How do territorial characteristics affect spatial inequalities in the risk of coronary heart disease?

BACKGROUND: Cardiovascular diseases remain the leading cause of death and disabilities worldwide, with coronary heart diseases being the most frequently diagnosed. Their multifactorial etiology involves individual, behavioral and territorial determinants, and thus requires the implementation of multidimensional approaches to assess links between territorial characteristics and the incidence of coronary heart diseases. CONTEXT AND OBJECTIVES: This study was carried out in a densely populated area located in the north of France with multiple sources of pollutants. The aim of this research was therefore to establish complex territorial profiles that have been characterized by the standardized incidence, thereby identifying the influences of determinants that can be related to a beneficial or a deleterious effect on cardiovascular health. METHODS: Forty-four variables related to economic, social, health, environment and services dimensions with an established or suspected impact on cardiovascular health were used to describe the multidimensional characteristics involved in cardiovascular health. RESULTS: Three complex territorial profiles have been highlighted and characterized by the standardized incidence rate (SIR) of coronary heart diseases after adjustment for age and gender. Profile 1 was characterized by an SIR of 0.895 (sd: 0.143) and a higher number of determinants that revealed favorable territorial conditions. Profiles 2 and 3 were characterized by SIRs of respectively 1.225 (sd: 0.242) and 1.119 (sd: 0.273). Territorial characteristics among these profiles of over-incidence were nevertheless dissimilar. Profile 2 revealed higher deprivation, lower vegetation and lower atmospheric pollution, while profile 3 displayed a rather privileged population with contrasted territorial conditions. CONCLUSION: This methodology permitted the characterization of the multidimensional determinants involved in cardiovascular health, whether they have a negative or a positive impact, and could provide stakeholders with a diagnostic tool to implement contextualized public health policies to prevent coronary heart diseases.

Data for the assessment of vulnerability and resilience in the field of environmental health in the north of France.

The integration of multidimensional data is necessary to improve the understanding of environmental and social inequalities in health. The challenge is to define a dataset that provides the most holistic description possible of the territory. This article presents a relevant dataset to characterize the territorial accumulation of health determinants in the second most densely populated region of metropolitan France (Hauts-de-France Region, in the north of France). The multidimensional dataset combines data related to the economic, social, environment, services, health and policy dimensions at fine scale (i.e., each municipality). Data outlining a negative impact on health inequalities (e.g. anthropogenic pressures, socioeconomics factors related to vulnerability, etc.) are considered to be as important as data outlining a positive impact on health inequalities (e.g. natural resources, diversity and economic drive, etc.). The proposed theoretical framework relies on data reuse. Over one hundred variables covering a time frame from 2008 to 2017 were collected from a dozen public and national database providers. The use of official organizations ensured the quality of the collected data. The Geographic Information System, designed to map and catalogue ready-to-use data, was used to generate new data or to deal with missing data. Finally, 50 variables, including mostly quantitative but also qualitative data, were selected after application of inclusion and exclusion criteria. The resulting dataset provides a broad characterisation of the 3,817 municipalities in the Hauts-de-France Region. These data will help to discriminate the distribution pattern of vulnerability and resilience levels in this region. This novel approach is described in the paper "How can we analyse environmental health resilience and vulnerability? A joint analysis with composite indices applied to the north of France", which provides a detailed description of the methodology used to develop composite indices. This research could therefore be of use to researchers, policy makers and stakeholders in the field of environmental health seeking to identify the weaknesses but also the strengths of municipalities.

How can we analyze environmental health resilience and vulnerability? A joint analysis with composite indices applied to the north of France.

In environmental health, vulnerability reflecting the cumulative harmful constraints and nuisances to which populations are subjected and resilience defined as the capacity of a territory to cope with health inequalities have been little extensively investigated together with the same importance. Besides the diversity of factors involved, there is no consensual framework to develop composite indices, one recognized methodology to deal with a multifaceted issue. Therefore, this research aims to establish a new transferable approach to assess the spatial heterogeneity of territorial inequalities. This new strategy relies on the simultaneous evaluation of resilience and vulnerability and the joint analysis based on the cross-interpretation of the spatialized composite indices of resilience and vulnerability. A case study was conducted to demonstrate the feasibility of this methodology, using the municipality as a spatial unit of analysis within a region in the north of France. To provide the most holistic description possible of the 3817 studied municipalities, 50 variables related to the economic, environment, policy, health, services and social dimensions were used to develop the composite indices. The vulnerability Index has a median value of 0.151 with an IQR of [0.126-0.180] and the Resilience Index has a median value of 0.341 with an IQR of [0.273-0.401]. The joint analysis was conducted to classify each municipality among four defined typologies: 1687 municipalities (44.2%) belong to the "To monitor" category, 1646 (43.1%) to the "Resilient" category, 329 (8.6%) to the "Have resources" category and 155 (4.1%) to the "Territorial blackspot" category. The methodology herein may be a diagnostic tool to identify and prioritize municipalities that could benefit from the implementation of specifically tailored public health policies.

Spatial analysis of hypospadias cases in northern France: taking clinical data into account.

BACKGROUND: Strong evidence for a causal role of environmental factors in a congenital anomaly is still difficult to produce. The collection of statistical data is crucial for gaining a better understanding of the epidemiology and pathophysiology of these anomalies. We aimed to evaluate spatial variations in hypospadias within our region and it's association to socioeconomic and ecological factors, taking clinical data into account. METHODS: All boys with hypospadias born in northern France and seen in Lille University Medical Center (Lille, France) between 1999 and 2012 were included in the analysis. We retrospectively collected geographic data, clinical data (especially known confounding factors associated with an elevated risk of hypospadias), and demographic, socio-economic and ecological data. We analyzed the entire study population and subsequently the subset of boys lacking confounding factors. RESULTS: The study sample of 975 cases of hypospadias over the 13-year period resulted in an incidence of 25.4/10,000 male births, and was characterized by significant spatial heterogeneity (p < 0.005) and autocorrelation (p < 0.001). We detected two high-incidence clusters that differed with regard to their land use. After the exclusion of 221 patients with confounding factors, two high-incidence clusters with significant disease risks (1.65 and 1.75, respectively; p < 0.001) and a significant difference in land use (p < 0.001) again appeared. The first cluster contained a higher median [interquartile range] proportion of artificialized land (0.40 [0.22;0.47]) than the remaining "neutral areas" (0.19 [0.08;0.53]) did (p < 0.001). Conversely, the second cluster contained a higher median proportion of rural land (0.90 [0.78;0.96]) than the "neutral areas" (0.81 [0.47;0.92]) did (p < 0.001). The median deprivation index was significantly lower in the urban cluster (0.47 [0.42;0.55]) and significantly higher in the rural cluster (0.69 [0.56;0.73]) (p < 0.001). CONCLUSIONS: Our results evidenced the heterogeneous spatial distribution of cases of hypospadias in northern France. We identified two clusters with different environmental and social patterns - even after the exclusion of known confounding factors.

Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment.

The mutagenic patterns of A. flavus, A. parasiticus and A. fumigatus extracts were evaluated. These strains of toxigenic Aspergillus were collected from the agricultural environment. The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). These data were compared with the mutagenicity of the corresponding pure mycotoxins tested alone or in reconstituted mixtures with equivalent concentrations, in order to investigate the potential interactions between these molecules and/or other natural metabolites. At least 3 mechanisms are involved in the mutagenic response of these aflatoxins: firstly, the formation of AFB1-8,9-epoxide upon addition of S9mix, secondly the likely formation of oxidative damage as indicated by significant responses in TA102, and thirdly, a direct mutagenicity observed for higher doses of some extracts or associated mycotoxins, which does not therefore involve exogenously activated intermediates. Besides the identified mycotoxins (AFB1, AFB2 and AFM1), additional "natural" compounds contribute to the global mutagenicity of the extracts. On the other hand, AFB2 and AFM1 modulate negatively the mutagenicity of AFB1 when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of "natural" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli.

Crohn's disease and environmental contamination: Current challenges and perspectives in exposure evaluation.

Although the incidence of Crohn's disease has increased worldwide over the past 30 years, the disorder's exact causes and physiological mechanisms have yet to be determined. Given that genetic determinants alone do not explain the development of Crohn's disease, there is growing interest in "environmental" determinants. In medical science, the term "environment" refers to both the ecological and social surroundings; however, most published studies have focused on the latter. In environmental and exposure sciences, the term "environment" mostly relates to contamination of the biotope. There are many unanswered questions on how environmental hazards might contribute to the pathogenesis of Crohn's disease. Which pollutants should be considered? Which mechanisms are involved? And how should environmental contamination and exposure be evaluated? The objective was to perform a systematic review of the literature on Crohn's disease and environmental contamination. We searched the PubMed, Google Scholar, Scopus, ISI Web of Science and Prospero databases. We considered all field studies previous to April 2019 conducted on human health indicators, and evaluating exposure to all type of physical, biological and chemical contamination of the environment. The lack of clear answers to date can be ascribed to the small total number of field studies (n = 16 of 39 publications, most of which were conducted by pioneering medical scientists), methodological differences, and the small number of contaminants evaluated. This make it impossible to conduct a coherent and efficient meta-analysis. Based on individual analysis of available studies, we formulated five recommendations on improving future research: (i) follow up the currently identified leads - especially metals and endocrine disruptors; (ii) explore soil contamination; (iii) gain a better knowledge of exposure mechanisms by developing transdisciplinary studies; (iv) identify the most plausible contaminants by developing approaches based on the source-to-target distance; and (v) develop registries and cohort-based analyses.

Exposure to multiple air pollutants and the incidence of coronary heart disease: A fine-scale geographic analysis.

Geographical variations in cardiovascular disease rates have been linked to individual air pollutants. Investigating the relation between cardiovascular disease and exposure to a complex mixture of air pollutants requires holistic approaches. We assessed the relationship between exposure to multiple air pollutants and the incidence of coronary heart disease (CHD) in a general population sample. We collected data in the Lille MONICA registry (2008-2011) on 3268 incident cases (age range: 35-74). Based on 20 indicators, we derived a composite environmental score (SEnv) for cumulative exposure to air pollution. Poisson regression models were used to analyse associations between CHD rates on one hand and SEnv and each single indicator on the other (considered in tertiles, where T3 is the most contaminated). We adjusted models for age, sex, area-level social deprivation, and neighbourhood spatial structure. The incidence of CHD was a spatially heterogeneous (p=0.006). There was a significant positive association between SEnv and CHD incidence (trend p=0.0151). The relative risks [95%CI] of CHD were 1.08 [0.98-1.18] and 1.16 [1.04-1.29] for the 2nd and 3rd tertile of SEnv exposure. In the single pollutant analysis, PM10, NO2, cadmium, copper, nickel, and palladium were significantly associated with CHD rates. Multiple air pollution was associated with an increased risk of CHD. Single pollutants reflecting road traffic pollution were the most strongly associated with CHD. Our present results are consistent with the literature data on the impact of road traffic on the CHD risk in urban areas.

Spatial heterogeneity of KRAS mutations in colorectal cancers in northern France.

BACKGROUND: Somatic mutations in the KRAS gene are the most common oncogenic mutations found in human cancers. However, no clinical features have been linked to KRAS mutations in colorectal cancer [CRC]. PURPOSE: In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France. PATIENTS AND METHODS: All patients with CRC who were identified to have KRAS mutations between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. 2,486 patients underwent a KRAS status available, with 40.9% of CRC with KRAS mutations in northern France. We retrospectively collected demographic and geographic data from these patients. The proportions of KRAS mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models. RESULTS: A mutation at KRAS codon 12 or 13 was found in 1,018 patients [40.9%]. We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant [Cluster 1; proportion of KRAS mutation among CRC: 0.4570; RR=1.29; P=0.0314]. We made an ecological study which did not highlight a significant association between KRAS mutations and the distance to the Closest Waste Incineration Plant, and between KRAS mutations and The French Ecological Deprivation Index but few socio-economic and environmental data were available. CONCLUSION: There was a spatial heterogeneity and a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of KRAS mutations.

The comet assay in higher terrestrial plant model: Review and evolutionary trends.

The comet assay is a sensitive technique for the measurement of DNA damage in individual cells. Although it has been primarily applied to animal cells, its adaptation to higher plant tissues significantly extends the utility of plants for environmental genotoxicity research. The present review focuses on 101 key publications and discusses protocols and evolutionary trends specific to higher plants. General consensus validates the use of the percentage of DNA found in the tail, the alkaline version of the test and root study. The comet protocol has proved its effectiveness and its adaptability for cultivated plant models. Its transposition in wild plants thus appears as a logical evolution. However, certain aspects of the protocol can be improved, namely through the systematic use of positive controls and increasing the number of nuclei read. These optimizations will permit the increase in the performance of this test, namely when interpreting mechanistic and physiological phenomena.

Recurrence of Stachybotrys chartarum during mycological and toxicological study of bioaerosols collected in a dairy cattle shed.

Agricultural occupations associated with animal breeding and the processing of animal materials in confinement systems could potentially lead to bioaerosol exposures. Moulds and mycotoxins could be constituents of bioaerosols and should be studied because of their possible involvement in respiratory diseases and cancers. In order to characterize the fungal contamination of the indoor air in a dairy barn, bioaerosols were collected during 20 days in a cattle farm located in Normandy (France). Mycobiota, mycotoxins and the mutagenicity of bioaerosols were studied. The toxigenic ability of Aspergillus flavus group and Aspergillus fumigatus isolates was also evaluated in vitro. The prevalent airborne moulds were from the following potentially toxigenic species: Aspergillus flavus group, Aspergillus fumigatus, Penicillium chrysogenum, Stachybotrys chartarum, and the allergenic species Ulocladium chartarum, Cladosporium cladosporioides. In comparison with harvesting, grain handling or broiler breeding, the concentrations of viable moulds were lower in the cattle shed. Seasonal variations in levels of several species were also observed. This study revealed that aflatoxins were detected in bioaerosols and, for the first time, showed that farmers are possibly exposed to Stachybotrys chartarum during routine barn work. Moreover, the finding of mutagenicity from bioaerosols needs further investigations on bioaerosol composition.

How to improve the hygienic quality of forages for horse feeding.

BACKGROUND: Improving the hygienic quality of forages for horse nutrition seems to be a reasonable target for decreasing the prevalence of pulmonary diseases. The aim of the experiment was to study the effects of different agricultural practices on the main aero-allergens contained in forages, including breathable dust, fungi, mycotoxins and pollens. RESULTS: Results showed that the late harvest of hay, a second crop or a haylage production provides a good alternative to increase hygienic quality by reducing fungi contamination and breathable dust content. Barn drying of hay, while having no effect on breathable dust, similarly reduced fungi contamination. In contrast, when hay was harvested at a lower dry mass content (750 g DM kg⁻¹ versus 850 g DM kg⁻¹), both breathable dust and fungi contaminations were increased, which could at least be reversed by adding propionic acid just before baling. Zearalenone was detected in different hays, and even in one case, in breathable dust. CONCLUSION: Overall, our data suggest that different approaches can be used to increase forage hygienic quality for horse feeding and thus reduce their exposure to factors involved in equine pulmonary disease.

Mycoflora and mycotoxin production in oilseed cakes during farm storage.

Agricultural activities involve the use of oilseed cakes as a source of proteins for livestock. Because the storage of oilseed cakes could induce the development of molds and the production of mycotoxins, a survey was conducted during the 5 months of farm storage. Mycoflora was studied by microscopic examinations, and the presence of Aspergillus fumigatus was confirmed by polymerase chain reaction. A multimycotoxin method was developed to quantify seven mycotoxins (aflatoxin B(1), alternariol, fumonisin B(1), gliotoxin, ochratoxin A, T-2 toxin, and zearalenone) in oilseed cakes by high-performance liquid chromatography coupled to mass spectrometry. Among 34 fungal species identified, A. fumigatus and Aspergillus repens were observed during 5 and 4 months, respectively. Gliotoxin, an immunosuppressive mycotoxin, was quantified in oilseed cakes up to 45 microg/kg, which was associated with the presence of toxigenic isolates of A. fumigatus.