Repeated simultaneous cortical electrophysiological and behavioral recording in rats exposed to manganese-containing nanoparticles

Male Wistar rats wearing chronically implanted cortical electrodes were exposed to Mn-containing nanoparticles via the airways for 8 weeks following a 2-week pre-exposure period. The rats’ cortical electrical activity and open field motility was recorded simultaneously, in weekly repetitions. It was supposed that this technique can provide better insight in the development of Mn-induced CNS damage. Decreased motility (less distance covered, longer periods of immobility) and increased total power of cortical electrical activity developed in parallel in the first 4–5 weeks of treatment but showed little change afterwards. Both the behavioral and the electrophysiological effect were in fair correlation with the rats’ internal Mn exposure determined from brain samples. The results confirmed the non-linear dose- and time-dependence of Mn effects suggested by previous studies. Repeated simultaneous behavioral and electrophysiological recording during a longer treatment with neurotoxic metals (or other xenobiotics) seems to be a promising method

Novel association between plasma matrix metalloproteinase-9 and risk of incident atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in Communities Study

Background: Previous cross-sectional studies have suggested that biomarkers of extracellular matrix remodelling are associated with atrial fibrillation (AF), but no prospective data have yet been published. Hence, we examine whether plasma matrix metalloproteinases (MMP) and their inhibitors are related to increased risk of incident AF.Methods: We used a case-cohort design in the context of the prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible men and women free from AF in 1990-92, we selected a stratified random sample of 500 individuals without and 580 with incident AF over a mean follow-up of 11.8 years. Using a weighted proportional hazards regression model, the relationships between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were examined after adjusting for confounders.Results: In models adjusted for age, sex and race, all biomarkers were associated with AF, but only the relationship between plasma MMP-9 remained significant in the fully-adjusted model: each one standard deviation increase in MMP-9 was associated with 27% (95% Confidence Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction with race or sex. Individuals with above mean levels of MMP-9 were more likely to be male, white and current smokers.Conclusions: The findings suggest that elevated levels of MMP-9 are independently associated with increased risk of AF. However, given the lack of specificity of MMP-9 to atrial tissue, it remains to be determined whether the observed relationship reflects the impact of atrial fibrosis or more generalized fibrosis on risk of incident AF

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology