Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine

Варикозное расширение в системе суральных вен: диагностика, лечение, результаты

ВАРИКОЗНОЕ РАСШИРЕНИЕ ВЕН /ДИАГН /ТЕРКРОВЕНОСНЫХ СОСУДОВ БОЛЕЗНИРЕЦИДИВВЕНЫ /ПАТОЛО

Kitchen Concentrations of Fine Particulate Matter and Particle Number Concentration in Households Using Biomass Cookstoves in Rural Honduras

Cooking and heating with solid fuels results in high levels of household air pollutants, including particulate matter (PM); however, limited data exist for size fractions smaller than PM2.5 (diameter less than 2.5 μm). We collected 24-h time-resolved measurements of PM2.5 (n = 27) and particle number concentrations (PNC, average diameter 10–700 nm) (n = 44; 24 with paired PM2.5 and PNC) in homes with wood-burning traditional and Justa (i.e., with an engineered combustion chamber and chimney) cookstoves in rural Honduras. The median 24-h PM2.5 concentration (n = 27) was 79 μg/m3 (interquartile range [IQR]: 44–174 μg/m3); traditional (n = 15): 130 μg/m3 (IQR: 48–250 μg/m3); Justa (n = 12): 66 μg/m3 (IQR: 44–97 μg/m3). The median 24-h PNC (n = 44) was 8.5 × 104 particles (pt)/cm3 (IQR: 3.8 × 104–1.8 × 105 pt/cm3); traditional (n = 27): 1.3 × 105 pt/cm3 (IQR: 3.3 × 104–2.0 × 105 pt/cm3); Justa (n = 17): 6.3 × 104 pt/cm3 (IQR: 4.0 × 104–1.2 × 105 pt/cm3). The 24-h average PM2.5 and particle number concentrations were correlated for the full sample of cookstoves (n = 24, Spearman ρ: 0.83); correlations between PM2.5 and PNC were higher in traditional stove kitchens (n = 12, ρ: 0.93) than in Justa stove kitchens (n = 12, ρ: 0.67). The 24-h average concentrations of PM2.5 and PNC were also correlated with the maximum average concentrations during shorter-term averaging windows of one-, five-, 15-, and 60-min, respectively (Spearman ρ: PM2.5 [0.65, 0.85, 0.82, 0.71], PNC [0.74, 0.86, 0.88, 0.86]). Given the moderate correlations observed between 24-h PM2.5 and PNC and between 24-h and the shorter-term averaging windows within size fractions, investigators may need to consider cost-effectiveness and information gained by measuring both size fractions for the study objective. Further evaluations of other stove and fuel combinations are needed

Parabacteroides distasonis:intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health

Parabacteroides distasonis is the type strain for the genus Parabacteroides, a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as Bacteroides distasonis, the strain was re-classified to form the new genus Parabacteroides in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (P. acidifaciens, P. chartae, P. chinchillae, P. chongii, P. distasonis, P. faecis, P. goldsteinii, P. gordonii, P. johnsonii, and P. merdae) and 5 'not validly named' (P. bouchesdurhonensis, P. massiliensis, P. pacaensis, P. provencensis, and P. timonensis) by the List of Prokaryotic names with Standing in Nomenclature. The Parabacteroides genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of P. distasonis on human and animal health

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection

Evaluating the Dimensionality of First-Grade Written Composition

Purpose—We examined dimensions of written composition using multiple evaluative approaches such as an adapted 6+1 trait scoring, syntactic complexity measures, and productivity measures. We further examined unique relations of oral language and literacy skills to the identified dimensions of written composition. Method—A large sample of first grade students (N = 527) was assessed on their language, reading, spelling, letter writing automaticity, and writing in the spring. Data were analyzed using a latent variable approach including confirmatory factor analysis and structural equation modeling. Results—The seven traits in the 6+1 trait system were best described as two constructs: substantive quality, and spelling and writing conventions. When the other evaluation procedures such as productivity and syntactic complexity indicators were included, four dimensions emerged: substantive quality, productivity, syntactic complexity, and spelling and writing conventions. Language and literacy predictors were differentially related to each dimension in written composition. Conclusions—These four dimensions may be a useful guideline for evaluating developing beginning writer’s compositions

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests