Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone

Microbial diversity of a meromictic soda lake: seasonal and spatial patterns

Select anaerobic activities and the composition of members of the domain Bacteria in samples from a meromictic soda lake were studied. Summer and fall samples were collected from the mixolimnion, the chemocline, the monimolimnion, and sediment.. Most-probable number assays targeting anaerobic microbial guilds were established. In both seasons, the anoxic samples appeared to be dominated by lactate-oxidizing sulfate-reducing bacteria. Lactate- and acetate-oxidizing iron-reducing bacteria, as well as fermentative microorganisms, were also detected at high numbers, whereas methanogenic numbers were low or undetectable. In addition, community structure was assessed with a culture-independent approach --Abstract, page iii

Spatial and Temporal Patterns in the Microbial Diversity of a Meromictic Soda Lake in Washington State▿ †

The microbial community diversity and composition of meromictic Soap Lake were studied using culture-dependent and culture-independent approaches. The water column and sediments were sampled monthly for a year. Denaturing gradient gel electrophoresis of bacterial and archaeal 16S rRNA genes showed an increase in diversity with depth for both groups. Late-summer samples harbored the highest prokaryotic diversity, and the bacteria exhibited less seasonal variability than the archaea. Most-probable-number assays targeting anaerobic microbial guilds were performed to compare summer and fall samples. In both seasons, the anoxic samples appeared to be dominated by lactate-oxidizing sulfate-reducing prokaryotes. High numbers of lactate- and acetate-oxidizing iron-reducing bacteria, as well as fermentative microorganisms, were also found, whereas the numbers of methanogens were low or methanogens were undetectable. The bacterial community composition of summer and fall samples was also assessed by constructing 16S rRNA gene clone libraries. A total of 508 sequences represented an estimated >1,100 unique operational taxonomic units, most of which were from the monimolimnion, and the summer samples were more diverse than the fall samples (Chao1 = 530 and Chao1 = 295, respectively). For both seasons, the mixolimnion sequences were dominated by Gammaproteobacteria, and the chemocline and monimolimnion libraries were dominated by members of the low-G+C-content group, followed by the Cytophaga-Flexibacter-Bacteroides (CFB) group; the mixolimnion sediments contained sequences related to uncultured members of the Chloroflexi and the CFB group. Community overlap and phylogenetic analyses, however, not only demonstrated that there was a high degree of spatial turnover but also suggested that there was a degree of temporal variability due to differences in the members and structures of the communities

New Insights into the Intrinsic and Extrinsic Factors That Shape the Human Skin Microbiome

Many studies have highlighted the importance of body site and individuality in shaping the composition of the human skin microbiome, but we still have a poor understanding of how extrinsic (e.g., lifestyle) and intrinsic (e.g., age) factors influence its composition. We characterized the bacterial microbiomes of North American volunteers at four skin sites and the mouth. We also collected extensive subject metadata and measured several host physiological parameters. Integration of host and microbial features showed that the skin microbiome was predominantly associated with demographic, lifestyle, and physiological factors. Furthermore, we uncovered reproducible associations between chronological age, skin aging, and members of the genus Corynebacterium. Our work provides new understanding of the role of host selection and lifestyle in shaping skin microbiome composition. It also contributes to a more comprehensive appreciation of the factors that drive interindividual skin microbiome variation.Despite recognition that biogeography and individuality shape the function and composition of the human skin microbiome, we know little about how extrinsic and intrinsic host factors influence its composition. To explore the contributions of these factors to skin microbiome variation, we profiled the bacterial microbiomes of 495 North American subjects (ages, 9 to 78 years) at four skin surfaces plus the oral epithelium using 16S rRNA gene amplicon sequencing. We collected subject metadata, including host physiological parameters, through standardized questionnaires and noninvasive biophysical methods. Using a combination of statistical modeling tools, we found that demographic, lifestyle, and physiological factors collectively explained 12 to 20% of the variability in microbiome composition. The influence of health factors was strongest on the oral microbiome. Associations between host factors and the skin microbiome were generally dominated by operational taxonomic units (OTUs) affiliated with the Clostridiales and Prevotella. A subset of the correlations between microbial features and host attributes were site specific. To further explore the relationship between age and the skin microbiome of the forehead, we trained a Random Forest regression model to predict chronological age from microbial features. Age was associated mostly with two mutually coexcluding Corynebacterium OTUs. Furthermore, skin aging variables (wrinkles and hyperpigmented spots) were independently correlated to these taxa

Nitrincola Lacisaponensis Gen. Nov., Sp. Nov., A Novel Alkaliphilic Bacterium Isolated from an Alkaline, Saline Lake.

A novel alkaliphilic bacterium, strain 4CAT, was isolated from decomposing wood taken from the shore of Soap Lake, a saline, alkaline lake in Grant County, WA, USA. Cells of the isolate were Gram-negative, asporogenous, short, motile rods that utilized only a limited range of organic acids as sole carbon and energy sources. In addition to oxygen, the strain possessed the ability to reduce NO-2 in the presence of acetate. Strain 4CAT was oxidase- and catalase-positive; it degraded Tween 60, but not DNA, urea, gelatin or starch. It grew at pH values from 7·5 to 11·0, with optimum growth occurring at pH 9·0, and growth was observed in NaCl concentrations of 0·2-1·3 M, with optimum growth at 0·8 M NaCl. The optimum temperature for growth was 37 °C. Strain 4CAT was resistant to erythromycin, bacitracin, novobiocin, polymyxin B, neomycin, gentamicin, streptomycin, carbenicillin, rifampicin and tetracycline, and was susceptible to nalidixic acid, chloramphenicol, ampicillin and penicillin. The isolate\u27s 16S rRNA gene sequence indicated that it belonged to the γ-Proteobacteria, showing 90-94 % similarity to its closest relatives. Maximum-likelihood phylogenetic inferences placed strain 4CAT within a novel lineage related to the marine bacterial genera Neptunomonas and Marinobacterium. The DNA G+C content of the isolate was 47·4 mol%. On the basis of genotypic and phenotypic characterization, it was concluded that strain 4CAT should be placed in a separate taxon as a novel genus and species, with the proposed name Nitrincola lacisaponensis gen. nov., sp. nov. The type strain is 4CAT (=ATCC BAA-920T=DSM 16316T)

Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases

Background: Resident gut microbiota are now recognized as potent modifiers of host immune responses in various scenarios. Recently, we demonstrated that perinatal exposure to vancomycin, but not streptomycin, profoundly alters gut microbiota and enhances susceptibility to a TH2 model of allergic asthma. Objective: Here we sought to further clarify the etiology of these changes by determining whether perinatal antibiotic treatment has a similar effect on the TH1/TH17-mediated lung disease, hypersensitivity pneumonitis. Methods: Hypersensitivity pneumonitis was induced in C57BL/6 wild-type or recombination-activating gene 1–deficient mice treated perinatally with vancomycin or streptomycin by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Disease severity was assessed by measuring lung inflammation, pathology, cytokine responses, and serum antibodies. Microbial community analyses were performed on stool samples via 16S ribosomal RNA pyrosequencing and correlations between disease severity and specific bacterial taxa were identified. Results: Surprisingly, in contrast to our findings in an allergic asthma model, we found that the severity of hypersensitivity pneumonitis was unaffected by vancomycin, but increased dramatically after streptomycin treatment. This likely reflects an effect on the adaptive, rather than innate, immune response because the effects of streptomycin were not observed during the early phases of disease and were abrogated in recombination-activating gene 1–deficient mice. Interestingly, Bacteroidetes dominated the intestinal microbiota of streptomycin-treated animals, while vancomycin promoted the expansion of the Firmicutes. Conclusions: Perinatal antibiotics exert highly selective effects on resident gut flora, which, in turn, lead to very specific alterations in susceptibility to TH2- or TH1/TH17-driven lung inflammatory disease

Data from: The host response to the lung microbiome in Chromic Obstructive Pulmonary Disease

Rationale: The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This article examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression. Methods: Culture-independent pyrosequencing microbiome analysis was used to examine the V3–V5 regions of bacterial 16S ribosomal DNA in 40 samples of lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 4) and 28 samples from 4 donors (controls). A second protocol based on the V1–V3 regions was used to verify the bacterial microbiome results. Within lung tissue samples the microbiome was compared with results of micro–computed tomography, infiltrating inflammatory cells measured by quantitative histology, and host gene expression. Measurements and Main Results: Ten operational taxonomic units (OTUs) was found sufficient to discriminate between control and GOLD stage 4 lung tissue, which included known pathogens such as Haemophilus influenzae. We also observed a decline in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and the infiltration of the tissue by CD4+ T cells. Specific OTUs were also associated with neutrophils, eosinophils, and B-cell infiltration (P < 0.05). The expression profiles of 859 genes and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively, at a false discovery rate cutoff of less than 0.1. Conclusions: These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD