Associations of TNFα -308G>A, TNFα -238G>A, IL-1α -889C>T and IL-10 -1082G>A Genetic Polymorphisms with Atopic Diseases: Asthma, Rhinitis and Dermatitis.

BACKGROUND: Polymorphisms of cytokine genes are an interesting focus for association studies involving atopic diseases due to their role in immune cell communications during inflammation. The aim of this study was to investigate associations of TNFα -308G>A, TNFα -238G>A, IL-1α -889C>T and IL-10 -1082G>A polymorphisms with atopic diseases with adjustment for confounding lifestyle and environmental factors. METHODS: This study was performed on 356 Croatian students. The diagnosis of atopic asthma, atopic rhinitis and atopic dermatitis was based on symptoms reported by the modified International Study of Asthma and Allergies in Childhood questionnaire and a positive skin prick test (SPT) to at least one common inhalatory allergen. Genetic polymorphisms were genotyped using the polymerase chain reaction-based technique. The influence of personal (gender, body mass index, parental history of atopic disease), lifestyle (cigarette smoking, pet ownership) and environmental (urban/rural residency, residency in continental/Mediterranean region) factors reported in the questionnaire was investigated by univariate and multivariate analysis. RESULTS: Compared to the control subjects, univariate analysis showed a significant negative association of the TNFα -308G>A polymorphism with atopic asthma, atopic dermatitis, asthma and skin symptoms and positive SPT. These observations were confirmed in a multivariate model only for atopic dermatitis and skin symptoms (atopic dermatitis: OR = 0.27; 95% CI 0.07-1.00; p = 0.050; skin symptoms: OR = 0.29; 95% CI 0.10-0.83; p = 0.021). CONCLUSIONS: The results indicate a protective role of TNFα -308G>A genetic polymorphisms regarding atopic dermatitis and skin symptoms even after controlling for personal, lifestyle and environmental factors. Further studies are needed to elucidate the molecular patterns of this association in atopic dermatitis and other chronic inflammatory skin disorders.

A graphical model approach to systematically missing data in meta-analysis of observational studies.

When studies in meta-analysis include different sets of confounders, simple analyses can cause a bias (omitting confounders that are missing in certain studies) or precision loss (omitting studies with incomplete confounders, i.e. a complete-case meta-analysis). To overcome these types of issues, a previous study proposed modelling the high correlation between partially and fully adjusted regression coefficient estimates in a bivariate meta-analysis. When multiple differently adjusted regression coefficient estimates are available, we propose exploiting such correlations in a graphical model. Compared with a previously suggested bivariate meta-analysis method, such a graphical model approach is likely to reduce the number of parameters in complex missing data settings by omitting the direct relationships between some of the estimates. We propose a structure-learning rule whose justification relies on the missingness pattern being monotone. This rule was tested using epidemiological data from a multi-centre survey. In the analysis of risk factors for early retirement, the method showed a smaller difference from a complete data odds ratio and greater precision than a commonly used complete-case meta-analysis. Three real-world applications with monotone missing patterns are provided, namely, the association between (1) the fibrinogen level and coronary heart disease, (2) the intima media thickness and vascular risk and (3) allergic asthma and depressive episodes. The proposed method allows for the inclusion of published summary data, which makes it particularly suitable for applications involving both microdata and summary data. Copyright © 2016 John Wiley & Sons, Ltd.

Skin health and safety at work in Croatian hairdressing apprentices.

BACKGROUND: The risk of developing occupational skin disease (OSD) is high in hairdressers, but may differ between countries. OBJECTIVE: To evaluate safety at work measures, and the prevalence and severity of skin symptoms and their impact on quality of life (QoL), among Croatian hairdressing apprentices. METHODS: Data on self-reported skin symptoms, safety measures and QoL were collected for 101 final-year apprentices. The presence and severity of skin lesions were assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). Transepidermal water loss (TEWL) was measured on the forearm and hand. RESULTS: Ninety-one percent of apprentices reported wearing gloves while dyeing hair, 45% while rinsing hair dyes, and 4% while washing hair. A history of skin symptoms was found in 35% of apprentices, and a history of dry hands in 37%. Skin changes were clinically observed in 40% of apprentices, most frequently erythema, infiltration, and desquamation. The OHSI score ranged from 0 to 6. Only washing hands >20 times per day was positively associated with TEWL. A history of skin symptoms negatively correlated with self-esteem, and social and mental functioning, and positively with anxiety and depression. CONCLUSIONS: The results indicate the need for the continuation of efforts to establish effective primary preventive programmes for OSDs at national and EU levels.

Occupational and non-occupational allergic contact dermatitis: a follow-up study.

BACKGROUND/AIMS: The aim of this study was to obtain insight into the clinical course and prognosis of allergic contact dermatitis (ACD), including potential effects of genetic and environmental factors. METHODS: Eighty-two patients with previously defined ACD acquired occupationally (OACD) or non-occupationally (NOACD) were patch retested and evaluated for the presence of persistent eczema, atopy and filaggrin mutations. RESULTS: The crude risk for the persistence of a positive patch test (PT) reaction was 6.3 times higher (95% CI 3.63-11.0) for PT reactions assessed as '+++' compared to '++' reactions at the first PT. Among the categories of OACD, NOACD, age, gender, atopy, and the number of positive PT reactions at the first and second PT, only OACD (OR 10.0, 95% CI 1.95-51.2) and number of positive PT reactions at retesting (OR 3.85, 95% CI 1.57-9.44) were found to be predictors of persistent eczema. CONCLUSIONS: Occupationally acquired contact allergy was emphasized as the most important factor in predicting poor prognosis of ACD.

Respiratory health and breath condensate acidity in sawmill workers.

PURPOSE: The aim of the study was to evaluate exhaled breath condensate acidity (EBC pH) as a biomarker of airway response to occupational respiratory hazards present in sawmill. METHODS: Sixty-one sawmill workers in total (26 from Sawmill 1 and 35 from Sawmill 2) provided EBC samples at the beginning and at the end of the working week. Respiratory symptoms, lung function, bronchodilator test and atopy status were assessed. Occupational environment was checked for the levels of respiratory hazards. RESULTS: Airborne dust concentrations were below threshold limit value. Endotoxin in Sawmill 1 and Sawmill 2, and moulds in Sawmill 1 were at the levels able to induce inflammatory response in the airways. Mould levels were 2.5 times higher in Sawmill 1 than in Sawmill 2. Compared to Sawmill 2 workers, lower spirometry values, higher prevalence of dry cough and positive bronchodilator test were found in Sawmill 1 workers. Monday EBC pH values did not differ between sawmills, but declined after one working week in Sawmill 1 workers (from 7.88 to 7.49, P = 0.012) and not in Sawmill 2 workers. Similar results were obtained when only respiratory healthy non-smokers were analysed. Monday-to-Friday change of other respiratory parameters was not observed. CONCLUSION: The results suggest EBC pH as a biomarker of acute respiratory effects related to occupational exposure to respiratory hazards in sawmills, presumably increased mould levels. The effect was present even at subclinical level, namely in respiratory healthy subjects. The long-term health implications remain unclear and should be evaluated in a follow-up study.

Wi-Fi technology and human health impact: a brief review of current knowledge.

An enormous increase in the application of wireless communication in recent decades has intensified research into consequent increase in human exposure to electromagnetic (EM) radiofrequency (RF) radiation fields and potential health effects, especially in school children and teenagers, and this paper gives a snap overview of current findings and recommendations of international expert bodies, with the emphasis on exposure from Wi-Fi technology indoor devices. Our analysis includes over 100 in vitro, animal, epidemiological, and exposure assessment studies (of which 37 in vivo and 30 covering Wi-Fi technologies). Only a small portion of published research papers refers to the "real" health impact of Wi-Fi technologies on children, because they are simply not available. Results from animal studies are rarely fully transferable to humans. As highly controlled laboratory exposure experiments do not reflect real physical interaction between RF radiation fields with biological tissue, dosimetry methods, protocols, and instrumentation need constant improvement. Several studies repeatedly confirmed thermal effect of RF field interaction with human tissue, but non-thermal effects remain dubious and unconfirmed.

Prevention of poisonings by educational intervention aimed at parents of preschool children.

The aim of the study was to assess the effectiveness of the specific design of a poisoning prevention intervention. This controlled before-after study followed Solomon design for educational interventions using two groups (the educational intervention group and the control group). Participants comprised parents of children attending kindergartens under the jurisdiction of the City of Zagreb and in the vicinity of Zagreb. The intervention group (N = 336) underwent an educational intervention during parents' meetings comprising oral presentation by the Croatian Poison Control Centre (CPCC) and distribution of gift packages containing child-proof locks, flyers, and stickers with the CPCC contact number. After the intervention they more frequently started keeping the CPCC's number by their telephone or in the list of important numbers than parents in the control group, and this association remained significant when tested by generalized estimating equations for binary outcomes, after the adjustment for parents' characteristics (age, gender and educational level), and clustered by kindergartens (p < 0.001). This means parents acknowledged the CPCC as an adequate and accessible way for initial management of poisoning incidents.

Employment status and other predictors of mental health and cognitive functions in older Croatian workers.

The aim of this study was to examine mental health and cognitive functions in older Croatian workers (50-65 years) taking into account their employment status, self-assessed health, and a set of demographic characteristics. We analysed the data collected on 650 older workers (71 % employed) in the Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Unemployed workers reported symptoms of loneliness more often than the employed, while in rural areas unemployment was additionally associated with more pronounced symptoms of depression. Feeling of loneliness was also higher in those living without a partner in the household and in those with poorer health. In urban residents symptoms of depression were more severe in women, respondents with higher education, those living without a partner, and those who rated their health as poorer. As for cognitive functions, unemployment significantly predicted poorer subtraction in the rural subsample. Women in general showed less efficient numerical abilities. In the urban subsample poorer numerical abilities were also associated with lower education and living without a partner in the household. Better verbal recall was predicted by higher education and better self-rated memory. Higher scores in verbal fluency were predicted by urban residency and better self-rated health. Our results indicate that the protective factors for good mental health and cognitive functioning in older Croatian workers are being employed, having more education, living with a partner in the household, and being healthier. These findings stress the importance of implementing broader social policy strategies covering employment, education, and health.

Association of toxic and essential metals with atopy markers and ventilatory lung function in women and men.

The association of age, smoking, alcohol, superoxide dismutase (SOD), glutathione peroxidase (GPx), blood lead (BPb) and cadmium (BCd) levels, and serum levels of copper (SCu), zinc (SZn) and selenium (SSe) with atopic status and ventilatory function was examined in the groups of 166 women and 50 men with no occupational exposure to metals or other xenobiotics. Markers of atopy included serum total IgE, skin prick test (SPT) to common inhalatory allergens, non-specific nasal reactivity (NNR) and non-specific bronchial reactivity (NBR). Parameters of ventilatory function included forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)). Significantly higher BPb, SZn, IgE and prevalence of positive SPT, and lower SCu and NNR was found in men than in women. Fifteen women taking female sex hormones (HT) had significantly higher SCu than women without HT. Regression models showed significant inverse associations between IgE and SCu (P=0.021) and NNR and SCu (P=0.044) in women. When excluding women with HT, the association of SCu and total IgE became of borderline significance (P=0.051), association between SCu and NNR disappeared, and significant positive association between total IgE and BPb emerged (P=0.046). In men, significant inverse association was found between positive SPT and SSe, and between NBR and SSe. A decrease in FVC% and FEV(1)% was associated with an increase in smoking intensity (P<0.001) and a decrease in SZn (P=0.043 and P=0.053, respectively). These results were observed at the levels of the metals comparable to those in general populations worldwide. The observed differences between men and women may partly be explained by different levels of relevant toxic and essential metals, and their combination. The role of female HT in associations of atopy markers and SCu should be further investigated.

[Health effects of pyrethrins and pyrethroids]. / Zdravstveni ucinci piretrina i piretroida.

Pyrethrins, natural extracts of Chrysanthemum cinerariaefolium and Chrysanthemum cocineum flowers, and pyrethroids, synthetic analogues and derivatives of pyrethrins, are powerful insecticides. They are widely used in households and insect control in pets or livestock, in textiles such as carpets, wallpapers, furniture and clothes, as well as in agriculture, forestry and public health services. This article brings a list of pyrethrin and pyrethroid insecticides registered for use in plant protection in Croatia. Pyrethrins and pyrethroids can enter the organism by ingestion (accidental or suicidal ingestion or in food), by inhalation and/or by skin contact. Although these pesticides pose a relatively low risk to mammals due to rapid metabolism with no significant accumulation, they can induce adverse health effects, more often in acute poisoning, but also due to chronic exposure. The primary target of pyrethrin and pyrethroid toxicity is the nervous system, since they act directly on the sodium channels of nerve cell axons, leading to hyperexcitation. Another important toxicological mechanism is allergenicity, which is more pronounced with pyrethrins than with synthetic pyrethroids. Because there is no antidote for pyrethrin and pyrethroid poisoning, treatment is symptomatic and supportive. The article discusses the measures for poisoning prevention and alleviation of exposure to pyrethrins and pyrethroids in occupational settings and in general population.

[Household gas poisonings]. / Otrovanja plinovima u kucanstvu.

Exposure to toxic gases which can induce serious health effects, can occur in the working as well as in general environment, including home. The severity of gas poisoning is determined by its physical and chemical characteristics, intensity and duration of exposure, and concomitant diseases and injuries in the poisoned person. Manifestations of gas toxic action involve simple asphyxia, local irritation of respiratory mucosa, systemic toxicity, and a combination of these mechanisms. This article describes the characteristics, modes of exposure and health effects of most common gases causing poisoning at home. These include gas fuels, carbon monoxide, ammonia, chlorine, and fire gases such as nitrogen and sulphur oxides, hydrogen cyanide and phosgene. First aid as well as preventive measures to avoid exposure to toxic gases and prevent fire at home are also given. The Croatian Poison Control Centre gathered data on toxic gas exposures in households between November 2005 and July 2006. During this period 30 persons (3 % of the total number of cases) were exposed to toxic gases at home, including carbon monoxide, irritating vapours from cleaning agents and disinfectants, gas fuels, septic tank gases, tear-gas, and chlorofluorocarbons from refrigerators.

Use of human milk in the assessment of toxic metal exposure and essential element status in breastfeeding women and their infants in coastal Croatia.

Pregnant and lactating women and infants are vulnerable population groups for adverse effects of toxic metals due to their high nutritional needs and the resultant increased gastrointestinal absorption of both, essential and toxic elements. Although breastfeeding is recommended for infants worldwide, as human milk is the best source of nutrients and other required bioactive factors, it is also a pathway of maternal excretion of toxic substances including toxic metals and thus a source of infant exposure. The aim of this research was to assess health risks in breastfeeding women in the coastal area of the Republic of Croatia and their infants (N=107) due to maternal exposure to Cd and Pb via cigarette smoking, and Hg via seafood and dental amalgam fillings, and their interaction with essential elements. Biological markers of exposure were the concentrations of main toxic metals Pb, Cd and Hg in maternal blood and three types of breast milk throughout lactation stages. Biological markers of effects were the levels of essential elements Ca, Fe, Cu, Zn and Se in maternal serum and breast milk. With regard to cigarette smoking as a source of exposure to Cd and Pb, there were effects of smoking on Cd concentration in blood and correlations between the smoking index and Cd concentrations in maternal blood (ρ=0.593; P<0.001) and mature milk (ρ=0.271; P=0.011) and Pb concentration in transitional milk (ρ=0.280; P=0.042). Regarding fish, we found correlations between weekly consumption frequency and total Hg concentrations in maternal blood (ρ=0.292; P=0.003) and mature milk (ρ=0.303; P=0.003). The number of dental amalgam fillings correlated with total Hg concentrations in colostrum (ρ=0.489; P=0.005) and transitional milk (ρ=0.309; P=0.018). As for the essential element status, only Se levels in maternal serum decreased by 10% in persons who continued smoking during pregnancy compared to non-smokers. In conclusion, the levels of main toxic metals Cd, Pb and Hg and essential elements Ca, Fe, Cu, Zn and Se in maternal blood and three types of breast milk samples in the studied area of coastal Croatia showed no risk of disrupted essential element levels with regard of toxic metal exposure in both breastfeeding women and their infants.

Soluble CD14 and total IgE in the serum of atopic and nonatopic adolescents in relation to environmental factors: a pilot study.

The CD14 receptor is expressed on the surfaces of monocytes, macrophages, and, to a lesser extent, of activated granulocytes and B lymphocytes (mCD14). It also exists in soluble form in the serum (sCD14), in which it binds microbial compounds and indoor allergens. The objectives of this study were to see whether serum sCD14 concentrations could be used as a marker of atopic disorders and to estimate the effects of environmental factors (tobacco smoke exposure, childhood residence in urban or rural areas, and having a pet) on sCD14 and IgE values. Mass fraction of sCD14 and total IgE were determined in the sera of atopic (N=53) and non-atopic (N=35) participants using the standard enzyme-linked immunosorbent assay. Exposure to pets and environmental tobacco smoke was estimated based on the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC). Median sCD14 concentration was significantly lower in atopic than in non-atopic girls (3.49 vs. 3.83 µg mL(-1); p<0.010). The number of smokers at home positively correlated with the sCD14 level in atopics, and urban atopics had significantly lower sCD14 levels than rural atopics (3.47 vs. 3.92 µg mL(-1), p=0.028). Median total IgE concentration was significantly lower in atopic pet owners than in atopics with no pets (161 vs. 252 kIU L(-1); p=0.021). In conclusion, while sex and environmental factors might be involved in sCD14 expression, particularly in atopics, we found no correlation between sCD14 and total IgE concentrations. The usefulness of sCD14 as a marker of atopic disorders should be investigated further, particularly in relation to the severity of allergic disorders.

Combined early treatment with chelating agents DMSA and CaDTPA in acute oral cadmium exposure.

The influence of chelating agents: meso-2,3-dimercaptosuccinic acid (DMSA); calcium trisodium diethylenetriaminepentaacetate (CaDTPA) and their combination on mobilisation of cadmium (Cd) was compared in female albino rats. After oral Cd administration chelators were applied either orally (DMSA) or intraperitoneally (CaDTPA) at various short time intervals after Cd. Three experiments were carried out with four treatment groups in each: 1) Cd (control); 2) Cd+DMSA; 3) Cd+CaDTPA; 4) Cd+DMSA+CaDTPA. Time intervals for chelator treatment after Cd administration were: immediate application in the first, half an hour in the second and one hour in the third experiment. At the end of each experiment cadmium was analysed in kidney and liver. Additionally in experiment 3 essential elements (Fe, Cu, Zn) were also determined in the same organs. In experiment 2 the effect of the treatment on urinary elimination of cadmium, copper and zinc were analysed. Results showed that the efficiency of Cd removal from the body (kidneys and liver) is lower when the time between Cd and chelating agents administration is longer. The two chelators differ in efficiency in mobilizing Cd, with DMSA being more efficient than CaDTPA. The combined therapy with the two chelators gave generally better results. It seems that DMSA which is given orally after oral Cd administration removes this element very efficiently from the gastrointestinal tract. CaDTPA, however, which is given parenterally removes absorbed Cd less efficiently, Organs are not significantly depleted in iron and copper after chelation treatment. Only zinc concentration was, however, significantly lower in the liver and higher in kidneys only after CaDTPA and combined DMSA+CaDTPA chelation.

Endotoxin measurement in house dust using the end-point Limulus amoebocyte lysate method.

Endotoxin is a lipopolysaccharide, a part of gram-negative bacteria cell membrane commonly present in general and many occupational environments. This paper describes sample preparation and endotoxin measurement in 16 samples of house dust from urban homes (Zagreb, Croatia) using end-point chromogenic Limulus amoebocyte lysate (LAL) bioassay. House dust was collected on cellulose filters by vacuuming bedroom and living room floors, and was kept frozen until assayed. Samples were extracted from filters with a 0.05% solution of Tween-20 in endotoxin-free water. Serial dilutions of samples were measured in duplicates. The linearity of the standard curve was satisfying (r=0.983), as well as the recovery (92 and 110%) and repeatability (coefficient of variation from 0 to 8.5%). The endotoxin levels found in the house dust samples ranged from 4.8 to 200 EU/mg, with the arithmetic mean of 49.5 EU/mg (standard error of the mean of 12.1 EU/mg), and were in the range of house dust endotoxin values obtained by other authors.

Commercial rodent feed as an occasional cause of morbidity and mortality in a rat breeding colony.

In the last fifteen years there were several feed-related outbreaks of morbidity and mortality in the Institute's breeding colony of Wistar rats. The last event took place in April 1999, one month after the use of a new supply of the usual standard rodent feed. Animals did not thrive and manifested generalised oedema, hypoalbuminaemia, elevated liver enzymes, and high mortality. The effect of feed was assessed first by feeding a group of sick females during 14 days with either suspected feed (A-March) or with the earlier supply of feed (A-January) of the same producer. Then a group of healthy male rats Y59 from another breeding colony was fed either suspected feed (A-March) or feed from another producer (feed B). Although neither chemical nor microbiological deviation in feed analysis had been detected, decreased consumption and slower body weight gain in all animals fed with feed A-March suggested an association between this batch of feed and the increased morbidity in those animals. Eventually, the entire rat colony was put down and replaced with a new breed which was given a new brand of feed.

The effect of dietary supplementation with calcium salts on skeletal calcium in suckling rats.

This study aimed at identifying a calcium compound which could serve as an effective and safe dietary supplement in suckling rats over the period of intense growth and development. The main objective was to assess the effect of additional calcium intake on skeletal calcium in suckling pups. Suckling Wistar rats were fed using a pipettor with one of the following calcium salts from day 6 to 14 after the birth: gluconate, hydrogenphosphate, carbonate (each suspended in cow's milk), or chloride (in demineralized water). Control rats received only cow's milk. Calcium in the carcass (body without organs and skin) was analysed by atomic absorption spectrometry. The only effective dietary supplement that produced no risk for the suckling pups' growth was calcium hydrogenphosphate in cow's milk in the total amount of 340 mg. That dose increased the daily calcium intake 3 to 4 times compared to non-supplemented controls, increasing carcass calcium content by about 16 per cent. Other calcium compounds were either inefficient (carbonate) or had adverse effects on pups' growth (chloride and gluconate).

Exhaled breath condensate pH and FeNO as biomarkers of acute and chronic exposure to hazards at swine farms.

OBJECTIVE: The noninvasive biomarkers of respiratory impairment were assessed in 15 swine confinement (SC) workers and 9 respiratory healthy, nonsmoking volunteers (HV). METHODS: Spirometry, fraction of exhaled nitric oxide (FeNO), and exhaled breath condensate (EBC) pH were assessed in SC workers after one working shift and one working week and in HV after 5-hour exposure in SC. RESULTS: Half of the respiratory symptoms (in 8 of 15 SC workers) were work-related. Basal FeNO values were 7.5 ppb higher in the SC workers compared with HV. In the SC workers, EBC pH increased for 0.17 at the end of a working week (P < 0.001). In HV, 5-hour exposure in SC induced 8% drop in forced expiratory flow at 25% of the pulmonary volume (FEF25) (P = 0.008), EBC pH drop for 0.10 units (P = 0.003), and FeNO drop by 1.8 ppb (P = 0.047). CONCLUSIONS: EBC pH was suggested as a biomarker of acute airway acidification in HV, whereas the SC workers showed signs of the "healthy worker effect."