Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

BACKGROUND: Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. METHODS: A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. RESULTS: Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6-24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7-22.7 pg/mL; p1, even after adjustment.CONCLUSIONS: The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT01335087

Starting a family in another land : spaniards in Malta, 1580s to 1640s

Demographers are confronted with considerable difficulties when they set about studying family structures. This paper will seek to show that the behaviour of Spanish migrants in Malta in the early modern period conforms to the migratory patterns evident elsewhere. The term ‘migrant’ is here understood as referring to a person who changes his habitual place of residence in a more or less permanent form by crossing an administrative boundary. A key marker of a permanent move to a new land is marriage and the starting of a family there.peer-reviewe

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control. Methods: Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC, n=8), at two and one year before the loss of control, were comparedwith a control group of ECwho persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n=8). The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polyfunctionality of HIV-specific CD8+T-cell response. Findings: Our data suggest that, before the loss of control, TCs showed a specific circulating metabolomic profile characterized by aerobic glycolytic metabolism, deregulated mitochondrial function, oxidative stress and increased immunological activation. In addition, CD8+ T-cell polyfunctionality was strongly associated with metabolite levels. Finally, valine was the main differentiating factor between TCs and PCs. Interpretation: All these metabolomic differences should be considered not only as potential biomarkers but also as therapeutic targets in HIV infection.Instituto Carlos III PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186 INT11/240 INT12/282 INT15/226Fondos Europeos para el Desarrollo Regional PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186FEDER PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186FEDER PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186Programa de Suport als Grups de Recerca 2017SGR948 2014SGR250Gilead Fellowship Program GLD14/293 GLD17/00299Red de Investigación en Sida RD12/0017/0005 RD16/0025/0006 RD12/0017/0029 RD16/0025/0020Junta de Andalucía C-0032/17Generalitat de Catalunya PERIS SLT002/16/0010

The prognostic value of catastrophizing for predicting the clinical evolution of low back pain patients: a study in routine clinical practice within the Spanish National Health Service

Francisco Javier Cano García es miembro de la Spanish Back Pain Research Network (Red Española de Investigadores en Dolencias de la Espalda (REIDE) y coautor del artículoBackground context Experimental studies suggest that catastrophizing may worsen the prognosis of low back pain (LBP) and LBP-related disability and increase the risk of chronicity. Purpose To assess the prognostic value of baseline catastrophizing for predicting the clinical evolution of LBP patients in routine clinical practice and the association between the evolution of pain and catastrophizing. Study design/setting Prospective study in routine clinical practice of the Spanish National Health Service. Patient sample One thousand four hundred twenty-two acute and chronic adult LBP patients treated in primary and hospital care. Outcome measures Pain, disability, and catastrophizing measured through validated instruments. Methods Patients were managed according to routine clinical practice. Outcome measures were assessed at baseline and 3 months later. Logistic regression models were developed to estimate the association between baseline catastrophizing score and the improvement of LBP and disability, adjusting for baseline LBP and leg pain (LP) severity, disability, duration of the pain episode, workers' compensation coverage, radiological findings, failed back surgery, and diagnostic procedures and treatments undertaken throughout the study. Another model was developed to estimate the association between the evolution of LBP and the change in catastrophizing, adjusting for the same possible confounders plus the evolution of LP and disability. Models were repeated excluding the treatments undergone after the baseline assessment. Results Regression models showed that the degree of baseline catastrophizing does not predict the evolution of LBP and disability. Conversely, as the degree of pain improvement increases, so does the odds ratio for improvement in catastrophizing, ranging from three (95% confidence interval [95% CI], 2.00–4.50; p<.001) for improvements in pain between 1.1 and 4 visual analog scale (VAS) points, to 7.3 (95% CI, 3.49–15.36; p<.001) for improvements in pain more than 6.1 VAS points. Similar results were obtained when treatments were excluded from the models. Conclusions In routine practice, assessing the baseline score for catastrophizing does not help clinicians to predict the evolution of LBP and disability at 3 months.Spanish Ministry of Health’s Agency for QualityKovacs Foundatio

Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined

Multiple Sporadic Colorectal Cancers Display a Unique Methylation Phenotype

The members of the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association are: Hospital 12 de Octubre, Madrid: Juan Diego Morillas (local coordinator), Raquel Muñoz, Marisa Manzano, Francisco Colina, Jose Díaz, Carolina Ibarrola, Guadalupe López, Alberto Ibáñez; Hospital Clínic, Barcelona: Antoni Castells (local coordinator), Virgínia Piñol, Sergi Castellví-Bel, Francesc Balaguer, Victoria Gonzalo, Teresa Ocaña, María Dolores Giráldez, Maria Pellisé, Anna Serradesanferm, Leticia Moreira, Miriam Cuatrecasas, Josep M. Piqué; Hospital Clínico Universitario, Zaragoza: Ángel Lanas (local coordinator), Javier Alcedo, Javier Ortego; Hospital Cristal-Piñor, Complexo Hospitalario de Ourense: Joaquin Cubiella (local coordinator), Ma Soledad Díez, Mercedes Salgado, Eloy Sánchez, Mariano Vega; Hospital del Mar, Barcelona: Montserrat Andreu (local coordinator), Anna Abuli, Xavier Bessa, Mar Iglesias, Agustín Seoane, Felipe Bory, Gemma Navarro, Beatriz Bellosillo, Josep Ma Dedeu, Cristina Álvarez, Begoña Gonzalez; Hospital San Eloy, Baracaldo and Hospital Donostia, CIBERehd, University of Country Basque, San Sebastián: Luis Bujanda (local coordinator) Ángel Cosme, Inés Gil, Mikel Larzabal, Carlos Placer, María del Mar Ramírez, Elisabeth Hijona, Jose M. Enríquez-Navascués, Jose L. Elosegui; Hospital General Universitario de Alicante: Artemio Payá (EPICOLON I local coordinator), Rodrigo Jover (EPICOLON II local coordinator), Cristina Alenda, Laura Sempere, Nuria Acame, Estefanía Rojas, Lucía Pérez-Carbonell; Hospital General de Granollers: Joaquim Rigau (local coordinator), Ángel Serrano, Anna Giménez; Hospital General de Vic: Joan Saló (local coordinator), Eduard Batiste-Alentorn, Josefina Autonell, Ramon Barniol; Hospital General Universitario de Guadalajara and Fundación para la Formación e Investigación Sanitarias Murcia: Ana María García (local coordinator), Fernando Carballo, Antonio Bienvenido, Eduardo Sanz, Fernando González, Jaime Sánchez, Akiko Ono; Hospital General Universitario de Valencia: Mercedes Latorre (local coordinator), Enrique Medina, Jaime Cuquerella, Pilar Canelles, Miguel Martorell, José Ángel García, Francisco Quiles, Elisa Orti; CHUVI-Hospital Meixoeiro, Vigo: EPICOLON I: Juan Clofent (local coordinator), Jaime Seoane, Antoni Tardío, Eugenia Sanchez; EPICOLON II: Ma Luisa de Castro (local coordinator), Antoni Tardío, Juan Clofent, Vicent Hernández; Hospital Universitari Germans Trias i Pujol, Badalona and Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL: Xavier Llor (local coordinator), Rosa M. Xicola, Marta Piñol, Mercè Rosinach, Anna Roca, Elisenda Pons, José M. Hernández, Miquel A. Gassull; Hospital Universitari Mútua de Terrassa: Fernando Fernández-Bañares (local coordinator), Josep M. Viver, Antonio Salas, Jorge Espinós, Montserrat Forné, Maria Esteve; Hospital Universitari Arnau de Vilanova, Lleida: Josep M. Reñé (local coordinator), Carmen Piñol, Juan Buenestado, Joan Viñas; Hospital Universitario de Canarias: Enrique Quintero (local coordinator), David Nicolás, Adolfo Parra, Antonio Martín; Hospital Universitario La Fe, Valencia: Lidia Argüello (local coordinator), Vicente Pons, Virginia Pertejo, Teresa Sala; Hospital Sant Pau, Barcelona: Dolors Gonzalez (local coordinator), Eva Roman, Teresa Ramon, Maria Poca, Ma Mar Concepción, Marta Martin, Lourdes Pétriz; Hospital Xeral Cies, Vigo: Daniel Martinez (local coordinator); Fundacion Publica Galega de Medicina Xenomica (FPGMX), CIBERER, Genomic Medicine Group-University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain: Ángel Carracedo (local coordinator), Clara Ruiz-Ponte, Ceres Fernández-Rozadilla, Ma Magdalena Castro; Hospital Universitario Central de Asturias: Sabino Riestra (local coordinator), Luis Rodrigo; Hospital de Galdácano, Vizcaya: Javier Fernández (local coordinator), Jose Luis Cabriada; Fundación Hospital de Calahorra (La Rioja) La Rioja: Luis Carreño (local coordinator), Susana Oquiñena, Federico Bolado; Hospital Royo Villanova, Zaragoza: Elena Peña (local coordinator), José Manuel Blas, Gloria Ceña, Juan José Sebastián; Hospital Universitario Reina Sofía, Córdoba: Antonio Naranjo (local coordinator).Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.This work was supported by grants from the Hospital Clínic of Barcelona (Josep Font grant), Ministerio de Economí­a y Competitividad (SAF 2007-64873 and SAF2010-19273), Fundación Científica de la Asociación Española contra el Cáncer, and Instituto de Salud Carlos III (PI10/00384). “Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER). Unión Europea. Una manera de hacer Europa”. CIBEREHD is funded by the Instituto de Salud Carlos III

Reanalyzing language expectations: Native language knowledge modulates the sensitivity to intervening cues during anticipatory processing

Issue Online:21 September 2018We investigated how native language experience shapes anticipatory language processing. Two groups of bilinguals (either Spanish or Basque natives) performed a word matching task (WordMT) and a picture matching task (PictureMT). They indicated whether the stimuli they visually perceived matched with the noun they heard. Spanish noun endings were either diagnostic of the gender (transparent) or ambiguous (opaque). ERPs were time-locked to an intervening gender-marked determiner preceding the predicted noun. The determiner always gender agreed with the following noun but could also introduce a mismatching noun, so that it was not fully task diagnostic. Evoked brain activity time-locked to the determiner was considered as reflecting updating/reanalysis of the task-relevant preactivated representation. We focused on the timing of this effect by estimating the comparison between a gender-congruent and a gender-incongruent determiner. In the WordMT, both groups showed a late N400 effect. Crucially, only Basque natives displayed an earlier P200 effect for determiners preceding transparent nouns. In the PictureMT, both groups showed an early P200 effect for determiners preceding opaque nouns. The determiners of transparent nouns triggered a negative effect at similar to 430 ms in Spanish natives, but at similar to 550 ms in Basque natives. This pattern of results supports a "retracing hypothesis" according to which the neurocognitive system navigates through the intermediate (sublexical and lexical) linguistic representations available from previous processing to evaluate the need of an update in the linguistic expectation concerning a target lexical item.Spanish Ministry of Economy and Competitiveness (MINECO), Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER) (grant PSI2015‐65694‐P to N. M.), Spanish Ministry of Economy and Competitiveness “Severo Ochoa” Programme for Centres/Units of Excellence in R&D (grant SEV‐2015‐490