Non-Typhi Salmonella gastroenteritis in children presenting to the emergency department: characteristics of patients with associated bacteraemia

ABSTRACTThe records of children with Salmonella gastroenteritis only (n = 97), and those with associated bacteraemia (n = 64), seen in one medical centre during a 12-year period, were analysed retrospectively. Mean patient age was 2.24 ± 2.8 years (range, 0.05–16 years), and 49% were male. Children with bacteraemia presented after a longer duration of symptoms (7.0 ± 6.9 vs. 3.9 ± 4.6 days, p 0.0002), and had higher erythrocyte sedimentation rates (45 ± 22 vs. 33 ± 22 mm/h, p < 0.02) and lactate dehydrogenase values (924 ± 113 vs. 685 ± 165 IU/L, p 0.001). There was a trend in bacteraemic children towards immunosuppression (6.3% vs. 1.0%, p 0.08) and a lower number of siblings (2.9 ± 1.9 vs. 3.8 ± 2.7, p 0.063). Non-bacteraemic children had a more severe clinical appearance, and a higher percentage had a moderate to bad general appearance (51.5 vs. 29.7%, p < 0.01), with dehydration (37.1 vs. 18.8%, p 0.02) and vomiting (58.8 vs. 39.0%, p 0.02). Laboratory dehydration indicators were also markedly worse in non-bacteraemic children, with urine specific gravity of 1020 ± 9.4 vs. 1013 ± 9.0 (p 0.0002), base excess of −4.2 ± 3.0 vs. −2.5 ± 3.4 mEq/L (p 0.01), and blood urea nitrogen of 10.1 ± 7.0 vs. 7.4 ± 4.5 mg% (p 0.002). Thus, the clinical presentation of bacteraemic children was more gradual, and associated gastroenteritis and dehydration was less pronounced. These findings may contribute in part to the inadvertent discharge of bacteraemic children from the emergency department

Toward an Unsteady Aerodynamic ROM for Multiple Mach Regimes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97065/1/AIAA2012-1708.pd

The former companion of the hyper-velocity star S5-HVS1

The hyper-velocity star S5-HVS1, ejected 5 Myr ago from the Galactic Center at 1800 km/s, was most likely produced by tidal break-up of a tight binary by the supermassive black hole SgrA*. Taking a Monte Carlo approach, we show that the former companion of S5-HVS1 was likely a main-sequence star between 1.5 and 6M⊙ and was captured into a highly eccentric orbit with pericenter distance in the range 1-10 AU and semimajor axis about 10³ AU. We then explore the fate of the captured star. We find that the heat deposited by tidally excited stellar oscillation modes leads to runaway disruption if the pericenter distance is smaller than about 3 AU. Over the past 5 Myr, its angular momentum has been significantly modified by orbital relaxation, which may stochastically drive the pericenter inwards below 3 AU and cause tidal disruption. We find an overall survival probability in the range 5% to 50%, depending on the local relaxation time in the close environment of the captured star, and the initial pericenter at capture. The pericenter distance of the surviving star has migrated to 10-100 AU, making it potentially the most extreme member of the S-star cluster. From the ejection rate of S5-HVS1-like stars, we estimate that there may currently be a few stars in such highly eccentric orbits. They should be detectable (typically K_s ≾18.5 mag) by the GRAVITY instrument and by future Extremely Large Telescopes and hence provide an extraordinary probe of the spin of SgrA*

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease

Background - The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. From a cohort of 318 infants, <32 weeks gestation, we selected 7 infants who developed NEC (defined rigorously) and 28 matched controls. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease. Results - A core community of Klebsiella, Escherichia, Staphyloccocus, and Enterococcus was present in all samples. Gut microbiota profiles grouped into six distinct clusters, termed preterm gut community types (PGCTs). Each PGCT reflected dominance by the core operational taxonomic units (OTUs), except of PGCT 6, which had high diversity and was dominant in bifidobacteria. While PGCTs 1–5 were present in infants prior to NEC diagnosis, PGCT 6 was comprised exclusively of healthy samples. NEC infants had significantly more PGCT transitions prior to diagnosis. Metabolomic profiling identified significant pathways associated with NEC onset, with metabolites involved in linoleate metabolism significantly associated with NEC diagnosis. Notably, metabolites associated with NEC were the lowest in PGCT 6. Conclusions - This is the first study to integrate sequence and metabolomic stool analysis in preterm neonates, demonstrating that NEC does not have a uniform microbial signature. However, a diverse gut microbiome with a high abundance of bifidobacteria may protect preterm infants from disease. These results may inform biomarker development and improve understanding of gut-mediated mechanisms of NEC

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions