Mental health by gender-specific occupational groups : Profiles, risks and dominance of predictors

Background: We defined gender-specific profiles of mental ill-health for the main occupational groups using three outcomes; antidepressant use, sickness absence (SA) due to depression, and suicides. We also examined which occupational groups had the highest risk of the outcomes, and compared the importance of their predictors. Methods: From a random register cohort of Finnish working age population, individuals in the six largest occupational groups in 2004 for men and women were included (N = 414 357). We used register data to define the first antidepressant purchase (i.e. use), the first long-term SA spell for depression, and suicide between Jan 1st 2005 and Dec 31st 2014. We assessed the risk of each outcome by occupational group with logistic regression models, and used dominance analysis to compare the relative importance of predictors. Results: In all six occupational groups for women, the prevalence of antidepressant use and SA for depression was higher than in the men's occupational groups. The opposite was observed for suicides. The risk of antidepressant use was lower, but the risk of suicide was 2-times higher among men in low vs. high-skilled occupations. Among women, a lower skill-level was associated with a higher risk of SA due to depression. Gender was the most important predictor of all outcomes. Limitations: We lacked information on history of medication use or health problems prior to follow-up. Conclusions: Gendered occupational status was an underlying factor explaining distinctive mental health profiles in the working population. Occupational class-dependent behavioural patterns related to mental health existed among men.Peer reviewe

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

Background and methods Pim family proteins are oncogenic kinases implicated in several types of cancer and involved in regulation of cell proliferation, survival as well as motility. Here we have investigated the ability of Pim kinases to promote metastatic growth of prostate cancer cells in two xenograft models for human prostate cancer. We have also evaluated the efficacy of Pim-selective inhibitors to antagonize these effects. Results We show here that tumorigenic growth of both subcutaneously and orthotopically inoculated prostate cancer xenografts is enhanced by stable overexpression of either Pim-1 or Pim-3. Moreover, Pim-overexpressing orthotopic prostate tumors are highly invasive and able to migrate not only to the nearby prostate-draining lymph nodes, but also into the lungs to form metastases. When the xenografted mice are daily treated with the Pim-selective inhibitor DHPCC-9, both the volumes as well as the metastatic capacity of the tumors are drastically decreased. Interestingly, the Pim-promoted metastatic growth of the orthotopic xenografts is associated with enhanced angiogenesis and lymphangiogenesis. Furthermore, forced Pim expression also increases phosphorylation of the CXCR4 chemokine receptor, which may enable the tumor cells to migrate towards tissues such as the lungs that express the CXCL12 chemokine ligand. Conclusions Our results indicate that Pim overexpression enhances the invasive properties of prostate cancer cells in vivo. These effects can be reduced by the Pim-selective inhibitor DHPCC-9, which can reach tumor tissues without serious side effects. Thus, Pim-targeting therapies with DHPCC-9-like compounds may help to prevent progression of local prostate carcinomas to fatally metastatic malignancies.Peer reviewe

Conditions for forming composite carbon nanotube-diamond like carbon material that retain the good properties of both materials

Peer reviewe

Tricyclic Benzo[cd]azulenes Selectively Inhibit Activities of Pim Kinases and Restrict Growth of Epstein-Barr Virus-Transformed Cells

Peer reviewe

Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia

BACKGROUND: A reliable prediction of the causative agent of community-acquired pneumonia (CAP) is not possible based on clinical features. Our aim was to test, whether the measurement of the expression of complement receptors or Fcγ receptors on neutrophils and monocytes would be a useful preliminary test to differentiate between bacterial and viral pneumonia. METHODS: Sixty-eight patients with CAP were studied prospectively. Thirteen patients had pneumococcal pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia, and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor expression was measured within 2 days of hospital admission. RESULTS: The mean expression of complement receptor 1 (CR1) on neutrophils was significantly higher in the patients with pneumococcal pneumonia than in those with influenza A pneumonia. The mean expression of CR1 was also significantly higher in aetiologically undefined pneumonia than in influenza A pneumonia, but there was no difference between pneumococcal and undefined pneumonia. CONCLUSION: Our results suggest that the expression of CR1 is higher in classical bacterial pneumonia than in viral pneumonia. Determination of the expression of CR1 may be of value as an additional rapid tool in the aetiological diagnosis, bacterial or viral infection, of CAP. These results are preliminary and more research is needed to assess the utility of this new method in the diagnostics of pneumonia

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

Publisher Copyright: © 2022, The Author(s).We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.Peer reviewe

A molecular-based identification resource for the arthropods of Finland

Publisher Copyright: © 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.Peer reviewe

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Funding Information: This research has been conducted using the UK Biobank Resource. This research has been conducted using the Danish National Biobank resource. The authors are grateful to the Raine Study participants and their families, and to the Raine Study research staff for cohort co-ordination and data collection. QIMR is grateful to the twins and their families for their generous participation in these studies. We would like to thank staff at the Queensland Institute of Medical Research: Anjali Henders, Dixie Statham, Lisa Bowdler, Ann Eldridge, and Marlene Grace for sample collection, processing and genotyping, Scott Gordon, Brian McEvoy, Belinda Cornes and Beben Benyamin for data QC and preparation, and David Smyth and Harry Beeby for IT support. HBCS Acknowledgements: We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Juho Vainio Foundation, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. Finrisk study is grateful for the THL DNA laboratory for its skillful work to produce the DNA samples used in this study and thanks the Sanger Institute and FIMM genotyping facilities for genotyping the samples. We thank the MOLGENIS team and Genomics Coordination Center of the University Medical Center Groningen for software development and data management, in particular Marieke Bijlsma and Edith Adriaanse. This work was supported by the Leenards Foundation (to Z.K.), the Swiss National Science Foundation (31003A_169929 to Z.K., Sinergia grant CRSII33-133044 to AR), Simons Foundation (SFARI274424 to AR) and SystemsX.ch (51RTP0_151019 to Z.K.). A.R.W., H.Y. and T.M.F. are supported by the European Research Council grant: 323195:SZ-245. M.A.T., M.N.W. and An.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). For full funding information of all participating cohorts see Supplementary Note 2. Publisher Copyright: © 2017 The Author(s).There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (> 2.4 cm), weight ( 5 kg), and body mass index (BMI) (> 3.5 kg/m(2)). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 x 10(-10), 6.0 x 10(-5), and 2.9 x 10(-3)). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.Peer reviewe

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57