2016, UIDB/04308/2020 and UIDP/04308/2020). Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT) Portugal (grant numbers UIDB/00215/2020 and UIDP/00215/2020) and ITR—Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020). RM-F was in receipt of an FCT PhD studentship (SFRH/BD/137900/2018).info:eu-repo/semantics/publishedVersio

Association between Elevated Iodine Intake and IQ among School Children in Portugal

Funding Information: This project was funded through grants by the Public Health Initiatives Programme (PT06), financed by EEA Grants Financial Mechanism 2009–2014, and supported by FEDER through the operation POCI-01-0145-FEDER-007746 funded by the Programa Operacional Competitividade e Internacionalização—COMPETE2020 and by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference UIDP/4255/2020) and within the scope of the project RISE, Associated Laboratory (reference LA/P/0053/2020). DP and VCF also received individual funding from Fundação para a Ciência e a Tecnologia (SFRH/BPD/109158/2015 in the first case; SFRH/BPD/109153/2015, UIDB/50006/2020, UIDP/50006/2020, and LA/P/0008/2020 in the second case).The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven’s Colored Progressive Matrices) were dichotomized to <50 (“below-average” IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food’s tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO’s criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11–2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.publishersversionpublishe

Encoprese e intervenção psicológica: revisão de literatura

Studies have shown that encopresis, related to bowel control disorder, can bring significant impact for the individual life, such as low self-esteem and deficits in social interaction. Despite the significant impairment recognized that this disorder can have on child development, the scientific literature has given little attention to the theme, with a low number of publications on the subject. Thus, this paper investigated Brazilian publications in psychology related to encopresis between 1994 and 2013 in data base Lilacs and Scielo. 231 articles were found and were selected those that reported only intervention in encopresis. There were five articles and four published by the same journal and described behavioral interventions, and one author wrote three. The other one was psychoanalytic. The surveys were conducted with children and adolescents and behavioral interventions have been successful with remission of encopresis symptoms. The data affirm the deficiency in publications in the area and possibly limited number of psychologists investigating the issue, which is of significant importance.Los estudios han demostrado que la encopresis, relacionado con el trastorno intestinal control, pueden aportar importantes para la vida del individuo, tales como la baja autoestima y déficit en los efectos de interacción social. A pesar del deterioro significativo reconocido que este trastorno puede tener en el desarrollo del niño, la literatura científica ha prestado poca atención al tema, con un bajo número de publicaciones sobre el sujeto. Por lo tanto, este trabajo investiga las publicaciones brasileñas en psicología relacionada con encopresis entre los años 1994 y 2013 en las basis Lilacs e Scielo. Se encontraron 231 artículos e seleccionaron solamente artículos que informaron la intervención in encopresis. Se encontraron cinco artículos, y cuatro en la misma revista con intervenciones conductuales, siendo tres de lo mismo autor. Lo quinto articulo era de la psicoanálisis. Las encuestas se llevaron a cabo con las personas y las intervenciones conductuales han tenido éxito con la remisión de los síntomas encopréticos. Los datos confirman la deficiencia en las publicaciones de la zona y posiblemente limitado número de psicólogos que investiga el asunto, que es de gran importancia.Estudos têm demonstrado que a encoprese, transtorno relacionado ao controle esfincteriano, pode trazer impactos significativos para a vida do indivíduo, tais como baixa autoestima e déficit em interação social. Apesar de reconhecido o importante comprometimento que tal transtorno pode causar no desenvolvimento infantil, a literatura científica tem dado pouca importância ao tema, apresentando um baixo número de publicações sobre o assunto. Dessa forma, este artigo investigou as publicações nacionais em psicologia relacionadas à encoprese entre os anos de 1994 a 2013 nas bases de dados Lilacs e Scielo. Foram encontrados 231 artigos em toda a publicação para este assunto e período, e selecionados cinco para a análise, sendo aqueles que relatavam intervenção em encoprese. Desses artigos, quatro foram publicados na mesma revista e descreveram intervenções comportamentais, sendo três do mesmo autor. O quinto artigo era da abordagem psicanalítica. As pesquisas foram realizadas com crianças e adolescentes e as intervenções comportamentais tiveram êxito com remissão dos sintomas encopréticos. Os dados afirmam a deficiência em publicações na área e número restrito de pesquisadores investigando o tema, que é de relevância significativa

La integración latinoamericana en debate : incertidumbre, formatos institucionales fragmentados y caminos alternativos latentes

Este libro retoma la temática de la integración desde una mirada sociológica para comprender, en diálogo con otras perspectivas de las ciencias sociales, las trayectorias y experiencias propias ensayadas en América Latina. Así pues, se presentan las modalidades de regionalismo poshegemónico o posneoliberal con los diversos formatos y contenidos ensayados en las iniciativas de integración en la región, y los distintos actores políticos y sociales emergentes en los diversos escenarios y escalas de los procesos de integración, y se abordan las múltiples dimensiones involucradas en los procesos de integración más allá de los aspectos exclusivamente comerciales, así como las dinámicas de las desigualdades y las disputas internas en los juegos de poder geopolítico y de actores sociales