Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology.

Epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes among children conceived using assisted reproductive technology (ART), suggesting that ART procedures may be disruptive to imprinted gene methylation patterns. We examined intra- and inter-individual variation in DNA methylation at the differentially methylated regions (DMRs) of the IGF2/H19 and IGF2R loci in a population of children conceived in vitro or in vivo. We found substantial variation in allele-specific methylation at both loci in both groups. Aberrant methylation of the maternal IGF2/H19 DMR was more common in the in vitro group, and the overall variance was also significantly greater in the in vitro group. We estimated the number of trophoblast stem cells in each group based on approximation of the variance of the binomial distribution of IGF2/H19 methylation ratios, as well as the distribution of X chromosome inactivation scores in placenta. Both of these independent measures indicated that placentas of the in vitro group were derived from fewer stem cells than the in vivo conceived group. Both IGF2 and H19 mRNAs were significantly lower in placenta from the in vitro group. Although average birth weight was lower in the in vitro group, we found no correlation between birth weight and IGF2 or IGF2R transcript levels or the ratio of IGF2/IGF2R transcript levels. Our results show that in vitro conception is associated with aberrant methylation patterns at the IGF2/H19 locus. However, very little of the inter- or intra-individual variation in H19 or IGF2 mRNA levels can be explained by differences in maternal DMR DNA methylation, in contrast to the expectations of current transcriptional imprinting models. Extraembryonic tissues of embryos cultured in vitro appear to be derived from fewer trophoblast stem cells. It is possible that this developmental difference has an effect on placental and fetal growth.

Ergonomic interventions for office workers with musculoskeletal disorders: a systematic review.

INTRODUCTION: Ergonomic interventions designed for office and computer work have become widely available and heavily marketed but there is little evidence to support their use with workers who already have a musculoskeletal disorder (MSD). The purpose of any ergonomic intervention can be to improve worker comfort, safety and/or productivity. The ergonomic research in secondary prevention typically focuses outcomes on improved worker comfort but less if any emphasis has been put on productivity and safety. The purpose of this study was to determine the level and quality of evidence supporting ergonomic interventions to improve the comfort, safety and/or productivity of office workers with symptoms of MSDs. METHOD: A search of the ergonomic intervention literature based on MSDs of four body areas (low back, upper limb, eye and neck) was employed. The studies underwent two levels of analysis for inclusion in a best-evidence synthesis approach, which included a priori evaluation of specific interventions relative to outcomes of comfort, safety and/or productivity. RESULTS: Twenty-seven out of 202 articles were synthesized based on relevance, quality and significant results. Only 8 articles were determined high quality and no strong levels of evidence were identified. Levels of evidence for specific ergonomic interventions ranged from insufficient to moderate. Generally outcomes were focused mostly on improved comfort of workers. CONCLUSIONS: There is still limited quality research that addresses ergonomic interventions designed for secondary prevention. Further high quality studies are needed to support evidence-based ergonomic interventions in practice. For all stakeholders to fully evaluate the usefulness of the ergonomic intervention studies need to attend to outcomes not only of worker comfort but also to productivity and safety.