Role of R5 Pyocin in the Predominance of High-Risk Isolates.

Infections with antimicrobial resistant pathogens, such as are a frequent occurrence in healthcare settings. Human infections are predominantly caused by a small number of sequence types (ST), such as ST235, ST111, and ST175. Although ST111 is recognized as one of the most prevalent high-risk clones worldwide and frequently exhibits multidrug-resistant or extensively drug-resistant phenotypes, the basis for this dominance remains unclear.

Long-Term Dominance of Carbapenem-Non-Susceptible ST111 in Hematologic Malignancy Patients and Hematopoietic Cell Transplant Recipients.

An epidemiological study uncovered that fluoroquinolone (FQ) neutropenic prophylaxis in hematopoietic cell transplant and hematologic malignancy (HCT/HM) patients was associated with breakthrough bloodstream infections (BSIs) with isolates non-susceptible to both FQs and meropenem. The molecular epidemiology of the FQ/meropenem-non-susceptible isolates causing FQ-breakthrough BSIs in the HCT/HM patients remains unclear. Through whole genome sequencing on 57 P isolates from 54 patients diagnosed with HM or receiving an HCT, we found that ST111 strains predominated, accounting for 22 (38.

Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors.

Objective: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.

Methods: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles.

Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis.

Objectives: The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study.

Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.

Objective: To examine the heterogeneity of global transcriptome patterns in systemic sclerosis (SSc) skin in a large sample of patients with SSc and control subjects.

Methods: Skin biopsy specimens obtained from 61 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 36 unaffected control subjects with a similar demographic background were examined by Illumina HumanHT-12 bead arrays. Followup experiments using quantitative polymerase chain reaction and immunohistochemical analysis were also performed.

Unique temporal and spatial expression patterns of IL-33 in ovaries during ovulation and estrous cycle are associated with ovarian tissue homeostasis.

Ovaries are among the most active organs. Frequently occurring events such as ovulation and ovarian atresia are accompanied with tissue destruction and repairing. Critical roles of immune cells or molecules in those events have been well recognized.

Identification of cadherin 11 as a mediator of dermal fibrosis and possible role in systemic sclerosis.

Objective: Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad-11) expression is increased in the affected skin of patients with SSc. The purpose of this study was to examine our hypothesis that Cad-11 is a mediator of dermal fibrosis.

Secondary use of existing public microarray data to predict outcome for hepatocellular carcinoma.

Background: Since 1990, numerous public repositories of microarray data have been created to store vast genomic data sets. Our hypothesis is that a secondary analysis of an available hepatocellular carcinoma (HCC) public data set could generate new findings and additional hypotheses.

Methods: The Gene Expression Omnibus at the National Center for Biotechnology Information was queried for available data sets specific for 'HCC' and 'clinical data.

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region.

Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.

Objective: We undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc).

Methods: Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis.

New insight on the Xq28 association with systemic sclerosis.

Objective: To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2).

Methods: We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays.

Correlation of interferon-inducible chemokine plasma levels with disease severity in systemic sclerosis.

Objective: To measure interferon (IFN)-inducible chemokines in the plasma of patients with systemic sclerosis (SSc) and investigate whether the chemokine levels are correlated with disease severity.

Methods: Plasma levels of the IFN-inducible chemokines IFNγ-inducible protein 10 (IP-10/CXCL10), IFN-inducible T cell α chemoattractant (I-TAC/CXCL11), and monocyte chemoattractant protein 1 (CCL2) were measured in SSc patients and examined for correlation with the IFN gene expression signature. A composite IFN-inducible chemokine score was generated for chemokines showing a correlation with the IFN gene signature (IP-10 and I-TAC), and this score was compared between 266 patients with SSc enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 97 matched control subjects.

Nucleic acid-containing amyloid fibrils potently induce type I interferon and stimulate systemic autoimmunity.

The immunopathophysiologic development of systemic autoimmunity involves numerous factors through complex mechanisms that are not fully understood. In systemic lupus erythematosus, type I IFN (IFN-I) produced by plasmacytoid dendritic cells (pDCs) critically promotes the autoimmunity through its pleiotropic effects on immune cells. However, the host-derived factors that enable abnormal IFN-I production and initial immune tolerance breakdown are largely unknown.

Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study.

Introduction: A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry.

Methods: 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study.

IRF5 polymorphism predicts prognosis in patients with systemic sclerosis.

Objective: The first genome-wide association study (GWAS) of systemic sclerosis (SSc) demonstrated three non-major histocompatibility complex (MHC) susceptibility loci. The goal of this study was to investigate the impact of these gene variants on survival and severity of interstitial lung disease (ILD) in SSc.

Methods: The authors examined 1443 Caucasian SSc patients enrolled in the Genetics versus Environment In Scleroderma Outcome Study (GENISOS) and Scleroderma Family Registry (n = 914 - discovery cohort) and The Johns Hopkins Scleroderma Cohort (n = 529 - replication cohort).

Osteopontin in systemic sclerosis and its role in dermal fibrosis.

Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Here, we determined whether OPN levels are increased in a large cohort of patients with systemic sclerosis (SSc) and whether OPN contributes to the development of dermal fibrosis.

Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis.

Objective: Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features.

Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts.

Introduction: Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts, a major cell type involved in the fibrotic process.

Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups.

Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts.

Introduction: Increased levels of genes in the type I interferon (IFN) pathway have been observed in patients with systemic sclerosis (SSc), or scleroderma. How type I IFN regulates the dermal fibroblast and its participation in the development of dermal fibrosis is not known. We hypothesized that one mechanism by which type I IFN may contribute to dermal fibrosis is through upregulation of specific Toll-like receptors (TLRs) on dermal fibroblasts.