Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.

Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis.

A prospective clinical study was performed to correlate nasopharyngeal carriage of bacteria with the type of lower respiratory tract infections (LRTI) in hospitalised children. To determine bacterial load in nasopharyngeal aspirates (NPA) we used semiquantitative culturing and quantitative TaqMan-PCR for those pathogens difficult to culture. Specimens and clinical data were obtained from 311 children between 0 and 16 years of age with LRTI during the period of 2006-2008. The most common detected potentially pathogenic colonisers were Haemophilus influenzae (32.1 %), Moraxella catharralis (26.7 %), Staphylococcus aureus (17.7 %) and Streptococcus pneumoniae (16.7 %). As expected S. aureus was the most common coloniser in children less than 4 months of age, whereas H. influenzae detection peaked in older children. Co-colonisation with other bacterial pathogens were more often observed in children with S. aureus (46 %) and S. pneumoniae (49 %) than in those with H. influenzae (30 %) or M. catharralis (27 %). Children with S. aureus co-colonisation had higher levels of C-reactive-protein, received antibiotics more frequently and stayed longer in hospital than those with S. aureus single colonisation. In contrast, children with H. influenzae, M. catharralis or S. pneumoniae colonisation suffered more often from pneumonia than children with S. aureus colonisation. Coloniser specific analysis of bacterial quantity revealed no significant reduction of the bacterial carriage from the first to the second NPA. No correlation of a high bacterial load and occurrence of pneumonia could be detected. In conclusion, clinical characteristics in children with LRTIs are associated with a specific bacterial set of colonisers detected in the nasopharynx rather than on their quantity.

BackgroundAn adverse intrauterine environment leads to permanent physiological changes including vascular tone regulation, potentially influencing the risk for adult vascular diseases. We therefore aimed to monitor responsive NOS3 expression in human umbilical artery endothelial cells (HUAEC) and to study the underlying epigenetic signatures involved in its regulation.ResultsNOS3 and STAT3 mRNA levels were elevated in HUAEC of patients who suffered from placental insufficiency. 5-hydroxymethylcytosine, H3K9ac and Histone 2A (H2A).Zac at the NOS3 transcription start site directly correlated with NOS3 mRNA levels. Concomitantly, we observed entangled histone acetylation patterns and NOS3 response upon hypoxic conditions in vitro. Knock-down of either NOS3 or STAT3 by RNAi provided evidence for a functional NOS3/STAT3 relationship. Moreover, we recognized massive turnover of Stat3 at a discrete binding site in the NOS3 promoter. Interestingly, induced hyperacetylation resulted in short-termed increase of NOS3 mRNA followed by deferred decrease indicating that NOS3 expression could become self-attenuated by co-expressed intronic 27 nt-ncRNA. Reporter assay results and phylogenetic analyses enabled us to propose a novel model for STAT3-3′-UTR targeting by this 27-nt-ncRNA.ConclusionsAn adverse intrauterine environment leads to adaptive changes of NOS3 expression. Apparently, a rapid NOS3 self-limiting response upon ectopic triggers co-exists with longer termed expression changes in response to placental insufficiency involving differential epigenetic signatures. Their persistence might contribute to impaired vascular endothelial response and consequently increase the risk of cardiovascular disease later in life.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-014-0042-4) contains supplementary material, which is available to authorized users.

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