Burden of cardiovascular diseases and depression attributable to psychosocial work exposures in 28 European countries.

BACKGROUND: This study aimed to estimate the annual burden of cardiovascular diseases and depression attributable to five psychosocial work exposures in 28 European Union countries (EU28) in 2015. METHODS: Based on available attributable fraction estimates, the study covered five exposures, job strain, effort-reward imbalance, job insecurity, long working hours and workplace bullying; and five outcomes, coronary/ischemic heart diseases (CHD), stroke, atrial fibrillation, peripheral artery disease and depression. We estimated the burden attributable to each exposure separately and all exposures together. We calculated Disability-Adjusted Life Years (DALY) rate per 100 000 workers in each country for each outcome attributable to each exposure and tested the differences between countries and between genders using the Wald test. RESULTS: The overall burden of CHD attributable to the five studied psychosocial work exposures together was estimated at 173 629 DALYs for men and 39 238 for women, 5092 deaths for men and 1098 for women in EU28 in 2015. The overall burden of depression was estimated at 528 549 DALYs for men and 344 151 for women (respectively 7862 and 1823 deaths). The three highest burdens in DALYs in EU28 in 2015 were found for depression attributable to job strain (546 502 DALYs), job insecurity (294 680 DALYs) and workplace bullying (276 337 DALYs). Significant differences between countries were observed for DALY rates per 100 000 workers. CONCLUSIONS: Such results are necessary as decision tools for decision-makers (governments, employers and trade unions) when defining public health priorities and work stress preventive strategies in Europe.

Issue with Evaluating Costs Over Time in a Context of Medical Guideline Changes: An Example in Myocardial Infarction Care Based on a Longitudinal Study from 1997 to 2018.

BACKGROUND: Cost studies appear sporadically in the scientific literature and are rarely revised unless drastic technological advancements occur. However, health technologies and medical guidelines evolve over time. It is unclear if these changes render obsolete prior estimates. We examined this issue in a cost study in the context of patients' first myocardial infarction (MI), a clinical area prone to such continuous evolution in care. METHODS: We conducted a longitudinal cost analysis based on a Quebec cohort. Quebec health administrative databases were used to identify incident MI cases using diagnostic codes from the international classification of diseases (ICD-9 and ICD-10). Physician fees and hospitalization costs (ie, costs incurred by the hospital center) were derived from administrative databases and a university hospital's finance department. All costs were converted to 2019 Canadian dollars. Nonparametric bootstraps were used to estimate 95% confidence intervals (CI) of the average costs of an episode of care. Generalized linear regressions were used to examine temporal trends of cost. RESULTS: Our study sample consists of 261 patients hospitalized for a first MI. The average total cost for this first event was estimated at $5782 (95% CI: $5293 - $6373). Though total costs remained stable over time, physician fees increased by 123% ($1240 vs $2761) whereas total hospital length of stay dropped by 17% (6.6 vs 5.5 days) over the 21-year period. CONCLUSION: Patients' first MI hospitalization impose an economic burden on the healthcare system. Though overall costs remained stable, our results suggest that some cost components varied over time.

MAP1a associated light chain 3 increases microtubule stability by suppressing microtubule dynamics.

Microtubule associated proteins (MAP) have been shown to play a role in microtubule stability in axons and dendrites, in determining neuronal shape and in regulating the balance between rigidity and plasticity in neuronal processes. MAP1a is the most abundant MAP in the adult brain, localized in axons and dendrites of neurons. MAP1a associates with three light chain molecules (LC1, LC2, LC3) that have been shown to bind microtubules independent of heavy chain molecules. In the present study we investigate the role of MAP1a associated light chain molecules in stabilizing microtubules and altering microtubule dynamics in vivo. All three light chain molecules co-localized with microtubules by fluorescence microscopy and bound taxol stabilized microtubules in an in vitro binding assay. LC-microtubule binding was associated with increased microtubule stability as shown by co localization of LC molecules with detyrosinated microtubules and increased amounts of detyrosinated tubulin in whole cell extracts. Both LC1 and LC2 binding to microtubules reorganized microtubules into wavy bundles that were resistant to nocodazole induced drug depolymerization. In contrast, LC3 bound microtubules were not resistant to nocodazole and the microtubule network of LC3 expressing cells was similar to media controls. Although LC3 bound microtubules were not resistant to drug induced depolymerization, in vivo measurement of microtubule dynamics shows that LC3 stabilizes microtubule networks by decreasing microtubule dynamicity and promoting growth over shortening events.

Functional characterization of artemin, a ferritin homolog synthesized in Artemia embryos during encystment and diapause.

Oviparously developing embryos of the crustacean Artemia franciscana encyst and enter diapause, exhibiting a level of stress tolerance seldom seen in metazoans. The extraordinary stress resistance of encysted Artemia embryos is thought to depend in part on the regulated synthesis of artemin, a ferritin superfamily member. The objective of this study was to better understand artemin function, and to this end the protein was synthesized in Escherichia coli and purified to apparent homogeneity. Purified artemin consisted of oligomers approximately 700 kDa in molecular mass that dissociated into monomers and a small number of dimers upon SDS/PAGE. Artemin inhibited heat-induced aggregation of citrate synthase in vitro, an activity characteristic of molecular chaperones and shown here to be shared by apoferritin and ferritin. This is the first report that apoferritin/ferritin may protect cells from stress other than by iron sequestration. Stably transfected mammalian cells synthesizing artemin were more resistant to heat and H(2)O(2) than were cells transfected with vector only, actions also shared by molecular chaperones such as the small heat shock proteins. The data indicate that artemin is a structurally modified ferritin arising either from a common ancestor gene or by duplication of the ferritin gene. Divergence, including acquisition of a C-terminal peptide extension and ferroxidase center modification, eliminated iron sequestration, but chaperone activity was retained. Therefore, because artemin accumulates abundantly during development, it has the potential to protect embryos from stress during encystment and diapause without adversely affecting iron metabolism.

Inhibition of apoptosis by p26: implications for small heat shock protein function during Artemia development.

p26, an abundantly expressed small heat shock protein, is thought to establish stress resistance in oviparously developing embryos of the crustacean Artemia franciscana by preventing irreversible protein denaturation, but it might also promote survival by inhibiting apoptosis. To test this possibility, stably transfected mammalian cells producing p26 were generated and their ability to resist apoptosis induction determined. Examination of immunofluorescently stained transfected 293H cells by confocal microscopy demonstrated p26 is diffusely distributed in the cytoplasm with a minor amount of the protein in nuclei. As shown by immunoprobing of Western blots, p26 constituted approximately 0.6% of soluble cell protein. p26 localization and quantity were unchanged during prolonged culture, and the protein had no apparent ill effects on transfected cells. Molecular sieve chromatography in Sepharose 6B revealed p26 oligomers of about 20 monomers, with a second fraction occurring as larger aggregates. A similar pattern was observed in sucrose gradients, but overall oligomer size was smaller. Mammalian cells containing p26 were more thermotolerant than cells transfected with the expression vector only, and as measured by annexin V labeling, Hoescht 33342 nuclear staining and procaspase-3 activation, transfected cells effectively resisted apoptosis induction by heat and staurosporine. The ability to confer thermotolerance and limit heat-induced apoptosis is important because Artemia embryos are frequently exposed to high temperature in their natural habitat. p26 also blocked apoptosis in transfected cells during drying and rehydration, findings with direct relevance to Artemia life history characteristics because desiccation terminates cyst diapause. Thus, in addition to functioning as a molecular chaperone, p26 inhibits apoptosis, an activity shared by other small heat shock proteins and with the potential to play an important role during Artemia embryo development.

A small stress protein acts synergistically with trehalose to confer desiccation tolerance on mammalian cells.

The ability to desiccate mammalian cells while maintaining a high degree of viability would be very important in many areas of biological science, including tissue engineering, cell transplantation, and biosensor technologies. Certain proteins and sugars found in animals capable of surviving desiccation might aid this process. We report here that human embryonic kidney (293H) cells transfected with the gene for the stress protein p26 from Artemia and loaded with trehalose showed a sharp increase in survival during air-drying. Further, we find vacuum-drying greatly improved the ability of the cells to survive, and that the physical shape and structure of the cellular sample had a large influence on recovery following rehydration. Cells suspended in a rounded droplet survived desiccation markedly better than those spread as a thin film. Finally, we used alamarBlue to monitor cellular metabolism and Hema 3 to assess colony formation after vacuum-drying. AlamarBlue fluorescence indicated that the transfected 293H cells expressing p26 (E11'L) grew much better than the control 293H cells. In fact, immediate survival and colony formation in E11'L cells increased as much as 34-fold compared with control cells when the samples were dried to a water content of 0.2 g H2O/g dry weight, as measured by gravimetric analysis. These results indicate that p26 improves cell survival following drying and rehydration, and suggest that dry storage of mammalian cells is a likely possibility in the future.