Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study.

The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings

The evidence of contaminants in dairy products

U pogledu zdravstvene ispravnosti namirnica danas se u svijetu poglavito govori o razini njihova zagađenja odnosno nalazu štetnih tvari koje mogu ugroziti čovječje zdravlje. Uporaba veterinarskih lijekova u terapijske svrhe i njihov dodatak stočnoj hrani te uporaba kemijskih sredstava u zaštiti bilja najznačajniji su putovi kemijskog zagađenja mlijeka i mliječnih proizvoda. Razina spomenutih zagađenja ovisi o mogućnostima uporabe tih sredstava u poljoprivrednoj, stočarskoj i veterinarskoj praksi. Zdravstvena ispravnost mliječnih proizvoda ovisi i o nazočnosti patogenih mikroorganizama, a i o suvremenim spoznajama o nutricionističkoj vrijednosti pojedinih sastojaka.In the context of the wholesomeness the foodstuffs today we talk mostly about the quantity of different food contaminants which can cause the disturbances of human health. The use of veterinary drugs for therapeutic purposes and their addition to the animal feed, the use of pesticides and other chemicals in the plant production are the most important ways of milk and dairy products contamination. The quantity of such pollution depends on the possibilities of using this agents in agriculture, animal breeding and veterinary practice. The wholesomeness of dairy products depends on the evidence of pathogenic microorganisms as well as on the nutrition value of the composition of fooodstuffs

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Three dimensional acinar cultures of mammary epithelium as an in vitro model for studying hormonal mechanisms in the mammary gland

Background: Three dimensional (3D) acinar cultures from primary mammary epithelial cells have been used as in vitro strategies to study mammary growth and differentiation. Primary epithelial cells cultured on a reconstituted basement membrane matrix are able to form functional alveolar-like multicellular structures with a luminal compartment and to secrete milk proteins in a vectorial manner. However, the validation of 3D acinar cultures for elucidating functional mammary development requires the study of the hormone dependence of growth and differentiation of acini in vitro. Aim: The aim of this study was to characterize the hormone dependence of growth and functional differentiation of acinar cultures derived from the pregnant gland, with emphasis on insulin. Methods: Acini are dissociated by collagenase digestion of #4 and 5 mammary glands from 14 day pregnant CD1 mice. In some experiments organoids were treated with trypsin and filtered through a 70 um cell strainer to obtain single cells. Organoids or single cells are grown embedded in 100% Matrigel in the following growth medium: DMEM-F12 with insulin (concentrations tested: 870 nM, 100 nM, 50 nM), EGF (5 ng/ml), Prolactin (PRL; 3 ug/ml), hydrocortisone (HC; 1 ug/ml) and fetal bovine serum (FBS; 5%). After one week in culture, the EGF and serum are removed to obtain differentiation medium. After another week, acini are fixed, embedded in paraffin and sectioned. Immunohistochemistry is carried out using primary antibodies for casein and ADPH. Results: In standard culture in differentiation medium, staining for ADPH and casein revealed CLD formation and movement of casein from the cytoplasm to the lumen. Removal of PRL from the differentiation medium resulted in smaller CLD and reduced casein, while removal of HC resulted in casein remaining in the cytoplasm. Insulin was required to support the organization of functional acini from mammary organoids so the omission of insulin resulted in more disordered assemblies showing incomplete lumen formation. Also, the multicellular structures formed from organoids were smaller and fewer in number. Moreover, insulin was required to promote acinar formation starting with single cells. Many acini in good shape were detected with insulin at 870 nM (supraphysiological concentration used in in vitro mammary cultures). A good response was obtained with insulin at 100 and 50 nM as well. Conclusions: Taken together these data demonstrate that 3D acinar cultures respond to hormones as observed in other mammary preparations. They also suggest that this in vitro model will be useful to elucidate signaling pathways utilized by hormones to regulate mammary growth and differentiation in pregnancy. In addition, these results provide evidence that insulin is a critical hormone that supports the organization of mammary epithelial cells in alveolar-like structures, capable of functional differentiation

A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. The relative position of cells along the anterior-posterior axis could also be assigned using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior