Fetal and neonatal environment:effects on bile acid and lipid metabolism

Ondervoeding van de foetus kan het risico op chronische aandoeningen als diabetes, obesitas, hart- en vaatziekten en een verstoorde vetstofwisseling verhogen. Dit verband tussen prenatale voeding en ontwikkeling van ziekten op latere leeftijd wordt ook wel ‘metabolic programming’ genoemd. Inzicht in het mechanisme van metabolic programming zou kunnen leiden tot specifieke vroege voedingsstrategieën die de gezondheid in de volwassenheid positief beïnvloeden. Hester van Meer onderzocht het effect van verschillende voedings- of farmacologische manipulaties tijdens de foetale periode op de vetstofwisseling. Door zwangere muizen op een eiwitarm dieet te zetten, onderzocht Van Meer de stofwisseling van de nakomelingen. Het dieet tijdens de zwangerschap bleek geen effect te hebben op het transport van cholesterol van moeder naar foetus in muizen, of op de vetstofwisseling in de foetus in de laatste fase van de zwangerschap. In mensen leidt groeivertraging in de baarmoeder niet tot significante aanpassingen in de foetale vetstofwisseling, zoals de aanmaak van cholesterol en van vetzuren, zo stelt Van Meer verder vast. Het toedienen van een farmacologische stof die de werking activeert van LXR (een belangrijke regulator van het cholesterol- en vetmetabolisme) aan zwangere muizen leidde in de muizenfoetussen tot sterke veranderingen op het vetmetabolisme. Deze werken echter nauwelijks door tot in de jongvolwassenheid. De studies tonen aan dat langetermijneffecten van ondervoeding van de foetus op de vetstofwisseling niet verklaard worden door foetale aanpassingen in de vetstofwisseling

Broadening without Intensification: The Added Value of the European Social and Sectoral Dialogue

The framework of the European social dialogue (ESD) has enabled interest organizations at the European level to conclude agreements on a wide range of social policy issues. This applies both at the inter-sectoral level and within the various sectors, and has led in the last few decades to the creation of a large number of joint texts. This article addresses the issue of the added value of these results for the parties concluding them. It is argued that the ESD does not constitute a system of industrial relations at the European level, but serves as an alternative lobbying channel for the social partners involved

Down syndrome and aberrant right subclavian artery

Down syndrome (DS) may be associated with various organ system disorders. Feeding problems are frequent in children with DS and may be caused by associated defects, including congenital heart defects, gastrointestinal defects, or endocrine disorders. In the absence of these associated conditions, feeding problems are often attributed to general hypotonia. However, an aberrant right subclavian artery (ARSA), a rare vascular anomaly and an unusual cause of problems with the passage of solid food through the esophagus, has recently been suggested to occur more frequently in patients with DS. This knowledge is of importance when evaluating feeding difficulties in patients with DS. Additional investigation for identifying an ARSA may be indicated in selected patients. Diagnostic techniques, such as transthoracic echocardiography, barium contrast esophagram, angiography, or computed tomography–angiography (CT) can be used in a diagnostic flow chart. The presence of ARSA is not synonymous to the cause of feeding problems in patients with DS and corrective surgery of this vascular anomaly should be restricted to selected cases

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders

Fetal and neonatal environment: effects on bile acid and lipid metabolism

Ondervoeding van de foetus kan het risico op chronische aandoeningen als diabetes, obesitas, hart- en vaatziekten en een verstoorde vetstofwisseling verhogen. Dit verband tussen prenatale voeding en ontwikkeling van ziekten op latere leeftijd wordt ook wel ‘metabolic programming’ genoemd. Inzicht in het mechanisme van metabolic programming zou kunnen leiden tot specifieke vroege voedingsstrategieën die de gezondheid in de volwassenheid positief beïnvloeden. Hester van Meer onderzocht het effect van verschillende voedings- of farmacologische manipulaties tijdens de foetale periode op de vetstofwisseling. Door zwangere muizen op een eiwitarm dieet te zetten, onderzocht Van Meer de stofwisseling van de nakomelingen. Het dieet tijdens de zwangerschap bleek geen effect te hebben op het transport van cholesterol van moeder naar foetus in muizen, of op de vetstofwisseling in de foetus in de laatste fase van de zwangerschap. In mensen leidt groeivertraging in de baarmoeder niet tot significante aanpassingen in de foetale vetstofwisseling, zoals de aanmaak van cholesterol en van vetzuren, zo stelt Van Meer verder vast. Het toedienen van een farmacologische stof die de werking activeert van LXR (een belangrijke regulator van het cholesterol- en vetmetabolisme) aan zwangere muizen leidde in de muizenfoetussen tot sterke veranderingen op het vetmetabolisme. Deze werken echter nauwelijks door tot in de jongvolwassenheid. De studies tonen aan dat langetermijneffecten van ondervoeding van de foetus op de vetstofwisseling niet verklaard worden door foetale aanpassingen in de vetstofwisseling. Epidemiological data associate adult disease to factors in the fetal- and early postnatal environment. Maternal gestational under-nutrition affects the offspring’s adult lipid metabolism. This association between fetal environment and adult disease is called “metabolic programming”. Knowledge about the pathophysiological mechanisms of metabolic programming can be relevant to improve long-term health through early preventive nutritional manipulations. Using stable-isotope-techniques we studied the consequences of, and mechanisms underlying dietary- and pharmacological interventions during prenatal life on the lipid metabolism. In mice, fetal under-nutrition did not affect maternal-fetal cholesterol transport or the biosynthesis of cholesterol or fatty-acids in the last stage of gestation. In human infants, intrauterine-growth-restriction did not substantially affect the synthesis rates of lipids. The Liver-X-Receptor (LXR), an important regulator of lipid metabolism, is active in the fetal liver and can be stimulated pharmacologically by administration of an agonist in the diet of pregnant mice. Pharmacological LXR activation affected lipid metabolism in the fetal offspring in mice, without substantially affecting the lipid metabolism in the offspring in adulthood. Overall, we showed that our stable-isotope-methodology allows the determination of effects of the maternal environment on the lipid metabolism in the murine fetus and in small infants. Our results indicate that fetal malnutrition does not lead to profound adaptations in the fetal lipid metabolism. Adaptations in fetal lipid metabolism, initiated by pharmacological LXR activation, do not sustain into adulthood. These findings do not support the hypothesis that effects of the fetal environment on adult lipid metabolism are mediated by adaptations in the fetal lipid metabolism.

The Effects of Intrauterine Malnutrition on Maternal-Fetal Cholesterol Transport and Fetal Lipid Synthesis in Mice

Intrauterine malnutrition is associated with increased susceptibility to chronic diseases in adulthood. Growth-restricted infants display a less favorable lipid profile already shortly postnatal. Maternal low protein diet (LPD) during gestation is a well-defined model of fetal programming in rodents and affects lipid metabolism of the offspring. Effects of LPD throughout gestation on physiologic relevant parameters of lipid metabolism are unclear. We aimed to determine effects of LPD on maternal-fetal cholesterol fluxes and fetal lipid synthesis in mice. Pregnant mice (dams) were fed with a control (18% casein) or an LPD (9% casein) from E0.5 onward. We quantified maternal-fetal cholesterol transport and maternal cholesterol absorption at E19.5 using stable isotopes. We determined fetal lipid biosynthesis at E19.5, after administration of (1-(13)C)-acetate from E17.5 onward. LPD did not change fetal and maternal plasma and hepatic concentrations of cholesterol and triglycerides. LPD affected neither the magnitudes of maternal-fetal cholesterol flux, maternal cholesterol absorption, nor fetal synthesis of cholesterol and palmitate (both groups, similar to 14% and similar to 13%, respectively). We conclude that LPD throughout gestation in mice does not affect maternal-fetal cholesterol transport, fetal cholesterol or fatty acid synthesis, indicating that programming effects of LPD are not mediated by short-term changes in maternal-fetal lipid metabolism. (Pediatr Res 68: 10-15, 2010