Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships.

OBJECTIVES: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. METHODS: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. RESULTS: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. CONCLUSION: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Dual system of water safety plan auditing in Hungary: benefits and lessons learnt.

A risk-based approach is recognised worldwide as the most reliable means for the provision of safe drinking water. Efficient implementation of the water safety plan (WSP) approach, recommended by the World Health Organization (WHO), is facilitated by an auditing framework. In Hungary, development of WSPs is a legal obligation for water suppliers. WSPs are subject to a two-stage regulatory audit, a consultative central technical audit and a formal local audit. In 2019, a survey was conducted in cooperation with WHO to evaluate audit experiences of over 1,200 WSPs. Recommendations from the central audit significantly improved coherence and compliance of WSPs, confirming the efficiency of the dual approach. The use of a WSP template provided by the national authority further increased consistency and reduced time and work demand of the audit. Both water suppliers and public health authorities indicated a need for further capacity building on WSP development and auditing. The main challenge for water suppliers is the identification and risk assessment of hazards associated with the water source and distribution within premises. The recast European Union drinking water regulation is expected to accelerate the uptake of WSP and strengthen linkages to water catchment management and water safety in buildings.

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer's disease, Parkinson's disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood-brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population.

Wastewater-based modeling, reconstruction, and prediction for COVID-19 outbreaks in Hungary caused by highly immune evasive variants.

(MOTIVATION): Wastewater-based epidemiology (WBE) has emerged as a promising approach for monitoring the COVID-19 pandemic, since the measurement process is cost-effective and is exposed to fewer potential errors compared to other indicators like hospitalization data or the number of detected cases. Consequently, WBE was gradually becoming a key tool for epidemic surveillance and often the most reliable data source, as the intensity of clinical testing for COVID-19 drastically decreased by the third year of the pandemic. Recent results suggests that the model-based fusion of wastewater measurements with clinical data and other indicators is essential in future epidemic surveillance. (METHOD): In this work, we developed a wastewater-based compartmental epidemic model with a two-phase vaccination dynamics and immune evasion. We proposed a multi-step optimization-based data assimilation method for epidemic state reconstruction, parameter estimation, and prediction. The computations make use of the measured viral load in wastewater, the available clinical data (hospital occupancy, delivered vaccine doses, and deaths), the stringency index of the official social distancing rules, and other measures. The current state assessment and the estimation of the current transmission rate and immunity loss allow a plausible prediction of the future progression of the pandemic. (RESULTS): Qualitative and quantitative evaluations revealed that the contribution of wastewater data in our computational epidemiological framework makes predictions more reliable. Predictions suggest that at least half of the Hungarian population has lost immunity during the epidemic outbreak caused by the BA.1 and BA.2 subvariants of Omicron in the first half of 2022. We obtained a similar result for the outbreaks caused by the subvariant BA.5 in the second half of 2022. (APPLICABILITY): The proposed approach has been used to support COVID management in Hungary and could be customized for other countries as well.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

OBJECTIVE: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

SARS-CoV-2 variant detection from wastewater: rapid spread of B.1.1.7 lineage in Hungary.

Wastewater-based epidemiology (WBE) is a recognised tool for tracking community transmission of COVID-19. From the second half of 2020, the emergence of new, highly infective, more pathogenic or vaccine-escape SARS-CoV-2 variants is the major public health concern. Variant analysis in sewage might assist the early detection of new mutations. Weekly raw sewage samples from 22 wastewater treatment plants (WWTPs) in Hungary (representing 40% of the population) were analysed between December 2020 and March 2021 for signature mutations N501Y and del H69/V70 of B.1.1.7 lineage by melting point genotyping and RT-digital droplet PCR (RT-ddPCR). The latter method proved to be more efficient in parallel detection of different variants and also provides quantitative information. Wastewater surveillance indicated that the B.1.1.7 variant first emerged in Budapest in early January 2021 and rapidly became dominant in the entire country. Results are in close agreement with the available clinical data (Pearson's correlation coefficient, R = 0.9153). RT-ddPCR was confirmed to be a reliable tool for tracking emerging variant ratios in wastewaters. It is a rapid and cost-effective method compared to whole-genome sequencing, but only applicable for the detection of known mutations. Efficient variant surveillance might require the combination of multiple methods.

Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Lung Cancer Risk: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project. METHODS: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI). RESULTS: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP µg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk. CONCLUSIONS: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens. IMPACT: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures.

Investigation of the association between lithium levels in drinking water and suicide mortality in Hungary.

BACKGROUND: In recent decades, a series of ecological studies from various countries have attempted to reveal whether there is an association between trace amounts of lithium in drinking water and suicide mortality. With some notable exceptions, results have indicated that there is an inverse association between these two variables. Since Hungary had extremely high rates of suicide with a persistent spatial pattern, we consider that our country is ideal to investigate this research question. METHODS: We carried out our research on Hungarian data at the level of districts (n = 197). The dependent variable was the age- and gender-standardized mortality ratio for suicide (sSMR). Our main explanatory variable was the tap water lithium level (Li) from public drinking water supply systems using their own water source (n = 1 325). Those data, which give full national coverage, were aggregated to the level of districts. Confounding factors were religiosity, alcohol consumption and income. Various regression models were used for statistical calculations. RESULTS: Findings from our most appropriate regression model - adjusted for relevant confounding variables and able to handle spatial autocorrelation and heteroscedasticity - suggest a significant (p < 0.05) and a trend-like (p < 0.1) negative association between Li and sSMR in the total population and among males, respectively. However, such an association was not found between these two variables among females. CONCLUSION: In line with the majority of findings from other countries, our results indicate that the intake of lithium with drinking water may have a gender-dependent suicide-protective effect.

Ahead of the second wave: Early warning for COVID-19 by wastewater surveillance in Hungary.

Wastewater based epidemiology is a potential early warning tool for the detection of COVID-19 outbreak. Sewage surveillance for SARS-CoV-2 RNA was introduced in Hungary after the successful containment of the first wave of the pandemic to forecast the resurge of infections. Three wastewater treatment plants servicing the entire population (1.8 million) of the capital, Budapest were sampled weekly. 24 h composite (n = 44) and grab samples (n = 21) were concentrated by an in-house flat sheet membrane ultrafiltration method. The efficiency and reproducibility of the method was comparable to those previously published. SARS-CoV-2 RNA was quantified using RT-qPCR of the N gene. The first positive signal in sewage was detected 2 weeks before the rise in case numbers. Viral concentration and volume-adjusted viral load correlated to the weekly new cases from the same week and the rolling 7-day average of active cases in the subsequent week. The correlation was more pronounced in the ascending phase of the outbreak, data was divergent once case numbers plateaued. Wastewater surveillance was found to be effective in predicting the second wave of the outbreak in Hungary. Data indicated that even relatively low frequency (weekly) sampling is useful and at the same time, cost effective tool in outbreak detection.

Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer.

OBJECTIVES: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer. METHODS: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices. RESULTS: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI. CONCLUSIONS: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Health risk of swimming pool disinfection by-products: a regulatory perspective.

While disinfection of swimming pools is indispensable for microbiological safety, it may lead to the formation of disinfection by-products. Most studies agree that inhalation exposure is the predominant pathway of the associated health risks, but assumptions are based on concentrations measured in water and evaporation models. Pool water and air were sampled in 19 swimming pools. Trihalomethanes were detected in all sites; chloroform being the most abundant species. Concentrations ranged between 12.8-71.2 µg/L and 11.1-102.2 µg/m3 in pool water and air, respectively. The individual lifetime carcinogenic risk associated with chloroform in swimming pools exceeded 10-6 in all age groups for recreational swimmers and 10-5 for elite swimmers and staff, even if the pool complied with the national standards. Inhalation exposure was estimated and found to be the most relevant, however, different mass transfer models from water measurements significantly under- or overestimated the health burden compared to direct calculation from the concentration in air. The observed health risks call for defining regulatory values and monitoring requirement of indoor air quality in swimming pools.

Uranium in groundwater - The importance of hydraulic regime and groundwater flow system's understanding.

Uranium and other natural radionuclides are common components in groundwater, but they are not routinely measured. In drinking water their total activity is screened, but in the evaluation of the measured values usually the aquifer material is only considered. However, the occurrence of radionuclides in groundwater is strongly affected by flow systems and their geochemical characteristics. Therefore hydrogeology and flow system's evaluation is crucial to understand natural radioactivity. Areas of different hydraulic regimes - recharge, throughflow and discharge - even within the same aquifer are characterized by different geochemical environment. In the present study pressure-elevation profiles were generated based on existing basic hydraulic data of wells in order to determine the flow regimes and associated vertical groundwater flow directions. 24-753 mBq L-1 uranium activity concentrations were found in groundwater and surface water showing great areal variability. High uranium values correspond to recharge regimes with downward flow directions. Uranium mobility is enhanced by high bicarbonate content and circumneutral pH. The study emphasize the importance of groundwater flow system's understanding in those areas, where elevated background radioactivity may exist.

Acetaldehyde level in spirits from central European countries.

Intake of acetaldehyde in alcoholic beverages, in central Europe, might explain the high rate of alcohol-related diseases in these countries. We measured the acetaldehyde level in 30 samples of home-made spirits and 12 samples of industry-made spirits from four central European countries, including 35 fruit-based and five grain-based spirits. Acetaldehyde was detected in all fruit-based spirits and in none of the grain-based spirits. Acetaldehyde levels were above 2000 µmol/l in 12 samples, 11 of which were home-made. In a multivariate analysis restricted to fruit-based spirits, however, the difference between home-made and industry-based spirits was not statistically significant. These results add evidence to the hypothesis that intake of acetaldehyde in alcoholic beverages, in central Europe, contributes to the burden of alcohol-related disease, especially that of upper digestive tract cancers. The acetaldehyde level should be monitored and high-level exposure should be avoided.

Environmental health aspects of drinking water-borne outbreak due to karst flooding: case study.

Climate change may increase the incidence of waterborne diseases due to extreme rainfall events, and consequent microbiological contamination of the water source and supply. As a result of the complexity of the pathways from the surface to the consumer, it is difficult to detect an association between rainfall and human disease. The water supply of a Hungarian city, Miskolc (174,000 inhabitant), is mainly based on karstic water, a vulnerable underground water body. A large amount of precipitation fell on the catchment area of the karstic water source, causing an unusually strong karstic water flow and flooding, and subsequent microbiological contamination. The presence of several potential sources of contamination in the protective zone of the karstic water source should be emphasized. The water supplier was unprepared to treat the risk of waterborne outbreak caused by an extreme weather event. Public health intervention and hygienic measures were taken in line with epidemiological actions, focusing on the protection of consumers by providing safe drinking water. The contamination was identified, and measures were taken for risk reduction and prevention. This case study underlines the increasing importance of preparedness for extreme water events in order to protect the karstic water sources and to avoid waterborne outbreaks.

Insulin induced translocation of Na+/K+ -ATPase is decreased in the heart of streptozotocin diabetic rats.

AIM: To investigate the effect of acute insulin administration on the subcellular localization of Na(+)/K(+)-ATPase isoforms in cardiac muscle of healthy and streptozotocin-induced diabetic rats. METHODS: Membrane fractions were isolated with subcellular fractionation and with cell surface biotinylation technique. Na(+)/K(+)-ATPase subunit isoforms were analysed with ouabain binding assay and Western blotting. Enzyme activity was measured using 3-O-methylfluorescein-phosphatase activity. RESULTS: In control rat heart muscle alpha1 isoform of Na(+)/K(+) ATPase resides mainly in the plasma membrane fraction, while alpha2 isoform in the intracellular membrane pool. Diabetes decreased the abundance of alpha1 isoform (25 %, P<0.05) in plasma membrane and alpha2 isoform (50%, P<0.01) in the intracellular membrane fraction. When plasma membrane fractions were isolated by discontinuous sucrose gradients, insulin-stimulated translocation of alpha2- but not alpha1-subunits was detected. Alpha1-subunit translocation was only detectable by cell surface biotinylation technique. After insulin administration protein level of alpha2 increased by 3.3-fold, alpha1 by 1.37-fold and beta1 by 1.51-fold (P<0.02) in the plasma membrane of control, and less than 1.92-fold (P<0.02), 1.19-fold (not significant) and 1.34-fold (P<0.02) in diabetes. The insulin-induced translocation was wortmannin sensitive. CONCLUSION: This study demonstrates that insulin influences the plasma membrane localization of Na(+)/K(+)-ATPase isoforms in the heart. alpha2 isoform translocation is the most vulnerable to the reduced insulin response in diabetes. alpha1 isoform also translocates in response to insulin treatment in healthy rat. Insulin mediates Na(+)/K(+)-ATPase alpha1- and alpha2-subunit translocation to the cardiac muscle plasma membrane via a PI3-kinase-dependent mechanism.