Sugar intake of children in the "Childhood Obesity Project" trial

Introduction: High sugar intake has been suggested to be involved in the development of overweight and obesity and several associated NCDs such as diabetes and CVD. The aim of this doctoral thesis is to investigate whether a higher sugar intake in children is associated with two different risk factors of NCDs, i.e. overweight and obesity, and unfavorable blood markers of lipid and glucose metabolism. Methods: Data was drawn from the CHOP trial, a randomized controlled nutritional intervention trial in the first year of life with long- term follow-up. Infants from five European countries (Belgium, Germany, Italy, Poland, Spain) were randomized to feeding with a higher or lower protein content formula, and an additional breastfed reference group was recruited. Nutrition was assessed yearly from 2 to 6 years of age and again at age 8 years using 3-day-weighed food protocols. Anthropometric measurements were taken from 2 to 8 years of age, at the same time as nutrition assessments. A longitudinal analysis was performed to investigate the influence of sugar intake on age and gender standardized body mass index (BMI) and fat mass index (FMI) over time. A cross-sectional analysis at 8 years of age examined the association of sugar intake with several blood markers of lipid and glucose metabolism. Results: While increasing TS intake in an ad libitum diet was positively associated with BMI and FMI z-score, a negative association was observed on an energy-equivalent basis (zBMI: -0.033; 95% CI: -0.061, -0.005, zFMI: - 0.050; 95% CI: - 0.089, - 0.011 at an increase of 100 kcal from TS). Looking at blood markers, an increased consumption of 100 kcal from TS was significantly associated with a HDL-C z-score decrease (-0.14; 95% CI: -0.01, - 0.27). Increase of TS intake from SSBs showed the strongest association with a decrease in HDL-C z-score (-1.67; 95% CI: -0.42, -2.91). For none of the other investigated markers of lipid or glucose metabolism a significant association with TS increase or TS increase of major food groups was observed. Conclusions: Results indicate that increasing TS intake in childhood does not affect overweight or obesity on an energy-equivalent basis. Additionally, on an energy-equivalent basis only HDL-C was unfavorably influenced by increasing TS intake and this association was very weak. The analysis of the current thesis suggests that increasing TS on an energy-equivalent basis in childhood have little impact on the investigated risk factors of NCDs. Therefore, for prevention of NCD risk factors in early childhood the reduction of TEI should be rather focused on. Nevertheless, a diet with a high sugar intake is generally not recommended, since dietary products with high sugar intake, especially with free sugars, are often accompanied by a low nutritional density and add unnecessary and dispensable energy

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Transforming growth factor-beta 2 heterozygous mutant mice exhibit Cowper's gland hyperplasia and cystic dilations of the gland ducts (Cowper's syringoceles)

Analyses of mutant mice with a deletion for the transforming growth factor beta 2 (Tgfβ2) gene revealed cysts in the perineal/scrotal region of male mice. We present evidence from in situ, light and electron microscopy that the cysts observed in Tgfβ2(+/−) heterozygous mice males derive from Cowper's glandtissue. The Cowper's glands of Tgfβ2(+/−) heterozygous mutant mice display all steps of glandular hyperplasiaand cystic dilation. TGF-β isoforms and TGF-β receptor (TβR-II) were localized immunocytochemicallyin sections of Cowper's glands. TGF-ββ2 and TGF-β3 were located predominantly inmyoepithelial cells of the Cowper's gland whereas the TβRII was found in the plasma membrane of the acinar cells. TUNEL-assays revealed that apoptotic cell death is significantly reduced in Cowper's glands of Tgfβ2(+/−) heterozygous mutant mice. The fact that Tgfβ2(+/−) heterozygous mutant mice exhibit hyperplasia of Cowper's gland epithelium and Cowper's gland cysts suggests a disturbance of epithelial–stromal interaction mostlikely due to reduced TGF-β2 level, accompanied by a significant decrease in apoptosis

Immunhistochemische Studien zur fetalen Entwicklung der Innervation und der Verteilung neuroendokriner Zellen und neuroepithelialer Körperchen in der menschlichen Lunge.

Ausgangspunkt dieser Studie ist die Frage nach der Herkunft der neuroendokrinen Zellen und neuroepithelialen Körperchen sowie die Entwicklung der Innervation in der fetalen Lunge des Menschen. Immunhistochemisch wurden Embryonen und Feten zwischen 30 mm und 110 mm Schädel-Steißbein-Länge mit verschiedenen Primärantikörpern gegen neuroendokrine Zellen (z.B. Chromogranin A, PGP 9.5 und Bombesin)und Nerven (z.B.PGP 9.5) bearbeitet und die Ergebnisse deskriptiv ausgewertet. Bombesin-reaktive neuroendokrine Zellen finden sich früher im Epithel der kleineren Bronchiolen im Vergleich zu CgA-reaktiven neuroendokrine Zellen. Zu einem späteren Zeitpunkt zeigen sich immunreaktive Zellansammlungen um die Bronchien und Bronchiolen im Lungenparenchym, während zeitgleich die Zahl der neuroendokrinen Zellen im Epithel zurückgeht. Neuroepitheliale Körperchen finden sich bei keinem Primärantikörper im Epithel. Bei den Untersuchungen mit PGP 9.5 finden sich keine einzelnen neuroendokrinen Zellen im Stroma der Lunge, lediglich Ansammlungen von immunreaktiven Zellen sind im Stroma vorhanden. Eine Differenzierung, ob es sich dabei um extraepitheliale Körperchen oder peribronchiale Ganglien handelt, ist nicht möglich. Schon beim Homo 30 mm lassen sich einzelne Nervenfasern im Stroma der Lunge nachweisen. Neurale Elemente wandern somit schon früh in die Lunge ein. Zu einem späteren Zeitpunkt finden sich dann Ganglien peribronchial. Einen direkten Kontakt der Nervenfasern zu den neuroendokrinen Zellen im Epithel kann diese Untersuchung nicht zeigen. Die Präsenz des cholinergen Systems lässt sich mit Hilfe der Antikörper VMAT und VAChT in der Lunge nachweisen. Eine endgültige Klärung über die Herkunft der neuroendokrinen Zellen in der Lunge konnten diese Untersuchungen nicht erbringen, da hier weiterhin sowohl die autochthone Theorie als auch die Neuralleisten-Theorie möglich sind. Es sind weitere Studien an früheren Embryonen notwendig, um zu klären, ob neuroendokrine Zellen vor neuralen Elementen in der Lunge nachweisbar sind oder nicht. Eine neue Frage werfen die extraepithelialen Zellansammlungen auf. Handelt es sich hierbei um eine Art extraepithelialer Körperchen? Auch hier könnten weitere Untersuchungen Aufschluss geben