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

Association between suicidal behaviour and impaired glucose metabolism in depressive disorders

Background: Disturbances in lipid metabolism have been linked to suicidal behaviour, but little is known about the association between suicide risk and abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia may increase the risk of depression and also the risk for suicide, we therefore studied associations between suicidal behaviour and disturbances in glucose metabolism in depressive patients who had been referred to depression nurse case managers. Methods: Patients aged 35 years and older (N = 448, mean age 51 years) who were experiencing a new depressive episode, who were referred to depression nurse case managers in 2008-2009 and who scored = 10 on the Beck Depression Inventory were enrolled in this study. The study was conducted in municipalities within the Central Finland Hospital District (catchment area of 274 000 inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose and lipid determinations, were drawn from participants after 12 h of fasting, which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin Sensitivity Check Index (QUICKI) method.' Results: Suicidal ideation (49 %) and previous suicide attempts (16 %) were common in patients with major depressive disorder or dysthymia. Patients with depression and suicidal behaviour had higher blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose levels associated positively with the prevalence of suicidal behaviour, and the linearity was significant at baseline (p for linearity: 0.012, adjusted for age and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age and sex). QUICKI levels associated with suicidal behavior (p for linearity across tertiles of QUICKI: 0.026). Total and LDL cholesterol and triglyceride levels were also higher in those patients with suicidal behaviour. Multivariate analysis revealed that blood glucose levels, BDI scores and antidepressive medications associated with suicidal behaviour. Conclusion: Insulin resistance and disturbances in glucose and lipid metabolism may be more common in middle-aged depressive patients with suicidal behaviour.Peer reviewe

Exposure to Airborne Particles and Volatile Organic Compounds from Polyurethane Molding, Spray Painting, Lacquering, and Gluing in a Workshop

Due to the health risk related to occupational air pollution exposure, we assessed concentrations and identified sources of particles and volatile organic compounds (VOCs) in a handcraft workshop producing fishing lures. The work processes in the site included polyurethane molding, spray painting, lacquering, and gluing. We measured total VOC (TVOC) concentrations and particle size distributions at three locations representing the various phases of the manufacturing and assembly process. The mean working-hour TVOC concentrations in three locations studied were 41, 37, and 24 ppm according to photo-ionization detector measurements. The mean working-hour particle number concentration varied between locations from 3000 to 36,000 cm(-3). Analysis of temporal and spatial variations of TVOC concentrations revealed that there were at least four substantial VOC sources: spray gluing, mold-release agent spraying, continuous evaporation from various lacquer and paint containers, and either spray painting or lacquering (probably both). The mold-release agent spray was indirectly also a major source of ultrafine particles. The workers' exposure can be reduced by improving the local exhaust ventilation at the known sources and by increasing the ventilation rate in the area with the continuous source.Peer reviewe

Effects of physicochemical properties of TiO2 nanomaterials for pulmonary inflammation, acute phase response and alveolar proteinosis in intratracheally exposed mice

Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.Peer reviewe

The effect of improvisational music therapy on the treatment of depression: protocol for a randomised controlled trial

Background. Music therapy is frequently offered to individuals suffering from depression. Despite the lack of research into the effects of music therapy on this population, anecdotal evidence suggests that the results are rather promising. The aim of this study is to examine whether improvisational, psychodynamically orientated music therapy in an individual setting helps reduce symptoms of depression and improve other health-related outcomes. In particular, attention will be given to mediator agents, such as musical expression and interaction in the sessions, as well as to the explanatory potential of EEG recordings in investigating emotion related music perception of individuals with depression. Methods. 85 adults (18–50 years of age) with depression (ICD-10: F 32 or F33) will be randomly assigned to an experimental or a control condition. All participants will receive standard care, but the experimental group will be offered biweekly sessions of improvisational music therapy over a period of 3 months. A blind assessor will measure outcomes before testing, after 3 months, and after 6 months. Discussion. This study aims to fill a gap in knowledge as to whether active (improvisational) music therapy applied to people with depression improves their condition. For the first time in this context, the mediating processes, such as changes in musical expression and interaction during the course of therapy, will be objectively investigated, and it is expected that the results will provide new insights into these processes. Furthermore, the findings are expected to reveal whether music related emotional experiences, as measured by EEG, can be utilized in assessing a depressive client's improvement in the therapy. The size and the comprehensiveness of the study are sufficient for generalizing its findings to clinical practice as well as to further music therapy research. Trial registration. ISRCTN84185937peerReviewe

Varastotestien ja vähittäiskaupan porkkana-aineisto

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Improvisaatiopohjainen yksilömusiikkiterapia masennuksen hoidossa : kontrolloitu, satunnainen tutkimus

Masennus on yleinen sairaus, joka vaikuttaa ihmisen elämään laaja-alaisesti, heikentäen muun muassa yksilön sosiaalisia taitoja ja vaikeuttaen kykyä tunnistaa ja ilmaista tunteita. Masennukseen liitetään myös vaikeudet ilmaista ja säädellä negatiivisia tunteita kuten vihaa. Tässä tutkimuksessa selvitettiin kliiniseen improvisaatioon perustuvan lyhytkestoisen musiikkiterapia-intervention lisäarvoa Käypä hoidon mukaiseen masennuksen hoitoon (engl. standard care, jatkossa Se) lisättynä verrattuna pelkkään se hoitoon. Psykiatriset arviot toteutettiin sekä koe- että kontrolliryhmille lähtötilanteessa ennen satunnaistamista, sekä kolmen kuukauden (musiikkiterapiaintervention jälkeen) ja kuuden kuukauden kuluttua uudestaan. Tutkimus osoitti, että musiikkiterapian ja se:n yhdistelmä vähensi masennus- ja ahdistusoireita sekä paransi yleistä toimintakykyä merkittävästi enemmän kuin pelkkä se.peerReviewe