The effect of attending steiner schools during childhood on health in adulthood: a multicentre cross-sectional study.

BACKGROUND: It is speculated that attending Steiner schools, whose pedagogical principles include an account for healthy psycho-physical development, may have long-term beneficial health effects. We examined whether the current health status differed between former attendees of German Steiner schools and adults from the general population. Furthermore, we examined factors that might explain those differences. METHODS: We included former Steiner school attendees from 4 schools in Berlin, Hanover, Nuremberg and Stuttgart and randomly selected population controls. Using a self-report questionnaire we assessed sociodemographics, current and childhood lifestyle and health status. Outcomes were self-reports on 16 diseases: atopic dermatitis, allergic rhinitis, bronchial asthma, chronic obstructive pulmonary disease (COPD), cardiac arrhythmia, cardiac insufficiency, angina pectoris, arteriosclerosis, hypertension, hypercholesterolemia, osteoarthritis, rheumatism, cancer, diabetes, depression and multiple sclerosis. Furthermore, participants rated the symptom burden resulting from back pain, cold symptoms, headache, insomnia, joint pain, gastrointestinal symptoms and imbalance. Unadjusted and adjusted odds ratios were calculated for each outcome. RESULTS: 1136 Steiner school attendees and 1746 controls were eligible for analysis. Both groups were comparable regarding sex, age and region, but differed in nationality and educational status. After adjusting for possible confounders, we found statistically significant effects of Steiner school attendance for osteoarthritis (OR 0.69 [0.49-0.97]) and allergic rhinitis (OR 0.77, [0.59-1.00]) as well as for symptom burden from back pain (OR 0.80, [0.64-1.00]), insomnia (OR 0.65, [0.50-0.84]), joint pain (OR 0.62, [0.48-0.82]), gastrointestinal symptoms (OR 0.76, [0.58-1.00]) and imbalance (OR 0.60, [0.38-0.93]). CONCLUSIONS: The risk of most examined diseases did not differ between former Steiner school attendees and the general population after adjustment for sociodemographics, current and childhood lifestyle features, but symptom burden from some current health complaints was reported less by former Steiner school attendees. Results must be interpreted with caution since the analysis was exploratory.

Aberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q.

Myelodysplastic syndromes (MDS) are characterized by abnormal and dysplastic maturation of all blood lineages. Even though epigenetic alterations have been seen in MDS marrow progenitors, very little is known about the molecular alterations in dysplastic peripheral blood cells. We analyzed the methylome of MDS leukocytes by the HELP assay and determined that it was globally distinct from age-matched controls and was characterized by numerous novel, aberrant hypermethylated marks that were located mainly outside of CpG islands and preferentially affected GTPase regulators and other cancer-related pathways. Additionally, array comparative genomic hybridization revealed that novel as well as previously characterized deletions and amplifications could also be visualized in peripheral blood leukocytes, thus potentially reducing the need for bone marrow samples for future studies. Using integrative analysis, potentially pathogenic genes silenced by genetic deletions and aberrant hypermethylation in different patients were identified. DOCK4, a GTPase regulator located in the commonly deleted 7q31 region, was identified by this unbiased approach. Significant hypermethylation and reduced expression of DOCK4 in MDS bone marrow stem cells was observed in two large independent datasets, providing further validation of our findings. Finally, DOCK4 knockdown in primary marrow CD34(+) stem cells led to decreased erythroid colony formation and increased apoptosis, thus recapitulating the bone marrow failure seen in MDS. These findings reveal widespread novel epigenetic alterations in myelodysplastic leukocytes and implicate DOCK4 as a pathogenic gene located on the 7q chromosomal region.

Large-scale identification of essential Salmonella genes by trapping lethal insertions.

A novel screening approach based on insertion-duplication mutagenesis (IDM) was established to efficiently screen for essential genes of Salmonella enterica serovar Typhimurium under laboratory conditions. Small, randomly generated genomic fragments were cloned into a conditionally replicating vector, and the resulting library of single Salmonella clones was grown under permissive conditions. Upon switching to non-permissive temperature, discrimination between lethal and non-lethal insertions following homologous recombination allowed the trapping of genes with essential functions. Further characterization of a total of 498 fragments resulting in such lethal knockout revealed 145 known essential genes and 112 functionally characterized or hypothetical genes not yet shown to encode essential genes, among them three Salmonella-specific genes. The essentiality was demonstrated for a prioritised set of 15 putative indispensable genes by creating conditional lethal phenotypes. The results of this large-scale screening indicate that in rich media, the class of Salmonella genes indispensable for growth is composed of approximately 490 genes.