Developmental synchrony of thalamocortical circuits in the neonatal brain

10.1016/j.neuroimage.2015.03.039Neuroimage116168-176GUSTO (Growing up towards Healthy Outcomes

Eye size and shape in newborn children and their relation to axial length and refraction at 3 years

10.1111/opo.12212Ophthalmic and Physiological Optics354414-423GUSTO (Growing up towards Healthy Outcomes

Determinants of cord blood adipokines and association with neonatal abdominal adipose tissue distribution

Background Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort. Methods Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed. Results Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only. Conclusions Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.Peer reviewe

Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants

10.1038/tp.2015.3Translational Psychiatry52GUSTO (Growing up towards Healthy Outcomes

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development

MINDMAP : establishing an integrated database infrastructure for research in ageing, mental well-being, and the urban environment

Background: Urbanization and ageing have important implications for public mental health and well-being. Cities pose major challenges for older citizens, but also offer opportunities to develop, test, and implement policies, services, infrastructure, and interventions that promote mental well-being. The MINDMAP project aims to identify the opportunities and challenges posed by urban environmental characteristics for the promotion and management of mental well-being and cognitive function of older individuals. Methods: MINDMAP aims to achieve its research objectives by bringing together longitudinal studies from 11 countries covering over 35 cities linked to databases of area-level environmental exposures and social and urban policy indicators. The infrastructure supporting integration of this data will allow multiple MINDMAP investigators to safely and remotely co-analyse individual-level and area-level data. Individual-level data is derived from baseline and follow-up measurements of ten participating cohort studies and provides information on mental well-being outcomes, sociodemographic variables, health behaviour characteristics, social factors, measures of frailty, physical function indicators, and chronic conditions, as well as blood derived clinical biochemistry-based biomarkers and genetic biomarkers. Area-level information on physical environment characteristics (e.g. green spaces, transportation), socioeconomic and sociodemographic characteristics (e.g. neighbourhood income, residential segregation, residential density), and social environment characteristics (e.g. social cohesion, criminality) and national and urban social policies is derived from publically available sources such as geoportals and administrative databases. The linkage, harmonization, and analysis of data from different sources are being carried out using piloted tools to optimize the validity of the research results and transparency of the methodology. Discussion: MINDMAP is a novel research collaboration that is combining population-based cohort data with publicly available datasets not typically used for ageing and mental well-being research. Integration of various data sources and observational units into a single platform will help to explain the differences in ageing-related mental and cognitive disorders both within as well as between cities in Europe, the US, Canada, and Russia and to assess the causal pathways and interactions between the urban environment and the individual determinants of mental well-being and cognitive ageing in older adults.Peer reviewe

The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate With Early Childhood Adiposity

Context The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. Objective In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years. Methods Liquid chromatography-tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age. Results Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years. Conclusion Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.Peer reviewe

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension

Background: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. Methods: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. Results: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. Conclusion: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. Methods: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEi EDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. Results: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEi EDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEi EDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEi EDV were independent predictors of RV remodelling index. Conclusions: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT03217240

Une comparaison de l'efficacité de différentes bases de numérotation et de différents nombres de bases dans l'application d'une démarche pédagogique développée pour l'apprentissage des "fractions positionnelles

Le mémoire que nous présentons dans les pages qui suivent rapporte la préparation, le déroulement et les résultats d'une expérience sur l'apprentissage des "fractions positionnelles". L'expérience a été organisée de façon à ce qu'il soit possible de comparer différentes bases de numération quant à leur efficacité dans l'acquisition de la connaissance désirée et d'étudier également les avantages possibles d'un entraînement avec plusieurs bases. A la suite d'essais préliminaires, nous avons mis au point quatre séries de fiches d'apprentissage sur les "fractions positionnelles" et nous les avons fait exécuter par cent huit (108) enfants de 10 et 11 ans provenant de quatre classes de cinquième année. Chacun des enfants a travaillé la série de fiches préparée pour le traitement auquel il a été assigné: base trois, base cinq, base dix ou bases trois et cinq. Les résultats analysés sont ceux qui ont été obtenus à un post-test portant sur la connaissance des "fractions positionnelles". Les meilleurs résultats à ce post-test sont obtenus dans le cas du traitement en base cinq. Cependant, 1'expérience ne démontre pas d'une façon significative la meilleure efficacité d'une base relativement â une autre. Quant à la comparaison entre un entraînement avec deux bases et un entraînement avec une seule base, un avantage du premier sur le second est suggéré par l'observation des moyennes obtenues, mais l'analyse de la variance n'indique pas de différences significatives. L'analyse des différents aspects considérés dans l'expérience nous a conduits à la conclusion qu'une bonne connaissance des différents systèmes de numération permet â un enfant d'acquérir une notion nouvelle dans les divers systèmes, avec une économie de temps et de moyens, donc rapidement et efficacement, grâce au transfert d'une base â l'autre qu'il est en mesure d'effectuer