Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs

In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- and hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed

Developing a company-specific job exposure matrix for the Asbest Chrysotile Cohort Study

OBJECTIVES: Exposure assessment for retrospective industrial cohorts are often hampered by limited availability of historical measurements. This study describes the development of company-specific job-exposure matrices (JEMs) based on measurements collected over five decades for a cohort study of 35 837 workers (Asbest Chrysotile Cohort Study) in the Russian Federation to estimate their cumulative exposure to chrysotile containing dust and fibres. METHODS: Almost 100 000 recorded stationary dust measurements were available from 1951-2001 (factories) and 1964-2001 (mine). Linear mixed models were used to extrapolate for years where measurements were not available or missing. Fibre concentrations were estimated using conversion factors based on side-by-side comparisons. Dust and fibre JEMs were developed and exposures were allocated by linking them to individual workers' detailed occupational histories. RESULTS: The cohort covered a total of 515 355 employment-years from 1930 to 2010. Of these individuals, 15% worked in jobs not considered professionally exposed to chrysotile. The median cumulative dust exposure was 26 mg/m3 years for the entire cohort and 37.2 mg/m3 years for those professionally exposed. Median cumulative fibre exposure was 16.4 fibre/cm3 years for the entire cohort and 23.4 fibre/cm3 years for those professionally exposed. Cumulative exposure was highly dependent on birth cohort and gender. Of those professionally exposed, women had higher cumulative exposures than men as they were more often employed in factories with higher exposure concentrations rather than in the mine. CONCLUSIONS: Unique company-specific JEMs were derived using a rich measurement database that overlapped with most employment-years of cohort members and will enable estimation of quantitative exposure-response

Soluble Cyanobacterial Carotenoprotein as a Robust Antioxidant Nanocarrier and Delivery Module

To counteract oxidative stress, antioxidants including carotenoids are highly promising, yet their exploitation is drastically limited by the poor bioavailability and fast photodestruction, whereas current delivery systems are far from being efficient. Here we demonstrate that the recently discovered nanometer-sized water-soluble carotenoprotein from Anabaena sp. PCC 7120 (termed AnaCTDH) transiently interacts with liposomes to efficiently extract carotenoids via carotenoid-mediated homodimerization, yielding violet–purple protein samples. We characterize the spectroscopic properties of the obtained pigment–protein complexes and the thermodynamics of liposome–protein carotenoid transfer and demonstrate the delivery of carotenoid echinenone from AnaCTDH into liposomes with an efficiency of up to 70 ± 3%. Most importantly, we show efficient carotenoid delivery to membranes of mammalian cells, which provides protection from reactive oxygen species (ROS). Incubation of neuroblastoma cell line Tet21N in the presence of 1 μM AnaCTDH binding echinenone decreased antimycin A ROS production by 25% (p < 0.05). The described carotenoprotein may be considered as part of modular systems for the targeted antioxidant delivery.BMBF, 01DJ15007, Carotenoidbindende photoschaltbare Proteine: Lichtinduzierte Dynamik und Anwendungen in modernen mikroskopischen Verfahre

Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the chernobyl accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy-1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy-1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy-1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p= 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment

Is adjustment for smoking needed in a cohort study of cancer mortality among chrysotile asbestos factory and mine workers?

Introduction A retrospective cohort study of 35 840 employees is currently being conducted in a chrysotile mine and its processing facilities in Asbest, the Russian Federation. The primary aim is to quantify exposure-response relationships for cancers potentially associated with chrysotile exposure. Some of those cancers are also tobacco-related; however individual-level information on tobacco use is not available for the full cohort. To address this gap, a cross-sectional study of current and retired workers from JSC Uralasbest was conducted to assess the relationship between smoking status and workers' exposure to chrysotile. Methods Self-administered questionnaires were completed by current workers during meetings organized by occupational safety specialists. Retired workers filled in questionnaires during Veterans' meetings or were interviewed via telephone or at home. Estimates of exposure to chrysotile were available for 999 current and 3795 retired workers who were linked to the cohort study. Results Among the 7451 respondents (n=3698 men and n=3753 women), 66% of men and 9% of women were ever-smokers. Smoking prevalence was stable across birth decades in men, but increased fro

Is adjustment for smoking needed in a cohort study of cancer mortality among chrysotile asbestos factory and mine workers?

Introduction A retrospective cohort study of 35 840 employees is currently being conducted in a chrysotile mine and its processing facilities in Asbest, the Russian Federation. The primary aim is to quantify exposure-response relationships for cancers potentially associated with chrysotile exposure. Some of those cancers are also tobacco-related; however individual-level information on tobacco use is not available for the full cohort. To address this gap, a cross-sectional study of current and retired workers from JSC Uralasbest was conducted to assess the relationship between smoking status and workers' exposure to chrysotile. Methods Self-administered questionnaires were completed by current workers during meetings organized by occupational safety specialists. Retired workers filled in questionnaires during Veterans' meetings or were interviewed via telephone or at home. Estimates of exposure to chrysotile were available for 999 current and 3795 retired workers who were linked to the cohort study. Results Among the 7451 respondents (n=3698 men and n=3753 women), 66% of men and 9% of women were ever-smokers. Smoking prevalence was stable across birth decades in men, but increased fro

Tobacco smoking among chrysotile asbestos workers in Asbest in the Russian Federation

Objectives A historical cohort study of cancer mortality is being conducted among workers in a chrysotile mine and its enrichment factories in the town of Asbest, Russian Federation. Because individual-level information on tobacco use is not available for Asbest Chrysotile Cohort members, a cross-sectional survey of smoking behaviours was conducted among active and retired workers. Methods Self-administered questionnaires were completed by active workers during meetings organised by occupational safety personnel. Retired workers completed questionnaires during meetings of the Veterans Council or were interviewed via telephone or in person. Of the respondents, 46% could be linked to the Asbest Chrysotile Cohort. Among those, logistic regression models were used to assess associations between smoking and cumulative dust exposure. Results Among men, smoking prevalence was high and relatively consistent across birth decades (average, 66%), and was similar in workers across all levels of cumulative dust exposure (p trend, 0.44). Among women, the prevalence increased fro

Tobacco smoking among chrysotile asbestos workers in Asbest in the Russian Federation

Objectives A historical cohort study of cancer mortality is being conducted among workers in a chrysotile mine and its enrichment factories in the town of Asbest, Russian Federation. Because individual-level information on tobacco use is not available for Asbest Chrysotile Cohort members, a cross-sectional survey of smoking behaviours was conducted among active and retired workers. Methods Self-administered questionnaires were completed by active workers during meetings organised by occupational safety personnel. Retired workers completed questionnaires during meetings of the Veterans Council or were interviewed via telephone or in person. Of the respondents, 46% could be linked to the Asbest Chrysotile Cohort. Among those, logistic regression models were used to assess associations between smoking and cumulative dust exposure. Results Among men, smoking prevalence was high and relatively consistent across birth decades (average, 66%), and was similar in workers across all levels of cumulative dust exposure (p trend, 0.44). Among women, the prevalence increased fro