Airway microbiota and immune mediator relationships differ in obesity and asthma.

Background: Asthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without nonsevere asthma is unestablished.

Objective: We compared the airway microbiome and microbiota-immune mediator relationships between obese and nonobese subjects, with and without mild-moderate asthma.

Effects of Fluticasone Propionate on and Gram-Negative Bacteria Associated with Chronic Airway Disease.

Inhaled corticosteroids (ICS) are commonly prescribed first-line treatments for asthma and chronic obstructive pulmonary disease (COPD). Recent evidence has shown that ICS use is associated with changes in the airway microbiome, which may impact clinical outcomes such as potential increased risk for pneumonia in COPD. Although the immunomodulatory effects of corticosteroids are well appreciated, whether ICS could directly influence the behavior of respiratory tract bacteria has been unknown.

Water-Group Pickup Ions From Europa-Genic Neutrals Orbiting Jupiter.

Water-group gas continuously escapes from Jupiter's icy moons to form co-orbiting populations of particles or neutral toroidal clouds. These clouds provide insights into their source moons as they reveal loss processes and compositions of their parent bodies, alter local plasma composition, and act as sources and sinks for magnetospheric particles. We report the first observations of H pickup ions in Jupiter's magnetosphere from 13 to 18 Jovian radii and find a density ratio of H /H = 8 ± 4%, confirming the presence of a neutral H toroidal cloud.

The lung microbiome in end-stage Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease with mortality driven primarily by respiratory failure. Patients with LAM frequently have respiratory infections, suggestive of a dysregulated microbiome. Here we demonstrate that end-stage LAM patients have a distinct microbiome signature compared to patients with end-stage chronic obstructive pulmonary disease.

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes.

Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g.

Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort.

Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF).

Gut microbiota relationships to lung function and adult asthma phenotype: a pilot study.

Introduction: Despite strong evidence that maturation patterns of the gut microbiome in early life influence the risk for childhood asthma, very little is known about gut microbiota patterns in adults with established asthma, and of greater interest relationships to phenotypic features that characterise asthma heterogeneity.

Methods: Fifty-eight faecal samples from 32 adults with (n=24) and without (n=8) asthma were analysed using 16S ribosomal RNA gene sequencing methods to characterise intestinal bacterial composition. Compositional stability of paired samples was evaluated and features of gut bacterial community structure analysed in relation to extensive clinical characterisation data collected from subjects, who were enrolled in a prospective observational cohort study at the University of Michigan.

ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras). We show that partial or total ATM deficiency cooperates with Kras to promote highly metastatic pancreatic cancer.

Strengthening resources for midlife and older rural women who experience intimate partner violence.

Little is known about midlife and older women who experience intimate partner violence living in rural places and their resource needs. Guided by a strengths perspective, we provided insights into resources that midlife and older women use, or would like to use, in their journey in leaving an abusive partner. Eight women who had left an abusive partner participated in a face-to-face interview.

Signaling mechanisms coupled to CXCL12/CXCR4-mediated cellular proliferation are PTEN-dependent.

A key difference between normal and malignant prostate cells in vitro and in vivo is that both alleles of PTEN are largely intact in normal benign prostate glands and cultured epithelial cells, whereas one or both alleles of PTEN are mutant or deleted in the majority of prostate tumors and malignant prostate cancer cell lines. Intact PTEN suppresses phosphorylation of Akt downstream of PI3K activation in non-transformed cells whereas Akt phosphorylation is unimpeded in malignant cells that are often PTEN-deficient. We have previously shown that activation of the CXCL12/CXCR4 axis transactivates the EGFR to promote pro-proliferative signaling preferentially through the Raf/MEK/Erk pathway in benign prostate epithelial cells.

The influence of Driving Status on Transportation Challenges Experienced by Older Adults.

We explored the severity, number, and reasons for transportation challenges experienced by older adult drivers, nondrivers who live with a driver, and nondrivers who do not live with a driver. A random sample of 1,670 Atlantic Canadian community-dwelling older adults completed a mailed survey. Drivers comprised 80% of the participants.

Leukocytic promotion of prostate cellular proliferation.

Background: Histological evidence of pervasive inflammatory infiltrate has been noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer (PCa). Cytokines known to attract particular leukocyte subsets are secreted from prostatic stroma consequent to aging and also from malignant prostate epithelium. Therefore, we hypothesized that leukocytes associated with either acute or chronic inflammation attracted to the prostate consequent to aging or tumorigenesis may promote the abnormal cellular proliferation associated with BPH and PCa.

The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy.

Benign Prostatic Hypertrophy (BPH, also known as benign prostatic hyperplasia or benign prostatic enlargement), is one of the most common benign proliferative conditions associated with aging in men and is pathologically characterized by the proliferation of fibroblast/myofibroblast and epithelial cell types in the prostate. Previous studies from our laboratory have shown that the CXC-type chemokines, CXCL5 and CXCL12, are secreted by aging prostate stroma and promote both proliferative and transcriptional responses from prostate epithelial cells. Using array-based gene expression profiling and quantitative reverse-transcriptase polymerase chain reaction, we now show that the transcriptome of the aging prostate stroma is characterized by the up-regulation of several genes that encode secreted inflammatory mediators, including secreted CXC-type chemokines (CXCL1, CXCL2, CXCL5, CXCL6, CXCL12), interleukins (IL11, IL33), and transcripts with cytokine homology (CYTL1).

CXCL5 promotes prostate cancer progression.

CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype.

Pilot and feasibility study of serum chemokines as markers to distinguish prostatic disease in men with low total serum PSA.

Background: The incidence and prevalence of both benign prostatic hypertrophy (BPH) and prostate cancer (PCa) increase with the aging process. Our laboratory recently showed that the chemokines CXCL5 and CXCL12, which normally function as inflammatory mediators, are secreted at higher levels by aging prostate stromal fibroblasts and elicit proliferative responses from both prostate stromal fibroblast and epithelial cells. Because both CXCL5 and CXCL12 are secreted molecules, we hypothesized that their levels in patient serum might serve as biomarkers to distinguish between BPH and PCa.

CXCL12 activates a robust transcriptional response in human prostate epithelial cells.

CXCL12 is a CXC-type chemokine that plays important roles in hematopoiesis, development, and organization of the immune system and supports the survival or growth of a variety of normal or malignant cell types. Our laboratory recently showed that CXCL12 is secreted by aging stromal fibroblast cells and is a major paracrine factor that specifically stimulates the proliferation of prostate epithelial cells. The current study shows that this CXCL12-mediated proliferative response may be either ERK-dependent or ERK-independent.

CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro.

The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts.

Concordant copy number and transcriptional activity of genes mapping to derivative chromosomes 8 during cellular immortalization in vitro.

Deletion, rearrangement, or amplification of sequences mapping to chromosome 8 are frequently observed in human prostate and other tumors. However, it is not clear whether these events alter the transcriptional activity of the affected genes. To examine this question, we have utilized oligonucleotide microarray technology and compared the transcriptional patterns of normal human prostate tissues and five immortalized cell lines carrying either two normal chromosomes 8 or one normal and one derivative chromosome 8.

'Yarning for better health'. Improving the health of an Aboriginal and Torres Strait Islander population.

Background: For over 2 years--as part of a broader strategy to address the health disadvantages in the Aboriginal and Torres Strait Islander population--Brisbane South Division of General Practice (BSDGP) has been involved in providing community health education to the local indigenous community.

Objective: This article discusses the 'Yarning for better health' program.

Discussion: The program aims to improve the local indigenous population's knowledge of health issues, particularly preventive health, and increase through community education their awareness of the role of the general practitioner.

Evolution of 8p loss in transformed human prostate epithelial cells.

Deletion or rearrangement of sequences that map to the short arm of chromosome 8 (8p) are frequently associated with human prostate tumorigenesis. These losses often involve the entire short arm of chromosome 8 or very large regions of distal or proximal 8p, and several putative tumor suppressor genes mapping to 8p have been described. However, the mechanism responsible for 8p loss during prostate tumorigenesis has not been elucidated.

Efficacy of intravenous clindamycin and methicillin in gram-positive soft tissue infections.

In a comparative study on a general surgical service, intravenous clindamycin phosphate or methicillin was used to treat a variety of soft tissue infections due to gram-positive organisms, chiefly staphylococci. The infections were rated according to severity, responsible organisms, and site of the infection. Excellent or good clinical and bacteriologic responses were obtained with both clindamycin and methicillin as adjuncts to basic surgical therapy in these soft tissue infections.