Associating Air Pollution with Cytokinesis-Block Micronucleus Assay Parameters in Lymphocytes of the General Population in Zagreb (Croatia).

Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health.

Geographic distribution and risk of upper urothelial carcinomas in Croatia, 2001-2011.

BACKGROUND: Strong associations exist between Balkan endemic nephropathy (BEN) and upper urothelial carcinomas (UUCs). However, the common etiology between the two remains unclear and there are no studies to date that visualize UUC risks in Croatia. In Croatia, 14 villages in the southwestern part of Brod-Posavina County are considered endemic for BEN. The aim of this ecological study is to map cancer risks and describe the case distribution of UUCs in Croatia at the county level during 2001-2011. METHODS: A total of 608 incident cases from the Croatian National Cancer Registry were identified. Indirect standardization was employed to compute standardized incidence ratios (SIRs). RESULTS: Counties with SIRs greater than 1 were concentrated around the agricultural region of Slavonia and the coastal region of Dalmatia. However, only Brod-Posavina County and Vukovar-Srijem County had a statistically significant risk of UUC development, where there were 390 and 210% more UUC cases observed than expected, respectively. Only unique to Brod-Posavina County, females were at higher risk (SIR 4.96; 95% CI 3.59-6.34) of developing UUCs than males (SIR 3.03; 95% CI 2.04-4.01) when compared to their Croatian counterparts. Although Brod-Posavina County only made up 3.7% of the total Croatian population (as of 2011), it had the highest frequency of incident UUC cases after the capital City of Zagreb. No elevated cancer risks were noted in the City of Zagreb, even after stratifying by sex. CONCLUSION: Our findings suggest that Brod-Posavina County had the highest cancer risk for UUCs, especially among females, when compared to Croatia as a whole during 2001-2011. Given that a majority of BEN patients develop associated UUCs, concurrent screening programs for UUCs and BEN should be considered not only in endemic areas of BEN but also the surrounding rural areas and amongst at-risk groups such as those undergoing hemodialysis, who frequently develop UUCs, to help clarify BEN-UUC associations by identifying common risk factors while standardizing disease estimates across endemic regions for BEN.

HEADACHES IN ADOLESCENTS - FREQUENCY, RISK FACTORS AND OTHER HEALTH COMPLAINTS: A CROSS-SECTIONAL STUDY IN CROATIA.

- Headaches are very common in school population. The aim of this study was to determine epidemiological data on headaches among Croatian schoolchildren and their connection to risk factors and other health complaints. In the study, we used the Croatian database of the international research entitled Health Behavior in School-aged Children for 2013/2014. It is a cross-sectional study conducted every four years in 44 countries among children aged 11-16. The students were interviewed using an anonymous standardized questionnaire. The Croatian sample consisted of 5741 students, of which 2857(49.8%) girls and 2884 (50.2%) boys. The response rate was 85.9%. Headaches were reported to be often (once a week to daily) by 23.5% of students and were more often in girls and in higher school grades. They were positively linked to cigarette smoking and health complaints such as back pain and stomachache, bad mood, nervousness, irritability, difficulties with sleeping and dizziness. Headaches are associated to many health problems and can cause difficulties in student functioning. This could be a serious problem. This study pointed to connection of headaches with cigarette smoking and importance to underpin the smoking prevention programs.

Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants.

BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.

National program of breast cancer early detection in Brod-Posavina County (East Croatia).

Results of the National Program of Breast Cancer Early Detection in Brod-Posavina County during the 2006-2012 period are presented. Response rate in two National Program cycles, cancers detected according to factors such as first and last menstruation, age at cancer detection, deliveries and mammography findings according to the Breast Imaging Reporting and Data System (BI-RADS) before diagnosis verification were analyzed. Data were obtained from the software connecting Public Health Institutes via Ministry of Health server and questionnaires filled out by the women presenting for screening and processed by the method of descriptive statistics. Mammography findings were classified according to the BI-RADS classification. In two National Program cycles during the 2006-2012 period, women aged 50-69 were called for mammography screening. In the first cycle, the response rate in Brod-Posavina County was 53.2%, with 71 cancers detected at a mean age of 61.3 years. In the second cycle, the response rate was 57.0%, with 44 cancers detected at a mean age of 62.5 years. In the first and second cycles, there were 21.1% and 14.3% of mammography findings requiring additional work-up (BI-RADS 0), respectively. Particular risk factors such as early menarche, late menopause, parity, positive family history and presence of benign breast lesions were not demonstrated in women with verified cancer. There was no increase in the incidence of breast cancer per 100,000 inhabitants in the Brod-Posavina County following implementation of the National Program. In conclusion, efforts should be focused on increasing public health awareness, ensuring appropriate professional staff engaged in screening, and improving medical care in order to reduce the time elapsed from establishing suspicion to confirming the diagnosis of breast cancer.

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Upper urothelium carcinomas in Croatian endemic area.

BACKGROUND/AIMS: Endemic nephropathy (EN) is a chronic tubulointerstitial disease. Strong association between EN and urothelial carcinoma was noted as early as 40-50 ago. The aim of the study was to determine and compare specific mortality and morbidity of renal pelvis and ureter (upper urothelium) carcinoma (UUC) among Croatia as a whole, Brod-Posavina County, and Croatian endemic area. METHODS: Data on UUC mortality and morbidity were analyzed. Indirect standardization was employed on data comparison by calculating standardized mortality ratio and morbidity ratio. RESULTS: Our study results showed the specific mortality rate in the endemic area to be 26.3-fold and 7.3-fold the rate recorded in Croatia and Brod-Posavina County, respectively. The mean standardized mortality ratio obtained by indirect standardization yielded an 8-fold and 32-fold risk of death from UUC in the endemic area vs. Brod-Posavina County and Croatia as a whole, respectively. These data revealed the specific morbidity in the Croatian endemic area and Brod-Posavina County to be 13.95-fold and 3.78-fold the morbidity recorded at the national level, respectively. The standardized morbidity ratio also showed the risk of developing UUC in the Croatian endemic area to be 3.75-fold the risk in Brod-Posavina County and 16.4-fold the risk in Croatia. CONCLUSIONS: These results showed that specific mortality and morbidity as well as standardized morbidity ratio and standardized mortality ratio were higher in Croatian endemic area than in Brod-Posavina County and Croatia.

National program of colorectal carcinoma early detection in Brod-Posavina County (east Croatia).

Colorectal carcinoma (CRC) is a major public health problem as the third leading malignant tumor in men and fourth in women in Croatia. Prognosis and treatment greatly depend on tumor stage at the time of detection. Therefore, the National Program of Colorectal Carcinoma Early Detection has been performed since 2007. The aim is to present the response rate, colonoscopy findings and number of newly detected CRC cases in Brod-Posavina County. During five years of the National Program performance, 28 CRC cases were detected in Brod-Posavina County, with the 3.3% rate of carcinoma detection. The majority of CRC cases were found in the 50-64 age group. The response rate in the County was low (20.4%), corresponding to the national rate but far from the recommended one. Such a result could be attributed to the low level of awareness in the population at large, complex testing technique for general population, fear from disease detection and from colonoscopy as a diagnostic procedure. Note should be made of the underestimated role of family physicians; their involvement in the National Program should certainly result in better response rate in our County as well as at the national level.

[Mineral oil drinking water pollution accident in Slavonski Brod, Croatia]. / Zagadenje pitke vode mineralnim uljima u Slavonskom Brodu.

On 21 September 2008, heavy oil penetrated the drinking water supply in Slavonski Brod, Croatia. The accident was caused by the damage of heat exchange units in hot water supply. The system was polluted until the beginning of November, when the pipeline was treated with BIS O 2700 detergent and rinsed with water. Meanwhile, water samples were taken for chemical analysis using spectrometric and titrimetric methods and for microbiological analysis using membrane filtration and total plate count. Mineral oils were determined with infrared spectroscopy. Of the 192 samples taken for mineral oil analysis, 55 were above the maximally allowed concentration (MAC). Five samples were taken for polycyclic aromatic hydrocarbon (PAH), benzene, toluene, ethylbenzene, and xylene analysis (BTEX), but none was above MAC. Epidemiologists conducted a survey about health symptoms among the residents affected by the accident. Thirty-six complained of symptoms such as diarrhoea, stomach cramps, vomiting, rash, eye burning, chills, and gastric disorders.This is the first reported case of drinking water pollution with mineral oil in Slavonski Brod and the accident has raised a number of issues, starting from poor water supply maintenance to glitches in the management of emergencies such as this.

Visual assessment of endemic nephropathy markers relationship.

The aim of this paper was to assess relationship between possible endemic nephropathy (EN) markers visually by the CoPlot methodology, and to illustrate this promising data analysis approach. From 912 screened persons in 3 Croatian endemic villages, 25 persons were diagnosed as confirmed EN patients, 371 as non-EN, and the remainder were classified as suspected of having EN, or at risk. Data on 25 confirmed EN patients were matched with appropriate non-EN examinees. All records with missing data were excluded, resulting in 35 subjects with complete data on the 13 key EN variables for CoPlot mapping. CoPlot solution met the accepted goodness of fit measure thresholds. Result showed relationship between EN markers, identifying some nearly duplicated variables, and possible outliers needing some subsequent analysis.