132 research outputs found

    Antidepressant use and work-related injuries

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    Background. Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. Method. Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). Results. In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin re-uptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). Conclusions. Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury.Peer reviewe

    Enrichment and sequencing of phosphopeptides on indium tin oxide coated glass slides

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    Unambiguous identification of phosphorylation sites is of premier importance to biologists, who seek to understand the role of phosphorylation from the perspective of site-specific control of biological phenomena. Despite this widely asked and highly specific information, many methods developed are aimed at analysis of complete proteomes, indeed even phospho-proteomes, surpassing the basic requests of many biologists. We have therefore further developed a simple method that specifically deals with the analysis of multiple phosphorylation sites on singular proteins or small collections of proteins. With this method, the whole purification process, from sample application to MALDI-MS analysis, can be performed on commercially available indium tin oxide (ITO) coated glass slides. We show that fifteen (15) samples can be purified within one hour, and that low femtomole sensitivity can be achieved. This limit of identification is demonstrated by the successful MS/MS-based identification of 6 fmol of monophosphopeptide from beta-casein. We demonstrate that the method can be applied for identifying phosphorylation sites from recombinant and cell-derived biological protein samples. Since ITO-coated glass slides are inexpensive and available from several suppliers the method is readily and inexpensively available to other researchers. Taken together, the presented protocols and materials render this method as an extremely fast and sensitive phosphopeptide identification protocol that should aid biologists in discovery and validation of phosphorylation sites

    HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma

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    Background: A key feature of clear cell renal cell carcinoma (ccRCC) is the inactivation of the von Hippel-Lindau tumour suppressor protein (pVHL) that leads to the activation of hypoxia-inducible factor (HIF) pathway also in well-oxygenated conditions. Important regulator of HIF-a, prolyl hydroxylase PHD3, is expressed in high amounts in ccRCC. Although several functions and downstream targets for PHD3 in cancer have been suggested, the role of elevated PHD3 expression in ccRCC is not clear.Methods: To gain insight into the functions of high PHD3 expression in ccRCC, we used PHD3 knockdown by siRNA in 786-O cells under normoxic and hypoxic conditions and performed discovery mass spectrometry (LC-MS/MS) of the purified peptide samples. The LC-MS/MS results were analysed by label- free quantification of proteome data using a peptide-level expression-change averaging procedure and subsequent gene ontology enrichment analysis.Results: Our data reveals an intriguingly widespread effect of PHD3 knockdown with 91 significantly regulated proteins. Under hypoxia, the response to PHD3 silencing was wider than under normoxia illustrated by both the number of regulated proteins and by the range of protein expression levels. The main cellular functions regulated by PHD3 expression were glucose metabolism, protein translation and messenger RNA (mRNA) processing. PHD3 silencing led to downregulation of most glycolytic enzymes from glucose transport to lactate production supported by the reduction in extracellular acidification and lactate production and increase in cellular oxygen consumption rate. Moreover, upregulation of mRNA processing-related proteins and alteration in a number of ribosomal proteins was seen as a response to PHD3 silencing. Further studies on upstream effectors of the translational machinery revealed a possible role for PHD3 in regulation of mTOR pathway signalling.Conclusions: Our findings suggest crucial involvement of PHD3 in the maintenance of key cellular functions including glycolysis and protein synthesis in ccRCC

    Within-individual analysis of pain and sickness absence among employees from low and high occupational classes: a record linkage study

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    Objectives Pain is linked to an increased risk of sickness absence (SA); however, the extent to which unmeasured time-invariant differences explain this association is yet unknown. Therefore, we determined the within-individual associations between pain and short-term (in the survey year) and long-term (2 years following the survey years) SA risk in high and low occupational classes while controlling for the potential bias due to unobservable time-invariant characteristics. Methods The Helsinki Health Study data consisting of midlife public sector employees with mailed surveys from up to four time points, and SA record linkage were used (3983 persons). The within-individual estimates were calculated using hybrid negative binomial regression models. Results Acute/subacute pain was associated with a 13% increase in the rate of short-term SA days (incidence rate ratio 1.13 [95% CI 1.01 to 1.27]), while the association was somewhat stronger for chronic pain (1.32 [1.19–1.47]). For the employees in the low occupational class, these associations were robust (1.29 [1.10–1.50] for acute/subacute and 1.43 [1.23–1.66] for chronic pain), whereas only chronic pain was associated with SA among those in the high occupational class (1.25 [1.08–1.46]). Chronic pain was also associated with SA days in the long term without occupational class differences. Similar results were obtained for multisite pain (pain in several locations). Conclusions These results indicate that particularly chronic and multisite pain have a within-individual link to SA but ignoring unobservable differences between those reporting pain and those not might yield overstated effect sizes. Pain might have a different relation to SA in low and high occupational classes.TL and AH are supported by the Academy of Finland (Grants #287488 and #319200). AK is supported by the Economic and Social Research Council (ESRC) (grant ES/L007509/1). OR is supported by the Academy of Finland (grant 1294514) and the Juho Vainio Foundation. OP is supported by the Academy of Finland (grant 1294514). MM is supported by the Finnish Work Environment Fund (grant 115182) and the Juho Vainio Foundation. PB is supported by a Future Fellowship from the Australian Research Council (FT13101444)

    Managing risks to drivers in road transport

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    This report presents a number of case studies in managing risks to road transport drivers. The cases feature a variety of initiatives and interventions to protect drivers.In the road transport sector, as with any other, it is important to pay attention to working conditions in order to ensure a skilled and motivated workforce. Certain characteristics of the sector make it more difficult to practice risk management than in other sectors. But by taking account of how the sector operates in practice, and the characteristics of drivers themselves and the way they work, risks can be successfully manage
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