Relation of prenatal and postnatal PM_2.5 exposure with cognitive and motor function among preschool-aged children

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative β (βcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1–9 (βcum = −2.55, 95%CrI = −3.53,-1.56) and on gross motor scores in weeks 7–17 (βcum = −2.27,95%CrI = −3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (βcum = −0.17, 95%CrI = −0.26,-0.09). In the postnatal period (from age 0.5–1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (β = −2.42, 95%CrI = −3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.</p

Relation of prenatal and postnatal PM_2.5 exposure with cognitive and motor function among preschool-aged children

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m3 increase in PM2.5 and aggregated across adjacent statistically significant lags using cumulative β (βcum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM2.5 with fetal growth and child sex. We did not observe associations of PM2.5 exposure with lower GCI scores. We found a period of susceptibility to PM2.5 on fine motor scores in gestational weeks 1–9 (βcum = −2.55, 95%CrI = −3.53,-1.56) and on gross motor scores in weeks 7–17 (βcum = −2.27,95%CrI = −3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (βcum = −0.17, 95%CrI = −0.26,-0.09). In the postnatal period (from age 0.5–1.2 years), we observed a window of susceptibility to PM2.5 on lower perceptual-performance (β = −2.42, 95%CrI = −3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM2.5 for children's perceptual-performance.</p

Residential green and blue spaces and working memory in children aged 6–12 years old. Results from the INMA cohort

Availability of green and blue spaces in the area of residence has been related to various health outcomes during childhood, including neurodevelopment. Some studies have shown that children living in greener and/or bluer areas score better on cognitive tasks although the evidence is inconsistent. These protective effects are hypothesized to occur in part through reductions in air pollution exposure and odds of attention-deficit/hyperactivity disorder (ADHD). This study analysed the effects of residential green and blue spaces on working memory of children in the Spanish INfancia y Medio Ambiente (INMA) birth cohort and the potential joint mediating role of air pollution and ADHD. The study samples were composed of 1738 six-to eight-year-olds (M = 7.53, SD = 0.68, 49% female) and 1449 ten-to twelve-year-olds (M = 11.18, SD = 0.69, 50% female) living in Asturias, Gipuzkoa, Sabadell or Valencia, Spain. Individual Normalized Difference Vegetation Index (NDVI) values in 100-, 300- and 500-m buffers and availability of green and blue spaces &gt;5000 m2 in 300-m buffers were calculated using Geographic Information Systems software. Individual NO2 values for the home environment were estimated using ESCAPE's land use regression models. ADHD diagnosis was reported by participants' parents via a questionnaire. Working memory was measured with numbers and colours (in the younger group only) N-back tests (2- and 3-back d’). Mixed-effects models informed of the beneficial effects of NDVI in a 300-m buffer on numerical working memory in the younger sample although the results were not consistent for all d’ scores considered and failed to detect significant effects through the candidate mediators. Availability of major blue spaces did not predict working memory performance. Provision of green spaces may play a role in children's working memory but further research is required.</p

Social inequalities, green and blue spaces and mental health in 6–12 years old children participating in the INMA cohort

Availability of green and blue spaces in the area of residence has been related to various health outcomes during childhood, including mental health. These environmental exposures are not evenly distributed among socioeconomic groups, which may increase social inequalities in mental health. The mechanisms through which natural environments may promote mental health are numerous and diverse. This study aimed to explore 1) the potential associations of socioeconomic variables (SES and maternal education attainment) with mental health scores and residential greenness, blueness and NO2 metrics, and, 2) the association between greenness and blueness metrics and mental health scores of children in the Spanish INfancia y Medio Ambiente (INMA) birth cohort at two different time points. The study samples were composed of 1738 six-to eight-year-olds (49% female) and 1449 ten-to twelve-year-olds (living in Asturias, Gipuzkoa, Sabadell and Valencia, Spain. Individual Normalized Difference Vegetation Index (NDVI) values in 100-, 300- and 500-m buffers and availability of green and blue spaces &gt;5000 m2 in 300-m buffers were calculated using Geographic Information Systems software. Residential NO2 values were estimated using land use regression models. Internalizing, externalizing and total problems scores were obtained with the Strengths and Difficulties Questionnaire (SDQ). Linear and logistic mixed-effects models revealed unequal distribution of environmental exposures by SES and maternal education but did not show statistically significant associations between greenness and blueness metrics and mental health indicators. The protective effect of green and blue spaces on children's mental health could not be confirmed in this study and therefore further research is required.</p

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages

Genomic determinants associated with SARS-CoV-2 virulence

Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021.This work was funded by the Instituto de Salud Carlos III project COV2o/oo140 and COV2o/ o0437,Spanish National Research Council project CSIC­ COV19·0l1 and CSIC-COVID19-082,and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI).Action co-financed by the European Union through the Operatianal Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020.MC is supported by Ramón y Cajal program from Ministerio de Ciencia,grant RTI2018-094399-A-I00.Peer reviewe

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig CardellsThe coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.Peer reviewe

Prognostic role of host cyclooxygenase and cytokine genotypes in a caucasian cohort of patients with gastric adenocarcinoma

Background: Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC. Methodology: Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays. Clinical and histological information was collected prospectively. Survival curves were estimated by the Kaplan-Meier method and compared using the log rank test. Outcome was determined by analysis of Cox proportional hazards, adjusting for confounding factors. Results: The median follow-up period and median overall survival (OS) time were 9.9 months (range 0.4-120.3) and 10.9 months (95% CI: 8.9-14.1), respectively. Multivariate analysis identified tumor stages III (HR, 3.23; 95% CI:2-5.22) and IV (HR, 5.5; 95% CI: 3.51-8.63) as independent factors associated with a significantly reduced OS, whereas surgical treatment (HR: 0.44; 95%CI: 0.3-0.6) was related to a better prognosis of the disease. Concerning genetic factors, none of the 23 polymorphisms evaluated in the current study did influence survival. Moreover, no gene-environment interactions on GAC prognosis were observed. Conclusions: Our results show that, in our population, the panel of selected pro- and anti-inflammatory cytokine, and cyclooxygenase gene polymorphisms are not relevant in determining the prognosis of gastric adenocarcinoma. © 2012 García-González et al.This study was supported by the Spanish >Fondo de Investigaciones Sanitarias> (grants PI05/0405 and PS09/00213), and Instituto de Salud Carlos III (CIBER de enfermedades hepaticas y digestivas).Peer Reviewe

Cucumber Mosaic Virus 2b Protein Subcellular Targets and Interactions: Their Significance to RNA Silencing Suppressor Activity

10 páginas, 8 figuras -- PAGS nros. 294-303The RNA silencing suppressor activity of the 2b protein of Cucumber mosaic virus (CMV) has been variously attributed to its nuclear targeting, its interaction with and inhibition of Argonaute 1 (AGO1), or its ability to bind small RNAs in vitro. In addition, the 2b ortholog of Tomato aspermy virus forms aggregates and binds RNAs in vitro. We have further studied the relationships between CMV 2b protein silencing suppressor activity and its subcellular distribution, protein-protein interactions in vivo, and interactions with small interfering RNAs in vitro. To do this, we tagged the protein with fluorescent markers and showed that it retained suppressor activity. We showed that the 2b protein is present in the nucleolus and that it self-interacts and interacts with AGO1 and AGO4 in vivo. Using a battery of mutants, we showed that the putative nuclear localization signals and phosphorylation motif of the 2b protein are not required for self-interaction or for interaction with AGO proteins. The occurrence of neither of these interactions or of nucleolar targeting was sufficient to provide local silencing-suppression activity. In contrast, the ability of the 2b protein to bind small RNAs appears to be indispensable for silencing suppressor functionKim for providing the binary construct expressing fibrillarin-mRFP. Work at T. C Canto’s lab was funded by grants 200740I003 from the CSIC, grant L2008-03482 from the Spanish Ministry of Innovation and Science, and bilateral grant P2008RU03 from the Spanish Ministry of Innovation and Science and the Russian Foundation for Basic Research. I. González s recipient of a Ph.D. grant from the Spanish Ministry of Innovation and Science. L. Martínez, C. Llave, and F. Atencio were funded by the Spanish Ministry of Innovation and Science. P. Palukaitis was funded by the Scottish Executive Research Evaluation and Rural Affairs Directorate. M. G. Lewsey and J. P. Carr were funded by Biotechnology and Biological Sciences Research Council grant BB/D008204/1Peer reviewe