Total invasion of the pancreatic gland by a rare aggressive IPMN: Report of a case

AbstractINTRODUCTIONThe intraductal papillary mucinous neoplasms (IPMNs) are increasingly diagnosed entities with high potential of malignancy and significant recurrence rates.PRESENTATION OF CASEIn this case report a rare mixed IPMN with full invasion of the pancreatic ducts was identified.DISCUSSIONDifficulties in determining the grade of pancreatic duct involvement make the surgical management tough.CONCLUSIONIn multifocal IPMNs the management of the patients is even more challenging. In this case the patient was treated successfully with total pancreatectomy

A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11–12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value < 0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value < 0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value < 0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (β = -0.131; [95% CI: 0.179, -0.920], Q-value < 0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children’s exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children’s age- and-sex-standardized BMI z-scores, but causal inferences regarding organic diet’s physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial

Oral Ingestion of Hexavalent Chromium through Drinking Water and Cancer Mortality in an Industrial Area of Greece - An Ecological Study

Background: Hexavalent chromium is a known carcinogen when inhaled, but its carcinogenic potential when orally ingested remains controversial. Water contaminated with hexavalent chromium is a worldwide problem, making this a question of significant public health importance. Methods: We conducted an ecological mortality study within the Oinofita region of Greece, where water has been contaminated with hexavalent chromium. We calculated gender, age, and period standardized mortality ratios (SMRs) for all deaths, cancer deaths, and specific cancer types of Oinofita residents over an 11-year period (1999 - 2009), using the greater prefecture of Voiotia as the standard population. Results: A total of 474 deaths were observed. The SMR for all cause mortality was 98 (95% CI 89-107) and for all cancer mortality 114 (95% CI 94-136). The SMR for primary liver cancer was 1104 (95% CI 405-2403, p-value < 0.001). Furthermore, statistically significantly higher SMRs were identified for lung cancer (SMR = 145, 95% CI 100-203, p-value = 0.047) and cancer of the kidney and other genitourinary organs among women (SMR = 368, 95% CI 119-858, p-value = 0.025). Elevated SMRs for several other cancers were also noted (lip, oral cavity and pharynx 344, stomach 121, female breast 134, prostate 128, and leukaemias 168), but these did not reach statistical significance. Conclusions: Elevated cancer mortality in the Oinofita area of Greece supports the hypothesis of hexavalent chromium carcinogenicity via the oral ingestion pathway of exposure. Further studies are needed to determine whether this association is causal, and to establish preventive guidelines and public health recommendations

Analytical performance specifications for 25-hydroxyvitamin d examinations

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1–5 and 6–10, did not allow for correction of the lack of homogene-ity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supple-mentation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appro-priate

Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain regions: the hypothalamus and white-matter tissue. In addition, a potential association between these npEDCs concentrations and obesity was investigated. Post-mortem brain material was obtained from 24 individuals, made up of 12 obese and 12 normal-weight subjects (defined as body mass index (BMI) > 30 and BMI < 25 kg/m2, respectively). Nine phenols and seven parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross the blood–brain barrier. Whether the presence of npEDCs can adversely affect brain function and to which extent the detected concentrations are physiologically relevant needs to be further investigated.Jana V. van Vliet-Ostaptchouk is supported by a Diabetes Funds Junior Fellowship from the Dutch Diabetes Research Foundation (project no. 2013.81.1673). This work was supported by the National Consortium for Healthy Ageing (NCHA) (NCHA NGI Grant 050-060-810), and the European Union’s Seventh Framework program (FP7/2007-2013) through the BioSHaRE-EU (Biobank Standardization and Harmonization for Research Excellence in the European Union) project, grant agreement 261433, and by the Danish Center on Endocrine Disrupters and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC)

Analytical performance specifications for the measurement uncertainty of 24,25-dihydroxyvitamin D examinations

Objectives: The exploration of the metabolites in the degradation pathways of vitamin D (VTD) has gained importance in recent years and simultaneous quantitation of twenty-five-hydroxy vitamin D (25(OH)D) mass concentration together with 24,25-dihydroxyvitamin D (24,25(OH)2D) has been proposed as a newer approach to define VTD deficiency. Yet, no data are available on 24,25(OH)2D biological variation (BV). In this study, we evaluated 24,25(OH)2D's BV on the European Biological Variation Study (EuBIVAS) cohort samples to determine if analytical performance specifications (APS) for 24,25(OH)2D could be generated. Methods: Six European laboratories recruited 91 healthy participants. 25(OH)D and 24,25(OH)2D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate with a validated LC-MS/MS method. The Vitamin D Metabolite Ratio (24,25(OH)2D divided by 25(OH)D × 100) was also calculated at each time point. Results: Linear regression of the mean 24,25(OH)2D concentrations at each blood collection showed participants were not in steady state. Variations of 24,25(OH)2D over time were significantly positively associated with the slopes of 25(OH)D concentrations over time and the concentration of 25(OH)D of the participant at inclusion, and negatively associated with body mass index (BMI), but not with age, gender, or location of the participant. The variation of the 24,25(OH)2D concentration in participants over a 10 weeks period was 34.6%. Methods that would detect a significant change linked to the natural production of 24,25(OH)2D over this period at p&lt;0.05 would need a relative measurement uncertainty (u%)&lt;14.9% while at p&lt;0.01, relative measurement uncertainty should be &lt;10.5%. Conclusions: We have defined for the first time APS for 24,25(OH)2D examinations. According to the growing interest in this metabolite, several laboratories and manufacturers might aim to develop specific methods for its determination. The results presented in this paper are thus necessary prerequisites for the validation of such methods.</p

Application of the urban exposome framework using drinking water and quality of life indicators: a proof-of-concept study in Limassol, Cyprus

Background Cities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome concept refers to the continuous monitoring of urban environmental and health indicators using the city and smaller intra-city areas as measurement units in an interdisciplinary approach that combines qualitative and quantitative methods from social sciences, to epidemiology and exposure assessment. Methods In this proof of concept study, drinking water and quality of life indicators were described as part of the development of the urban exposome of Limassol (Cyprus) and were combined with agnostic environment-wide association analysis. This study was conducted as a two-part project with a qualitative part assessing the perceptions of city stakeholders, and quantitative part using a cross-sectional study design (an urban population study). We mapped the water quality parameters and participants’ opinions on city life (i.e., neighborhood life, health care, and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory, agnostic, environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them. Results Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes (THM)) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (false discovery rate corrected p-value < 0.1) associated with different health conditions such as hypertension and asthma, as well as having financial issues in access to dental care. Additionally, correlations between THM exposures and participant behavioral characteristics (e.g., household cleaning, drinking water habits) were documented. Conclusion This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differences in environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics

A preliminary assessment of low level arsenic exposure and diabetes mellitus in Cyprus

<p>Abstract</p> <p>Background</p> <p>A preliminary study was undertaken in a community of Cyprus where low-level arsenic (As) concentrations were recently detected in the groundwater that was chronically used to satisfy potable needs of the community. The main objective of the study was to assess the degree of association between orally-ingested As and self-reported type-2 diabetes mellitus (DM) in 317 adult (≥18 years old) volunteers.</p> <p>Methods</p> <p>Cumulative lifetime As exposure (CLAEX) (mg As) was calculated using the median As concentrations in water, individual reported daily water consumption rates, and lifetime exposure duration. Logistic regression models were used to model the probability of self-reported DM and calculate odds ratios (OR) in univariate and multivariate models.</p> <p>Results</p> <p>Significantly higher (p <it><</it> 0.02) CLAEX values were reported for the diabetics (median = 999 mg As) versus non-diabetics (median = 573 mg As), suggesting that As exposure could perhaps be related to the prevalence of DM in the study area, which was 6.6%. The OR for DM, comparing participants in the 80^th versus the 20^th percentiles of low-level As CLAEX index values, was 5.0 (1.03, 24.17), but after adjusting for age, sex, smoking, education, and fish consumption, the As exposure effect on DM was not significant.</p> <p>Conclusions</p> <p>Further research is needed to improve As exposure assessment for the entire Cypriot population while assessing the exact relationship between low-level As exposure and DM.</p

Biomonitoraggio umano come strumento per valutare l’esposizione nei siti industriali contaminati. Lezioni apprese dal network europeo icshnet

BACKGROUND: the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. OBJECTIVES: to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. METHODS: based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. RESULTS: all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of ex posure, which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakehold ers throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. CONCLUSIONS: based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers

EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.publishersversionpublishe