The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition

Geographical variation in radiological services: a nationwide survey

BACKGROUND: Geographical variation in health care services challenges the basic principle of fair allocation of health care resources. This study aimed to investigate geographical variation in the use of X-ray, CT, MRI and Ultrasound examinations in Norway, the contribution from public and private institutions, and the impact of accessibility and socioeconomic factors on variation in examination rates. METHODS: A nationwide survey of activity in all radiological institutions for the year 2002 was used to compare the rates per thousand of examinations in the counties. The data format was files/printouts where the examinations were recorded according to a code system. RESULTS: Overall rates per thousand of radiological examinations varied by a factor of 2.4. The use of MRI varied from 170 to 2, and CT from 216 to 56 examinations per 1000 inhabitants. Single MRI examinations (knee, cervical spine and head/brain) ranged high in variation, as did certain other spine examinations. For examination of specific organs, the counties' use of one modality was positively correlated with the use of other modalities. Private institutions accounted for 28% of all examinations, and tended towards performing a higher proportion of single examinations with high variability. Indicators of accessibility correlated positively to variation in examination rates, partly due to the figures from the county of Oslo. Correlations between examination rates and socioeconomic factors were also highly influenced by the figures from this county. CONCLUSION: The counties use of radiological services varied substantially, especially CT and MRI examinations. A likely cause of the variation is differences in accessibility. The coexistence of public and private institutions may be a source of variability, along with socioeconomic factors. The findings represent a challenge to the objective of equality in access to health care services, and indicate a potential for better allocation of overall health care resources. PREVIOUS PUBLICATION: The data applied in this article was originally published in Norwegian in: Børretzen I, Lysdahl KB, Olerud HM: Radiologi i Noreg – undersøkingsfrekvens per 2002, tidstrendar, geografisk variasjon og befolkningsdose. StrålevernRapport 2006:6. Østerås: The Norwegian Radiation Protection Authority. The Norwegian Radiation Protection Authority has given the authors permission to republish the data

IL-17-high asthma with features of a psoriasis immunophenotype

BACKGROUND: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. OBJECTIVE: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. METHODS: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17-high and IL-13-high asthma phenotypes. RESULTS: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17-high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. CONCLUSION: The IL-17-high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-1

Baltic Salmon, Salmo salar, from Swedish River Lule Älv Is More Resistant to Furunculosis Compared to Rainbow Trout

BACKGROUND: Furunculosis, caused by Aeromonas salmonicida, continues to be a major health problem for the growing salmonid aquaculture. Despite effective vaccination programs regular outbreaks occur at the fish farms calling for repeated antibiotic treatment. We hypothesized that a difference in natural susceptibility to this disease might exist between Baltic salmon and the widely used rainbow trout. STUDY DESIGN: A cohabitation challenge model was applied to investigate the relative susceptibility to infection with A. salmonicida in rainbow trout and Baltic salmon. The course of infection was monitored daily over a 30-day period post challenge and the results were summarized in mortality curves. RESULTS: A. salmonicida was recovered from mortalities during the entire test period. At day 30 the survival was 6.2% and 34.0% for rainbow trout and Baltic salmon, respectively. Significant differences in susceptibility to A. salmonicida were demonstrated between the two salmonids and hazard ratio estimation between rainbow trout and Baltic salmon showed a 3.36 higher risk of dying from the infection in the former. CONCLUSION: The finding that Baltic salmon carries a high level of natural resistance to furunculosis might raise new possibilities for salmonid aquaculture in terms of minimizing disease outbreaks and the use of antibiotics

A Synthesis of Tagging Studies Examining the Behaviour and Survival of Anadromous Salmonids in Marine Environments

This paper synthesizes tagging studies to highlight the current state of knowledge concerning the behaviour and survival of anadromous salmonids in the marine environment. Scientific literature was reviewed to quantify the number and type of studies that have investigated behaviour and survival of anadromous forms of Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), brown trout (Salmo trutta), steelhead (Oncorhynchus mykiss), and cutthroat trout (Oncorhynchus clarkii). We examined three categories of tags including electronic (e.g. acoustic, radio, archival), passive (e.g. external marks, Carlin, coded wire, passive integrated transponder [PIT]), and biological (e.g. otolith, genetic, scale, parasites). Based on 207 papers, survival rates and behaviour in marine environments were found to be extremely variable spatially and temporally, with some of the most influential factors being temperature, population, physiological state, and fish size. Salmonids at all life stages were consistently found to swim at an average speed of approximately one body length per second, which likely corresponds with the speed at which transport costs are minimal. We found that there is relatively little research conducted on open-ocean migrating salmonids, and some species (e.g. masu [O. masou] and amago [O. rhodurus]) are underrepresented in the literature. The most common forms of tagging used across life stages were various forms of external tags, coded wire tags, and acoustic tags, however, the majority of studies did not measure tagging/handling effects on the fish, tag loss/failure, or tag detection probabilities when estimating survival. Through the interdisciplinary application of existing and novel technologies, future research examining the behaviour and survival of anadromous salmonids could incorporate important drivers such as oceanography, tagging/handling effects, predation, and physiology

Comparison of participants and non-participants to the ORISCAV-LUX population-based study on cardiovascular risk factors in Luxembourg

BACKGROUND: Poor response is a major concern in public health surveys. In a population-based ORISCAV-LUX study carried out in Grand-Duchy of Luxembourg to assess the cardiovascular risk factors, the non-response rate was not negligible. The aims of the present work were: 1) to investigate the representativeness of study sample to the general population, and 2) to compare the known demographic and cardiovascular health-related profiles of participants and non-participants. METHODS: For sample representativeness, the participants were compared to the source population according to stratification criteria (age, sex and district of residence). Based on complementary information from the "medical administrative database", further analysis was carried out to assess whether the health status affected the response rate. Several demographic and morbidity indicators were used in the univariate comparison between participants and non-participants. RESULTS: Among the 4452 potentially eligible subjects contacted for the study, there were finally 1432 (32.2%) participants. Compared to the source population, no differences were found for gender and district distribution. By contrast, the youngest age group was under-represented while adults and elderly were over-represented in the sample, for both genders. Globally, the investigated clinical profile of the non-participants was similar to that of participants. Hospital admission and cardiovascular health-related medical measures were comparable in both groups even after controlling for age. The participation rate was lower in Portuguese residents as compared to Luxembourgish (OR = 0.58, 95% CI: 0.48-0.69). It was also significantly associated with the professional status (P < 0.0001). Subjects from the working class were less receptive to the study than those from other professional categories. CONCLUSION: The 32.2% participation rate obtained in the ORISCAV-LUX survey represents the realistic achievable rate for this type of multiple-stage, nationwide, population-based surveys. It corresponds to the expected rate upon which the sample size was calculated. Given the absence of discriminating health profiles between participants and non-participants, it can be concluded that the response rate does not invalidate the results and allows generalizing the findings for the population

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10(-6)) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases

Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus

Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae

Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation

Effects of oil and global environmental drivers on two keystone marine invertebrates

Ocean warming (OW) and acidification (OA) are key features of global change and are predicted to have negative consequences for marine species and ecosystems. At a smaller scale increasing oil and gas activities at northern high latitudes could lead to greater risk of petroleum pollution, potentially exacerbating the effects of such global stressors. However, knowledge of combined effects is limited. This study employed a scenario-based, collapsed design to investigate the impact of one local acute stressor (North Sea crude oil) and two chronic global drivers (pH for OA and temperature for OW), alone or in combination on aspects of the biology of larval stages of two key invertebrates: the northern shrimp (Pandalus borealis) and the green sea urchin (Strongylocentrotus droebachiensis). Both local and global drivers had negative effects on survival, development and growth of the larval stages. These effects were species- and stage-dependent. No statistical interactions were observed between local and global drivers and the combined effects of the two drivers were approximately equal to the sum of their separate effects. This study highlights the importance of adjusting regulation associated with oil spill prevention to maximize the resilience of marine organisms to predicted future global conditions