Asthma and Chronic Obstructive Pulmonary Disease (COPD) Prevalence and Health Services Use in Ontario Métis: A Population-Based Cohort Study

Introduction

Chronic respiratory diseases cause a significant health and economic burden around the world. In Canada, Aboriginal populations are at increased risk of asthma and chronic obstructive pulmonary disease (COPD). There is little known, however, about these diseases in the Canadian Métis population, who have mixed Aboriginal and European ancestry. A population-based study was conducted to quantify asthma and COPD prevalence and health services use in the Métis population of Ontario, Canada’s largest province.

Methods

The Métis Nation of Ontario Citizenship Registry was linked to provincial health administrative databases to measure and compare burden of asthma and COPD between the Métis and non-Métis populations of Ontario between 2009 and 2012. Asthma and COPD prevalence, health services use (general physician and specialist visits, emergency department visits, hospitalizations), and mortality were measured.

Results

Prevalences of asthma and COPD were 30% and 70% higher, respectively, in the Métis compared to the general Ontario population (p<0.001). General physician and specialist visits were significantly lower in Métis with asthma, while general physician visits for COPD were significantly higher. Emergency department visits and hospitalizations were generally higher for Métis compared to non-Métis with either disease. All-cause mortality in Métis with COPD was 1.3 times higher compared to non-Métis with COPD (p = 0.01).

Conclusion

There is a high burden of asthma and COPD in Ontario Métis, with significant prevalence and acute health services use related to these diseases. Lower rates of physician visits suggest barriers in access to primary care services.     

An ethical issue in biodiversity science: The monitoring of penguins with flipper bands

Individual marking is essential to study the life-history traits of animals and to track them in all kinds of ecological, behavioural or physiological studies. Unlike other birds, penguins cannot be banded on their legs due to their leg joint anatomy and a band is instead fixed around a flipper. However, there is now detailed evidence that flipper-banding has a detrimental impact on individuals. It can severely injure flipper tissues, and the drag effect of their flipper bands results in a higher energy expenditure when birds are moving through the water. It also results in lower efficiency in foraging, since they require longer foraging trips, as well as in lower survival and lower breeding success. Moreover, due to the uncertainty of the rate of band loss, flipper bands induce a scientific bias. These problems, which obviously have serious ethical implications, can be avoided with alternative methods such as radiofrequency identification techniques.     

Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells

Background

Circulating CD34⁺ cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair.

Methodology/Principal Findings

We show that CD34⁺-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34⁺ progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34⁺ cells expressing FKN was identified as an independent variable inversely correlated to CD34⁺ progenitor cell count. We further showed that treatment of CD34⁺ circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression.

Conclusions

Our data highlights a novel mechanism by which FKN expression on CD34⁺ progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.     

Immunogenic properties of archaeal species found in bioaerosols

The etiology of bioaerosol-related pulmonary diseases remains poorly understood. Recently, archaea emerged as prominent airborne components of agricultural environments, but the consequences of airway exposure to archaea remain unknown. Since subcomponents of archaea can be immunogenic, we used a murine model to study the pulmonary immune responses to two archaeal species found in agricultural facilities: Methanobrevibacter smithii (MBS) and Methanosphaera stadtmanae (MSS). Mice were administered intranasally with 6.25, 25 or 100 μg of MBS or MSS, once daily, 3 days a week, for 3 weeks. MSS induced more severe histopathological alterations than MBS with perivascular accumulation of granulocytes, pronounced thickening of the alveolar septa, alveolar macrophages accumulation and increased perivascular mononucleated cell accumulation. Analyses of bronchoalveolar lavage fluids revealed up to 3 times greater leukocyte accumulation with MSS compared to MBS. Instillation of 100 μg of MBS or MSS caused predominant accumulation of monocyte/macrophages (4.5×10(5) and 4.8×10(5) cells/ml respectively) followed by CD4(+) T cells (1.38×10(5) and 1.94×10(5) cells/ml respectively), B cells (0.73×10(5) and 1.28×10(5) cells/ml respectively), and CD8(+) T cells (0.20×10(5) and 0.31×10(5) cells/ml respectively) in the airways. Both archaeal species induced similar titers of antigen-specific IgGs in plasma. MSS but not MBS caused an accumulation of eosinophils and neutrophils in the lungs, which surprisingly, correlated inversely with the size of the inoculum. Stronger immunogenicity of MSS was confirmed by a 3 fold higher accumulation of myeloid dendritic cells in the airways, compared to MBS. Thus, the dose and species of archaea determine the magnitude and nature of the pulmonary immune response. This is the first report of an immunomodulatory role of archaeal species found in bioaerosols.     

Mechanisms Governing the Endosomal Membrane Recruitment of the Core Retromer in Arabidopsis

The retromer complex localizes to endosomal membranes and is involved in protein trafficking. In mammals, it is composed of a dimer of sorting nexins and of the core retromer consisting of vacuolar protein sorting (VPS)26, VPS29, and VPS35. Although homologs of these proteins have been identified in plants, how the plant retromer functions remains elusive. To better understand the role of VPS components in the assembly and function of the core retromer, we characterize here Arabidopsis vps26-null mutants. We show that impaired VPS26 function has a dramatic effect on VPS35 levels and causes severe phenotypic defects similar to those observed in vps29-null mutants. This implies that functions of plant VPS26, VPS29, and VPS35 are tightly linked. Then, by combining live-cell imaging with immunochemical and genetic approaches, we report that VPS35 alone is able to bind to endosomal membranes and plays an essential role in VPS26 and VPS29 membrane recruitment. We also show that the Arabidopsis Rab7 homolog RABG3f participates in the recruitment of the core retromer to the endosomal membrane by interacting with VPS35. Altogether our data provide original information on the molecular interactions that mediate assembly of the core retromer in plants.     

Toward a Computer Assisted Analysis of NOESY Spectra: A Multivariate Data Analysis of an RNA NOESY Spectrum

Abstract

A multivariate data-representation of a portion of the ¹H-NOESY spectrum of an RNA octamer duplex was used to explore the possibility of using Principal Component Analysis and Partial Least Squares Discrimination for pattern recognition. In this case, it is found that the methods can: (i) distinguish slices containing signal from those containing only noise, (ii) locate slices containing overlapping signals, and (iii) in some cases to segregate slices with unique aspects such as those from terminal nucleotides, overlapping signals, purine-H8, pyrimidine-H6 and adenine-H2 containing slices. These properties can easily be included in a scheme to automate spectral analysis. The formulation described here does not distinguish patterns needed to automate sequential assignment of resonances in NOESY spectra of RNA.     

Adenosine 5'-monophosphate challenge elicits a more peripheral airway response than methacholine challenge

Adenosine 5'-monophosphate (AMP) and methacholine are commonly used to assess airway hyperreactivity. However, it is not fully known whether the site of airway constriction primarily involved during challenges with either agent is similar. Using a ventilation distribution test, we investigated whether the constriction induced by each agent involves the lung periphery in a similar fashion. Ventilation distribution was evaluated by the phase III slope (S) of the single-breath washout, using gases with different diffusivities like helium (He) and hexafluorosulfur (SF(6)). A greater postchallenge increase in S(He) reflects alterations at the level of terminal and respiratory bronchioles, while a greater increase in S(SF6) reflects alterations in alveolar ducts, increases to an equal extent reflecting alterations in more proximal airways where gas transport is still convective for both gases. S(SF6) and S(He) were measured in 15 asthma patients before and after airway challenges (20% forced expired volume in 1-s fall) with AMP and methacholine. S(He) increased to a greater extent than S(SF6) after AMP challenge (5.7 vs. 3.7%/l; P = 0.002), with both slopes increasing to an equal extent after methacholine challenge (3.1%/l; P = 0.959). The larger increase in S(He) following AMP challenge suggests distal ventilation impairment up to the level of terminal and respiratory bronchioles. With methacholine, the similar increases in S(He) and S(SF6) suggest a less distal impairment. AMP, therefore, seems to affect more extensively the very peripheral airways, whereas methacholine seems to have an effect on less distal airways.     

Identification of a conserved sequence in flavoproteins essential for the correct conformation and activity of the NADH oxidase NoxE of Lactococcus lactis

Water-forming NADH oxidases (encoded by noxE, nox2, or nox) are flavoproteins generally implicated in the aerobic survival of microaerophilic bacteria, such as lactic acid bacteria. However, some natural Lactococcus lactis strains produce an inactive NoxE. We examined the role of NoxE in the oxygen tolerance of L. lactis in the rich synthetic medium GM17. Inactivation of noxE suppressed 95% of NADH oxidase activity but only slightly affected aerobic growth, oxidative stress resistance, and NAD regeneration. However, noxE inactivation strongly impaired oxygen consumption and mixed-acid fermentation. We found that the A303T mutation is responsible for the loss of activity of a naturally occurring variant of NoxE. Replacement of A303 with T or G or of G307 with S or A by site-directed mutagenesis led to NoxE aggregation and the total loss of activity. We demonstrated that L299 is involved in NoxE activity, probably contributing to positioning flavin adenine dinucleotide (FAD) in the active site. These residues are part of the strongly conserved sequence LA(T)XXAXXXG included in an alpha helix that is present in other flavoprotein disulfide reductase (FDR) family flavoproteins that display very similar three-dimensional structures.