Innate Immunity and the Pathogenicity of Inhaled Microbial Particles

Non-infectious inhaled microbial particles can cause illness by triggering an inappropriate immunological response. From the pathogenic point of view these illnesses can be seen to be related to on one hand autoimmune diseases and on the other infectious diseases

Stated preferences

Numerous articles dealing with stated preferences are published every year in journals related to agriculture, environment or health. Hence, it is not easy to find all the relevant articles when performing a benefit transfer, a meta-analysis or a review of literature. Also, it is not easy to identify trends or common practices in these fields regarding the elicitation method. We have constructed and made available a unique database comprising 1,657 choice experiment and/or contingent valuation articles published in journals related to agriculture, environment or health between 2004 and 2016. We show that the number of choice experiment studies keeps increasing and the single-bounded dichotomous choice format is the most employed question format in contingent valuation studies. We also consider the new nomenclature proposed by Carson and Louviere (2011) and we show that the “discrete choice experiment” is more popular than the “matching method”, especially in journals related to agriculture

CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure

BackgroundDeletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.MethodsWe studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.ResultsWe were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (>1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure ( 0.5 million f/g) (51.4% vs 16.7%; p=0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p=0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.ConclusionsWe found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.Peer reviewe

CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure

BackgroundDeletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.MethodsWe studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.ResultsWe were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (>1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure ( 0.5 million f/g) (51.4% vs 16.7%; p=0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p=0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.ConclusionsWe found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.Peer reviewe

Long-term changes in the acid and salt concentrations of the Greenland Ice Core Project ice core from electrical stratigraphy

Continuous electrical records covering a climatic cycle are presented for the Greenland Ice Core Project deep ice core from Greenland. Electrical conductivity measurement (ECM) measures the acid content of the ice, and the dielectric profile (DEP) responds to acid, ammonium, and chloride. All features seen can be explained by chemical changes in the ice, and there is no evidence so far for any major change in electrical response with depth or age of the ice. Both records are dominated by the acidity of the ice which varies strongly from acidic in warm periods to alkaline in cold periods, controlled by neutralization by alkaline dust (calcareous and other mineral dust). When Ca is low, the acidity (mainly nitric acid) has a fairly constant background level throughout the cycle, with slightly lower values in ice believed to be from the last interglacial. Ca has to rise only slightly to neutralize the available acidity, so that acidity is a highly nonlinear reflection of climate changes. If neutralization occurred in the aerosol (rather than in the ice), then the number of cloud condensation nuclei over parts of the northern hemisphere could have been reduced, leading to reduced cloud albedo. This nonlinear feedback may have some importance for modeling of climate change. When both acid and ammonium levels are low, the DEP signal can be used to give a rapid indication of chloride trends

Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model

<p>Abstract</p> <p>Background</p> <p>Nanotechnology and engineered nanomaterials (ENM) are here to stay. Recent evidence suggests that exposure to environmental particulate matter exacerbates symptoms of asthma. In the present study we investigated the modulatory effects of titanium dioxide particle exposure in an experimental allergic asthma.</p> <p>Methods</p> <p>Nonallergic (healthy) and ovalbumin-sensitized (asthmatic) mice were exposed via inhalation to two different sizes of titanium dioxide particles, nanosized (nTiO₂) and fine (fTiO₂), for 2 hours a day, three days a week, for four weeks at a concentration of 10 mg/m³. Different endpoints were analysed to evaluate the immunological status of the mice.</p> <p>Results</p> <p>Healthy mice elicited pulmonary neutrophilia accompanied by significantly increased chemokine CXCL5 expression when exposed to nTiO₂. Surprisingly, allergic pulmonary inflammation was dramatically suppressed in asthmatic mice which were exposed to nTiO₂or fTiO₂particles - i.e. the levels of leucocytes, cytokines, chemokines and antibodies characteristic to allergic asthma were substantially decreased.</p> <p>Conclusions</p> <p>Our results suggest that repeated airway exposure to TiO₂particles modulates the airway inflammation depending on the immunological status of the exposed mice.</p

CD8+T Cell Migration to the Skin Requires CD4+Help in a Murine Model of Contact Hypersensitivity

Peer reviewe

Hot spot mutations in Finnish non-small cell lung cancers

Objectives: Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. Materials and methods: Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). Results: Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PlIC3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. Conclusion: Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe