Association between respiratory tract diseases and secondhand smoke exposure among never smoking flight attendants: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Little is known about long-term adverse health consequences experienced by flight attendants exposed to secondhand smoke (SHS) during the time smoking was allowed on airplanes. We undertook this study to evaluate the association between accumulated flight time in smoky airplane cabins and respiratory tract diseases in a cohort of never smoking flight attendants.</p> <p>Methods</p> <p>We conducted a mailed survey in a cohort of flight attendants. Of 15,000 mailed questionnaires, 2053 (14%) were completed and returned. We excluded respondents with a personal history of smoking (n = 748) and non smokers with a history of respiratory tract diseases before the age of 18 years (n = 298). The remaining 1007 respondents form the study sample.</p> <p>Results</p> <p>The overall study sample was predominantly white (86%) and female (89%), with a mean age of 54 years. Overall, 69.7% of the respondents were diagnosed with at least one respiratory tract disease. Among these respondents, 43.4% reported a diagnosis of sinusitis, 40.3% allergies, 30.8% bronchitis, 23.2% middle ear infections, 13.6% asthma, 13.4% hay fever, 12.5% pneumonia, and 2.0% chronic obstructive pulmonary disease. More hours in a smoky cabin were observed to be significantly associated with sinusitis (OR = 1.21; p = 0.024), middle ear infections (OR = 1.30; p = 0.006), and asthma (OR = 1.26; p = 0.042).</p> <p>Conclusion</p> <p>We observed a significant association between hours of smoky cabin exposure and self-reported reported sinusitis, middle ear infections, and asthma. Our findings suggest a dose-response between duration of SHS exposure and diseases of the respiratory tract. Our findings add additional evidence to the growing body of knowledge supporting the need for widespread implementation of clean indoor air policies to decrease the risk of adverse health consequences experienced by never smokers exposed to SHS.</p

Individual and Contextual Factors Associated with Low Childhood Immunisation Coverage in Sub-Saharan Africa: A Multilevel Analysis

Background: In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and Findings: We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12–23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. Conclusion: We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live

Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension.

Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH

The Effect of Selenium Supplementation in the Prevention of DNA Damage in White Blood Cells of Hemodialyzed Patients: A Pilot Study

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA

Toolbox for Non-Intrusive Structural and Functional Analysis of Recombinant VLP Based Vaccines: A Case Study with Hepatitis B Vaccine

Background: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccine. Methodology: The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR) and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA). The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM) and in-solution atomic force microscopy (AFM). Principal Findings: SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turnaround, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images – confirming the previously proposed octahedral structure and the established lipidto-protei

Abundance of the Quorum-Sensing Factor Ax21 in Four Strains of Stenotrophomonas maltophilia Correlates with Mortality Rate in a New Zebrafish Model of Infection

Stenotrophomonas maltophilia is a Gram-negative pathogen with emerging nosocomial incidence. Little is known about its pathogenesis and the genomic diversity exhibited by clinical isolates complicates the study of pathogenicity and virulence factors. Here, we present a strategy to identify such factors in new clinical isolates of S. maltophilia, incorporating an adult-zebrafish model of S. maltophilia infection to evaluate relative virulence coupled to 2D difference gel electrophoresis to explore underlying differences in protein expression. In this study we report upon three recent clinical isolates and use the collection strain ATCC13637 as a reference. The adult-zebrafish model shows discrimination capacity, i.e. from very low to very high mortality rates, with clinical symptoms very similar to those observed in natural S. maltophilia infections in fish. Strain virulence correlates with resistance to human serum, in agreement with previous studies in mouse and rat and therefore supporting zebrafish as a replacement model. Despite its clinical origin, the collection strain ATCC13637 showed obvious signs of attenuation in zebrafish, with null mortality. Multilocus-sequence-typing analysis revealed that the most virulent strains, UV74 and M30, exhibit the strongest genetic similitude. Differential proteomic analysis led to the identification of 38 proteins with significantly different abundance in the three clinical strains relative to the reference strain. Orthologs of several of these proteins have been already reported to have a role in pathogenesis, virulence or resistance mechanisms thus supporting our strategy. Proof of concept is further provided by protein Ax21, whose abundance is shown here to be directly proportional to mortality in the zebrafish infection model. Indeed, recent studies have demonstrated that this protein is a quorum-sensing-related virulence factor

Differential preservation of endogenous human and microbial DNA in dental calculus and dentin

Dental calculus (calcified dental plaque) is prevalent in archaeological skeletal collections and is a rich source of oral microbiome and host-derived ancient biomolecules. Recently, it has been proposed that dental calculus may provide a more robust environment for DNA preservation than other skeletal remains, but this has not been systematically tested. In this study, shotgun-sequenced data from paired dental calculus and dentin samples from 48 globally distributed individuals are compared using a metagenomic approach. Overall, we find DNA from dental calculus is consistently more abundant and less contaminated than DNA from dentin. The majority of DNA in dental calculus is microbial and originates from the oral microbiome; however, a small but consistent proportion of DNA (mean 0.08 ± 0.08%, range 0.007–0.47%) derives from the host genome. Host DNA content within dentin is variable (mean 13.70 ± 18.62%, range 0.003–70.14%), and for a subset of dentin samples (15.21%), oral bacteria contribute \u3e 20% of total DNA. Human DNA in dental calculus is highly fragmented, and is consistently shorter than both microbial DNA in dental calculus and human DNA in paired dentin samples. Finally, we find that microbial DNA fragmentation patterns are associated with guanine-cytosine (GC) content, but not aspects of cellular structure

Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae

Zinc is an essential nutrient because it is a required cofactor for many enzymes and transcription factors. To discover genes and processes in yeast that are required for growth when zinc is limiting, we used genome-wide functional profiling. Mixed pools of ∼4,600 deletion mutants were inoculated into zinc-replete and zinc-limiting media. These cells were grown for several generations, and the prevalence of each mutant in the pool was then determined by microarray analysis. As a result, we identified more than 400 different genes required for optimal growth under zinc-limiting conditions. Among these were several targets of the Zap1 zinc-responsive transcription factor. Their importance is consistent with their up-regulation by Zap1 in low zinc. We also identified genes that implicate Zap1-independent processes as important. These include endoplasmic reticulum function, oxidative stress resistance, vesicular trafficking, peroxisome biogenesis, and chromatin modification. Our studies also indicated the critical role of macroautophagy in low zinc growth. Finally, as a result of our analysis, we discovered a previously unknown role for the ICE2 gene in maintaining ER zinc homeostasis. Thus, functional profiling has provided many new insights into genes and processes that are needed for cells to thrive under the stress of zinc deficiency

The Staphylococcus aureus RNome and Its Commitment to Virulence

Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity

Does physical activity change predict functional recovery in low back pain? Protocol for a prospective cohort study

Background: Activity advice and prescription are commonly used in the management of low back pain (LBP). Although there is evidence for advising patients with LBP to remain active, facilitating both recovery and return to work, to date no research has assessed whether objective measurements of free living physical activity (PA) can predict outcome, recovery and course of LBP. Methods: An observational longitudinal study will investigate PA levels in a cohort of community-dwelling working age adults with acute and sub-acute LBP. Each participant's PA level, functional status, mood, fear avoidance behaviours, and levels of pain, psychological distress and occupational activity will be measured on three occasions during for 1 week periods at baseline, 3 months, and 1 year. Physical activity levels will be measured by self report, RT3 triaxial accelerometer, and activity recall questionnaires. The primary outcome measure of functional recovery will be the Roland Morris Disability Questionnaire (RMDQ). Free living PA levels and changes in functional status will be quantified in order to look at predictive relationships between levels and changes in free living PA and functional recovery in a LBP population. Discussion: This research will investigate levels and changes in activity levels of an acute LBP cohort and the predictive relationship to LBP recovery. The results will assess whether occupational, psychological and behavioural factors affect the relationship between free living PA and LBP recovery. Results from this research will help to determine the strength of evidence supporting international guidelines that recommend restoration of normal activity in managing LBP. Trial registration. [Clinical Trial Registration Number, ACTRN12609000282280]. © 2009 Hendrick et al; licensee BioMed Central Ltd