In the course of a hospital management takeover, a microbial outbreak took place in a tertiary neonatal intensive care unit (NICU). Here, we characterize the outbreak and its management. About 4 months prior to takeover, there was a sharp increase in positive isolates for MSSA and multidrug-resistant organisms (MDROs). Simultaneously, the nursing staff sick leave rate increased dramatically which directly correlated with the number of infection/colonization per week (r2 = 0.95, p = 0.02). During the following months we observed several peaks in positive isolates of methicillin-sensitive staphylococcus aureus (MSSA), MDROs and subsequently a vancomycin-resistant enterococcus (VRE) outbreak. Interventional outbreak management measures were only successful after substantial recruitment of additional nursing staff. None of the VRE, but 44% (n = 4) of MDRO and 32% (n = 23) of MSSA colonized infants developed symptomatic infections (p = 0.02). Among the latter, 35% suffered from serious consequences such as osteomyelitis. The most important risk factors for colonization-to-infection progression were low gestational age and birth weight. Nursing staff fluctuation poses a substantial risk for both bacterial colonization and infection in neonates. Comprehensive outbreak management measures are only successful if adequate nursing staff is available. Non resistant strains account for most neonatal infections – possibly due to their limited perception as being harmful.

BackgroundEarly pulmonary oxygen exposure is one of the most important factors implicated in the development of bronchopulmonary dysplasia (BPD).MethodsHere, we analyzed short- and long-term effects of neonatal hyperoxia on NOS3 and STAT3 expression and corresponding epigenetic signatures using a hyperoxia-based mouse model of BPD.ResultsEarly hyperoxia exposure led to a significant increase in NOS3 (median fold change × 2.37, IQR 1.54–3.68) and STAT3 (median fold change × 2.83, IQR 2.21–3.88) mRNA levels in pulmonary endothelial cells with corresponding changes in histone modification patterns such as H2aZac and H3K9ac hyperacetylation at the respective gene loci. No complete restoration in histone signatures at these loci was observed, and responsivity to later hyperoxia was altered in mouse lungs. In vitro, histone signatures in human aortic endothelial cells (HAEC) remained altered for several weeks after an initial long-term exposure to trichostatin A. This was associated with a substantial increase in baseline eNOS (median 27.2, IQR 22.3–35.6) and STAT3α (median 5.8, IQR 4.8–7.3) mRNA levels with a subsequent significant reduction in eNOS expression upon exposure to hypoxia.ConclusionsEarly hyperoxia induced permanent changes in histones signatures at the NOS3 and STAT3 gene locus might partly explain the altered vascular response patterns in children with BPD.

Figure 1 (A) Pedigree tree: patient (arrow) and known relatives. Red: verified ITGB6G1312A|rs61737764. (B) Immunohistochemistry/H&E stain on parallel target/control tissue sections using anti-human α V β6 (6.2A1) or anti-human LTBP1 (Antibodies Online/ABIN1807165).

/Herdecke University Hospital. Contrary to his brother the boy presented dystrophic at birth (1.715 g birth weight; 150 g below 3rd percentile) and developed adverse gastrointestinal conditions within the first 2 months of life. These included chronic mucosal inflammation and oedematous lamina propria in the intestine, which contributed to intractable diarrhoea. At an age of 7 months the infant eventually died of enteral haemorrhages and liver failure. Further anamnesis revealed several similar fatalities in the familial clan with reportedly frequent parental consanguinity. Intractable chronic diarrhoea in infancy are heterogeneous disorders challenging for diagnostics and therapy. Despite extensive diagnostic approaches the etiology of many cases remains elusive. Investigating putatively underlying genetic disorders might clarify many cases. ResultsTo contribute to the diagnosis we performed whole exome sequencing of the affected infant as well as his twin brother and parents. We identified a suspicious nonsynonymous single nucleotide polymorphism (SNP) in the integrin beta-6 gene (ITGB6G1312A) entailing a V438M substitution. This SNP is very rare in the G1000 cohort and predicted being potentially harmful. The allelic distribution in the genotyped family members fit well with an autosomal recessive inheritance scheme. We performed computational biological and molecular biological analyses on the α V β6 integrin receptor function suggesting that the integrin α V β6 dimerization could be impaired, potentially causing a loss of α V β6 function in wound healing and epithelial tissue integrity. Conclusions Our study provides a starting point for elucidating integrin α V β6 function and for understanding a pathomechanistical relevance of ITGB6V438M. Consent for publicationThe authors have written informed consent from the patients' guardian/parent. Metabolic treatment according to current guideline recommendations has significantly improved neurological outcome. However, cognitive functions have not yet been studied in detail. Methods In a cross-sectional design, 30 patients detected by newborn screening (n = 13), high-risk screening (n = 3) or targeted metabolic testing (n = 14) were studied for simple reaction time (SRT), continuous performance (CP), visual working memory (VWM), visual-motor coordination (Tracking) and visual search (VS). Dystonia (n = 13 patients) was categorized using the Barry-Albright-Dystonia Scale (BADS). Patients were compared with 196 healthy controls. Developmental functions of cognitive performances were analysed using a negative exponential function model. Results BADS scores correlated with speed tests but not with tests measuring stability or higher cognitive functions without time constraints. Developmental functions of GA-I patients significantly differed from controls for SRT and VS but not for VWM and showed obvious trends for CP and Tracking. Dystonic patients were slower in SRT and CP but reached their asymptote of performance similar to asymptomatic patients and controls in all...