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Probabilistic exposure and risk assessment of chemical hazards in the diet have increasingly gained ground in recent years as a pragmatic approach for the approximation of reality. This work presents the outcomes of a project which aimed at applying probabilistic techniques for basic modelling of chronic dietary exposure to food contaminants following EFSA guidance. These techniques, based on Monte Carlo Risk Assessment (MCRA) software and on the programming language

BACKGROUND The increase in bacteria that are resistant to antimicrobials-often selected for a high level of antimicrobial uses (AMUs) in human beings or food-producing animals-is a global concern. The Austrian Poultry Health Service (QGV) has established a database containing comprehensive information on poultry flocks in Austria. METHODS AMU in 32,411 broiler flocks and 2946 turkey flocks between 2013 and 2019 is analysed by calculating different metrics, including the treatment incidence TI1000 . Furthermore, the Austrian benchmarking system for poultry is introduced. RESULTS Annual AMU in broilers decreased from 1030.8 kg of active ingredient to 762.5 kg between 2013 and 2016 but rose again to 1165.0 kg in 2019; while for turkeys annual AMU dropped from 1196.4 kg to 569.0 kg between 2013 and 2019. At the same time, the proportion of treated flocks decreased from 34.2% to 24.8% for broilers and from 54.3% to 44.0% for turkeys. In both broilers and turkeys, the most frequently used antimicrobial class, according to the TI1000 unit, in broilers and turkeys is polymyxins. CONCLUSION Calculating different metrics enables a deeper insight into AMU. Total AMU reduced without legislation but the increase of AMU in broiler production needs further investigation.

Nitrates occur in food naturally, as contaminants or additives. The health implications attributed to ingested nitrates result primarily from their conversion into nitrites and subsequent methemoglobinemia, carcinogenicity induced by N-nitroso-compounds and cardiovascular, endocrine, metabolic, reproductive and developmental effects. The present study comprises a probabilistic tiered risk assessment of nitrates for Austrian adults through the diet with the application of the Monte Carlo simulation method in alternative optimistic and pessimistic scenarios. Risk estimates are of concern regarding the upper exposures, which exceed the Acceptable Daily Intake (ADI) in almost all scenarios and population groups. Exposure is elevated when all dietary sources are considered and the ADI is exceeded by already the mean intake for vegetarians. Leafy vegetables are major contributors to the intake. Contribution of cured meat is very low. Estimates of the conversion of nitrates into nitrites were used to assess the combined exposure to both species. When the average intake of nitrates and nitrites is considered, the mean exposure to nitrites is lower or close to the ADI for individuals with average conversion capacity. However, upper tail combined intake can lead to a multifold exceedance of the ADI of nitrites for individuals with both high and average conversion capacity.

Bee viruses pose a considerable risk for the health of honeybee colonies all over the world. In this project we aim to collect representative data for eight bee viruses in Austrian honeybee colonies to identify the most problematic virus species. Additionally, we want to raise the awareness of beekeepers for virus infections and to encourage them to integrate preventive measures into their beekeeping routine. In September 2018, 198 beekeepers sampled bees from five of their colonies and sent the living bees to AGES (Austrian Agency of Health and Food Safety Ltd.) for analysis. Bees were killed by freezing upon arrival and analysed for the presence and virus titer of eight honeybee viruses by quantitative real-time RT-PCR. Six of the eight viruses were detected in the samples. The prevalence varied strongly between the viruses, some of them nearly ubiquitous and others rare. However, the presence of the viruses did not correlate with health status of the colonies. This demonstrates that viruses are widely present in Austrian apiaries as covert infections, as has been described for other European countries. The presence of an infection in a seemingly healthy colony was a new information for many of the participating beekeepers. They were informed about preventive beekeeping measures to avoid an outbreak of an overt virus infection. The project will be continued until 2021, including two additional samplings.

Objective We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation. Design Population-based prospective cohort study. Setting Ten public hospitals in the Austrian province of Styria. Sample A total of 87 065 neonates delivered in the period 2004–2015. Methods Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. Main outcome measures Neonatal composite adverse and severely adverse outcome measures. Results The odds ratio for severely adverse events during the night-time (22:01–07:29 hours) compared with the daytime (07:30–15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13–1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500–1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. Conclusions Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. Tweetable abstract Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.

Through our daily diet, we are exposed to a variety of food contaminants. Yet, assessing the cumulative health risk of chemical mixtures remains a challenge. Using a recently developed method, the modified Reference Point Index (mRPI), the cumulative risks posed by contaminant mixtures were assessed for their effects on reproduction and development. Since these effects can be quite diverse, a tiered approach was adopted to elucidate the risks at a more detailed level based on specific toxicological endpoints. An additional analysis was performed using the modified Maximum Cumulative Ratio (mMCR), which provides the determination of risk-dominating substances in the mixture. Our method represents a novel useful tool to screen and prioritise contaminant mixtures regarding their potential health risks. We found, that in the majority of the calculated scenarios a single substance dominates the cumulative risks. Lead was found to be the primary factor for adverse effects on reproduction and neuronal development of children. Perchlorate was identified as the most prominent risk factor for child development in generalCumulative risks of trichothecenes were dominated by deoxynivalenol. Concerning the impact on pre- and neonatal development, the co-exposure of several substances resulted in increased risks, with none of the considered contaminants dominating substantially.

Nitrites are present in the food chain as naturally occurring species or contaminants. Additionally, sodium and potassium nitrites are authorised food additives. Nitrites exert acute toxicity through methemoglobinemia or cardiovascular effects, chronic toxicity associated with endocrine, reproductive and developmental effects and have been classified as probable gastric carcinogens. Ingestion of food and water are the main sources of human exposure. This study comprises a tiered risk assessment of nitrites for the Austrian adult population, along with the identification of the food categories most contributing to their intake. The dietary exposure, based on Austrian occurrence and consumption data, was modelled with the Monte Carlo simulation method. In an additional scenario, data gaps were addressed with the usage of occurrence data published by the European Food Safety Authority and from the available literature to account for the exposure from all sources. Risk estimates regarding only the exposure to nitrite additives and to contaminated water indicate low level of concern. However, when exposure from all sources is considered, the estimated exposure is elevated and exceeds the Acceptable Daily Intake for high consumers. Mean exposure attributed to the use of nitrites as additives accounts for only a very small proportion of the total intake.

Risk assessment of chemical mixtures remains a challenging task in all areas of food and consumer safety. So far, no general method has been developed that is best suited to several subject areas (e.g. food contaminants, additives and supplements, plant protection products). Especially for mixtures of food contaminants sophisticated methods are typically not applicable due to a general lack of complete toxicological data sets. We developed a new approach, the modified Reference Point Index (mRPI), that combines the advantages of the Hazard Index and the Reference Point Index. Furthermore, we developed a decision tree for the determination of specific uncertainty factors that makes the mRPI an easy to use method for cumulative risk assessment even in a data poor field such as food contaminants. To further characterise the estimated cumulative risks, the Maximum Cumulative Ratio (MCR) was adapted to be applied on the mRPI, and the modified Maximum Cumulative Ratio (mMCR) was established to identify whether the risks are dominated by a single substance. We present two case studies assessing the nephrotoxic and neurotoxic risks for the Austrian population originating from food contaminant mixtures. Calculations could not rule out potential cumulative risks, yet, they seemed to be dominated by single substances.

Austrian beekeepers frequently suffered severe colony losses during the last decade similar to trends all over Europe. This first surveillance study aimed to describe the health status of Austrian bee colonies and to analyze the reasons for losses for both the summer and winter season in Austria. In this study 189 apiaries all over Austria were selected using a stratified random sampling approach and inspected three times between July 2015 and spring 2016 by trained bee inspectors. The inspectors made interviews with the beekeepers about their beekeeping practice and the history of the involved colonies. They inspected a total of 1596 colonies for symptoms of nine bee pests and diseases (four of them notifiable diseases) and took bee samples for varroa mite infestation analysis. The most frequently detected diseases were three brood diseases: Varroosis, Chalkbrood and Sacbrood. The notifiable bee pests Aethina tumida and Tropilaelaps spp. were not detected. During the study period 10.8% of the 1596 observed colonies died. Winter proved to be the most critical season, in which 75% of the reported colony losses happened. Risks for suffering summer losses increased significantly, when colonies were weak in July, had queen problems or a high varroa mite infestation level on bees in July. Risks for suffering winter losses increased significantly, when the colonies had a high varroa mite infestation level on bees in September, were weak in September, had a queen older than one year or the beekeeper had few years of beekeeping experience. However, the effect of a high varroa mite infestation level in September had by far the greatest potential to raise the winter losses compared to the other significant factors.

Objective We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation. Design Population-based prospective cohort study. Setting Ten public hospitals in the Austrian province of Styria. Sample A total of 87 065 neonates delivered in the period 2004–2015. Methods Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. Main outcome measures Neonatal composite adverse and severely adverse outcome measures. Results The odds ratio for severely adverse events during the night-time (22:01–07:29 hours) compared with the daytime (07:30–15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13–1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500–1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. Conclusions Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. Tweetable abstract Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.

Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis and progression of cancer; nevertheless clinical data for head and neck squamous cell carcinoma (HNSCC) are not available. The aim of our study was to associate tumor and clinical characteristics with status of vitamin D [25-hydroxyvitamin D (25(OH)D)]. 88 patients with newly diagnosed squamous cell carcinoma of the head and neck were included in the study. A blood draw was taken at the time of diagnosis. The observation period lasted from 2006 until 2010. Results: When compared to a cohort from an epidemiological study, serum levels of 25(OH)D were significantly reduced in patients with HNSCC. We furthermore found disease-free survival, as well as overall survival times to be significantly associated with 25(OH)D levels. In conclusion, results from our study suggest an influence of vitamin D status on cancer incidence, as well as on mortality of HNSCC.

After heart transplantation (HTx), endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. A non-invasive marker of rejection would be desirable as an alternative or to permit more selective use of the costly and invasive EMB.In this retrospective study, outcomes of routinely taken EMBs were used to select 28 patients after HTx EMB Grade 0R (8 patients), 1R (9 patients) or 2R (11 patients). For these patients, myeloperoxidase (MPO) and carbonyl proteins (CP) in serum were measured using enzyme-linked immunoassay (ELISA).MPO and CP levels in post-HTx patients with Grade 2R rejection were significantly (MPO: p0.01; CP: p0.001) elevated at the time of rejection compared with levels 1 month earlier. MPO and CP levels predicted Grade 2R rejection and the best cut-off point was 237.5 μg/l for MPO and 222.5 pmol/mg for CP, respectively. Clinically most important was the marked increase (doubling of basic values within 1 month) of MPO and CP levels in cases of Grade 2R rejection in post-HTx patients.MPO and CP seem to be appropriate parameters to monitor rejection events non-invasively and to minimize the application of EMBs after HTx.

Objective To investigate whether knowledge of fetal outcome influences retrospective interpretation of cardiotocographic tracings and subsequent management recommendations. Design Prospective online study. Setting Seven university hospitals in five European countries. Population Forty-two intrapartum tracings from women with singleton pregnancies and uneventful antepartum courses. Methods Using an online questionnaire, 123 healthcare professionals interpreted 42 tracings without any knowledge of fetal outcome and provided management recommendations according to the National Institute of Clinical Excellence guidelines (intrapartum care). Two months later, 93 of the 123 participants re-interpreted the same re-ordered tracings, this time with information on the newborn's umbilical artery pH. Outcome measures Comparison of the evaluation of tracing features, overall tracing classification, and management recommendations between the initial analysis and re-interpretation. Results In newborns with umbilical artery pH ≤ 7.05, knowledge of the pH value led to significant changes in the evaluation of all basic tracing features. In this group, classification of tracings as ‘normal’ decreased 76% (8.8–2.1%, P < 0.001), whereas classification as ‘pathologic’ increased 51% (44.7–67.5%, P < 0.001). In newborns with pH 7.06–7.19, classification of tracings as ‘normal’ decreased 36% (22.4–14.4%, P < 0.001), and in those with pH ≥ 7.20, classification of tracings as ‘pathologic’ decreased 40% (23.4–14.1%, P < 0.001). In the group of newborns with umbilical artery pH ≤ 7.05, the recommendations ‘no attention needed’ decreased 75% (10.2–2.6%, P < 0.001), and the number of recommendations ‘rapid reversal of hypoxic cause or immediate delivery’ increased 70.3% (42.1–71.7%, P < 0.001). Conclusions When provided with information on adverse fetal outcome, healthcare professionals provide a more pessimistic evaluation of basic tracing features, overall classification, and clinical management recommendations. Tweetable abstract Knowledge of adverse fetal outcome leads to more pessimistic CTG evaluation and management recommendations.

Electronic drug application records from farmers from 75 conventional pig farms were revised and checked for their plausibility. The registered drug amounts were verified by comparing the farmers' records with veterinarians' dispensary records. The antimicrobial consumption was evaluated from 2008 to 2011 and expressed in weight of active substance(s), number of used daily doses (nUDD), number of animal daily doses (nADD) and number of product-related daily doses (nPrDD). All results were referred to one year and animal bodyweight (kg biomass). The data plausibility proof revealed about 14 per cent of unrealistic drug amount entries in the farmers' records. The annual antimicrobial consumption was 33.9 mg/kg/year, 4.9 UDDkg/kg/year, 1.9 ADDkg/kg/year and 2.5 PrDDkg/kg/year (average). Most of the antimicrobials were applied orally (86 per cent) and at group-level. Main therapy indications were metaphylactic/prophylactic measures (farrow-to-finish and fattening farms) or digestive tract diseases (breeding farms). The proportion of the ‘highest priority critically important antimicrobials’ was low (12 per cent). After determination of a threshold value, farms with a high antimicrobial use could be detected. Statistical tests showed that the veterinarian had an influence on the dosage, the therapy indication and the active substance. Orally administered antimicrobials were mostly underdosed, parenterally administered antimicrobials rather correctly or overdosed.

The etiopathogenesis of polymorphic light eruption (PLE) has been linked to impaired UV-immunosuppression, Langerhans cell (LC) retention, and an absence of neutrophil infiltration into UV-exposed PLE skin. We have previously shown that photohardening restores the impaired neutrophil responsiveness to the chemoattractants leucotriene B4 and formyl-methionyl-leucyl-phenylalanin in PLE patients. The aim of this study was to investigate whether photohardening modulates baseline chemokine and cytokine levels which would alter chemoresponsiveness and hence immune function in PLE patients. Sixteen PLE patients received photohardening therapy for 4–9 weeks by 311 nm UVB. Plasma samples were taken both before and within 48 h of the penultimate phototherapeutic exposure. Plasma from these 16 patients, 8 non-irradiated PLE patients, and 14 control subjects was analyzed for IL-1β, CXCL8 (IL-8), IL-10, IL-17, TNF, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), and CCL22 (MDC). These cytokines and chemokines were measured in early spring (March to April) and again in late spring (April to June). PLE patients had a significantly elevated level of CCL11 (p = 0.003) and IL-1β (p = 0.002) in early spring (before phototherapy). In late spring, after phototherapy, PLE patients had significantly elevated CCL2 (p = 0.002) and TNF (p = 0.002) but a trend for lowered plasma levels of CXCL8 (p = 0.021). When comparing the cytokine shifts from early to late spring, while healthy controls and non-UV-irradiated PLE patients showed an increase, PLE patients undergoing photohardening exhibited a trend for decrease in IL-1β (p = 0.012). Taken together, our results indicate that photohardening may alter the complex cytokine milieu in PLE, in particular via IL-1β, helping to normalise the pathophysiologic response to subsequent UV exposure.

PURPOSE Uveitis is a major cause for visual impairment. Inflammation-related gene polymorphisms have previously been shown to confer susceptibility to different types of uveitis. Recently, IL-2 receptor alpha (IL2RA, also called CD25) and IL-7 receptor alpha (IL7RA) gene variants (rs2104286, rs12722489, and rs6897932) have been identified to play an essential role in the pathogenesis of immune-mediated diseases. Their role in uveitis, however, has not yet been studied. The present study was set to investigate a hypothesized association of these gene polymorphisms and the presence of either intermediate or HLA-B27-associated acute anterior uveitis. METHODS One hundred forty-five patients with HLA-B27-associated acute anterior uveitis (AAU), 84 patients with intermediate uveitis, 132 HLA-B27-negative controls, and 61 HLA-B27-positive controls were enrolled. Determination of genotypes was done by polymerase chain reaction. RESULTS The frequency of carriers of the minor allele for rs2104286 was significantly lower in patients with intermediate uveitis compared with HLA-B27 positive and negative controls combined (P = 0.006). Frequencies of the minor allele for rs2104286 did not differ significantly in patients with HLA-B27-associated uveitis (28.3%) when compared with HLA-B27-negative controls (24.2%; P = 0.29) and HLA-B27-positive controls (30.3%; P = 0.72). The rs12722489 and rs6897932 polymorphisms were not significantly associated with either investigated uveitis entity (P > 0.005). CONCLUSIONS These findings suggest an association of the rs2104286 polymorphism with intermediate uveitis, but not with HLA-B27-associated acute anterior uveitis. Because this polymorphism was associated with multiple sclerosis in previous studies, the authors suggest possible parallel pathways between multiple sclerosis and intermediate uveitis but not HLA-B27-associated uveitis.

Cytotoxicity screening is a common technique in drug compound screening for the identification of adverse cellular effects. Nanoparticles may cause interference in these assays. For the interpretation of cytotoxicity data it is important to study also the influence of other factors like pre-treatment of the nanoparticles, the choice of the cell culture medium and type of cell used for testing. Carboxyl polystyrene particles (CPS, 20-1000 nm) were physicochemically characterized and cytotoxicity assessed with seven screening assays in 20 cell lines, which differed in species, growth pattern, cell size, doubling time, embryonic origin and capacity for phagocytosis. Small CPS acted more cytotoxic in all cell lines, larger CPS only in phagocytic cells. Small differences in cytotoxicity were noted between the screening assays. Growth pattern and cell size determined cytotoxicity more than proliferation rate and embryonic origin of cells. Non-adherent cells, cells of mesenchymal origin and with high proliferation rate may be more susceptible to damage by nanoparticles.