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Morales-Rosello J.,Polytechnic University of Valencia | Hervas-Marin D.,Institute Investigacion Sanitaria La Fe | Perales-Marin A.,Polytechnic University of Valencia
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2014

Objective: To determine the existence of Doppler changes in the fetal vertebral, middle cerebral and umbilical arteries prior to term labor. Methods: Five hundred and twenty eight Doppler examinations of the vertebral (VA), middle cerebral (MCA) and umbilical (UA) arteries resistance indices (RI) were performed between 37 and 41 weeks gestation. For each artery, values were converted into multiples of the median (MoM) and were divided into four groups according to the interval to labor and compared using Kruskal-Wallis tests. Subsequently, values were plotted in scattergrams and linear regressions and 95% confidence intervals were calculated. Finally, using multivariate analysis and model averaging, the importance and interrelationship of Doppler measurements in the explanation of the interval to labor was evaluated. Results: Univariate and multivariate analysis confirmed that, independently of gestational age, fetuses examined close to labor presented more intense Doppler changes in the cerebral arteries with a significant reduction of the VA RI and MCA RI. This reduction was larger in the MCA. No significant changes were detected in the UA. Conclusion: Before the onset of term labor, the fetal cerebral flow presents an additional reduction of impedance, which is more intense in the MCA system. © 2014 Informa UK Ltd. All rights reserved. Source

Morales Rosello J.,Polytechnic University of Valencia | Hervas Marin D.,Institute Investigacion Sanitaria La Fe | Perales Marin A.,Polytechnic University of Valencia
Prenatal Diagnosis | Year: 2014

Objective: The objective of this article is to show the clinical utility of the vertebral artery Doppler as an alternative to the middle cerebral artery Doppler in the follow-up of fetuses affected with early-onset growth restriction [fetal growth restriction (FGR)]. Methods: We present a group of fetuses with early-onset FGR in which the vertebral artery resistance index (VA RI) and pulsatility index (VA PI) were measured and plotted along with their references earlier calculated using 1980 Doppler examinations. In addition, the VA and middle cerebral artery (MCA) performance was compared using values converted into multiples of the median. Results: Similar to that of the MCA, VA RI and VA PI percentiles showed curve shapes with higher values at the beginning of the third trimester. The majority of growth-restricted fetuses showed a notorious decrease in the VA impedance, which was not statistically different to that of the MCA. Conclusion: Vertebral artery Doppler values can be obtained throughout the second half of pregnancy. Preliminary data suggest a clinical application in the management of early-onset FGR. © 2013 John Wiley & Sons, Ltd. Source

Morales Rosello J.,Polytechnic University of Valencia | Hervas Marin D.,Institute Investigacion Sanitaria La Fe | Fillol Crespo M.,Servicio de Obstetricia y Ginecologia | Perales Marin A.,Polytechnic University of Valencia
Prenatal Diagnosis | Year: 2012

Objective: To determine the association between Doppler changes in the fetal vertebral (VA), middle cerebral (MCA), and umbilical arteries (UA) and severity of growth restriction (FGR) in fetuses delivered after 34weeks. Method: Five hundred seventy-one Doppler examinations of the VA, MCA, and UA were performed between 26 and 41weeks of gestation. Values were converted into multiples of the median and divided into birth weight (BW) categories: BW>P10th, BW Source

Serrano F.,Institute Investigacion Sanitaria La Fe | Calatayud C.F.,Institute Investigacion Sanitaria La Fe | Blazquez M.,Institute Investigacion Sanitaria La Fe | Torres J.,University of Valencia | And 2 more authors.
Stem Cells | Year: 2013

Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated the role of Gata4 in the reprogramming process and present evidence for a negative role of this family of transcription factors in the induction of pluripotency. Coexpression of Gata4 with Oct4, Klf4, and Sox2 with or without Myc in mouse embryonic fibroblasts greatly impaired reprogramming and endogenous Nanog expression. The lack of Nanog upregulation was associated with a blockade in the transition from the initiation phase of reprogramming to the full pluripotent state characteristic of iPS cells. Addition of Nanog to the reprogramming cocktail blocked the deleterious effects observed with Gata4 expression. Downregulation of endogenous Gata4 by short hairpin RNAs during reprogramming both accelerated and increased the efficiency of the process and augmented the mRNA levels of endogenous Nanog. Using comparative genomics, we identified a consensus binding site for Gata factors in an evolutionary conserved region located 9 kb upstream of the Nanog gene. Using chromatin immunoprecipitation, gel retardation, and luciferase assays, we found that Gata4 bound to this region and inhibited Nanog transcription in mouse embryonic stem cells. Overall, our results describe for first time the negative effect of Gata4 in the reprogramming of somatic cells and highlight the role of Gata factors in the transcriptional networks that control cell lineage choices in the early embryo. © AlphaMed Press. Source

Sabater L.,Institute dinvestigacions Biomediques August Pi i Sunyer IDIBAPS | Gaig C.,Institute dinvestigacions Biomediques August Pi i Sunyer IDIBAPS | Gaig C.,Multidisciplinary Sleep Disorders Unit | Gelpi E.,Institute dinvestigacions Biomediques August Pi i Sunyer IDIBAPS | And 17 more authors.
The Lancet Neurology | Year: 2014

Background: Autoimmunity might be associated with or implicated in sleep and neurodegenerative disorders. We aimed to describe the features of a novel neurological syndrome associated with prominent sleep dysfunction and antibodies to a neuronal antigen. Methods: In this observational study, we used clinical and video polysomnography to identify a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic, University of Barcelona, Spain, for abnormal sleep behaviours and obstructive sleep apnoea. These patients had antibodies against a neuronal surface antigen, which were also present in five additional patients referred to our laboratory for antibody studies. These five patients had been assessed with polysomnography, which was done in our sleep unit in one patient and the recording reviewed in a second patient. Two patients underwent post-mortem brain examination. Immunoprecipitation and mass spectrometry were used to characterise the antigen and develop an assay for antibody testing. Serum or CSF from 298 patients with neurodegenerative, sleep, or autoimmune disorders served as control samples. Findings: All eight patients (five women; median age at disease onset 59 years [range 52-76]) had abnormal sleep movements and behaviours and obstructive sleep apnoea, as confirmed by polysomnography. Six patients had chronic progression with a median duration from symptom onset to death or last visit of 5 years (range 2-12); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid progression with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died 2 months and 6 months, respectively, after symptom onset. In five of five patients, video polysomnography showed features of obstructive sleep apnoea, stridor, and abnormal sleep architecture (undifferentiated non-rapid-eye-movement [non-REM] sleep or poorly structured stage N2, simple movements and finalistic behaviours, normalisation of non-REM sleep by the end of the night, and, in the four patients with REM sleep recorded, REM sleep behaviour disorder). Four of four patients had HLA-DRB1*1001 and HLA-DQB1*0501 alleles. All patients had antibodies (mainly IgG4) against IgLON5, a neuronal cell adhesion molecule. Only one of the 298 controls, who had progressive supranuclear palsy, had IgLON5 antibodies. Neuropathology showed neuronal loss and extensive deposits of hyperphosphorylated tau mainly involving the tegmentum of the brainstem and hypothalamus in the two patients studied. Interpretation: IgLON5 antibodies identify a unique non-REM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy. Funding: Fondo de Investigaciones Sanitarias, Centros de Investigación Biomédica en Red de enfermedades neurodegenerativas (CIBERNED) and Respiratorias (CIBERES), Ministerio de Economía y Competitividad, Fundació la Marató TV3, and the National Institutes of Health. © 2014 Elsevier Ltd. Source

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