Mental health and neurocognitive disorder-related hospitalization rates in immigrants and Canadian-born population: a linkage study.

OBJECTIVES: Mental health and neurocognitive conditions are important causes of hospitalization among immigrants, though patterns may vary by immigrant category, world region of origin, and time since arrival in Canada. This study uses linked administrative data to explore differences in mental health hospitalization rates between immigrants and individuals born in Canada. METHODS: Hospital records from the Discharge Abstract Database and the Ontario Mental Health Reporting System for 2011 to 2017 were linked to the 2016 Longitudinal Immigrant Database and to Statistics Canada's 2011 Canadian Census Health and Environment Cohort. Age-standardized hospitalization rates for mental health-related conditions (ASHR-MHs) were derived for immigrants and the Canadian-born population. ASHR-MHs overall and for leading mental health conditions were compared between immigrants and the Canadian-born population, stratified by sex and selected immigration characteristics. Quebec hospitalization data were not available. RESULTS: Overall, immigrants had lower ASHR-MHs compared to the Canadian-born population. Mood disorders were leading causes of mental health hospitalization for both cohorts. Psychotic, substance-related, and neurocognitive disorders were also leading causes of mental health hospitalization, although there was variation in their relative importance between subgroups. Among immigrants, ASHR-MHs were higher among refugees and lower among economic immigrants, those from East Asia, and those who arrived in Canada most recently. CONCLUSION: Differences in hospitalization rates among immigrants from various immigration streams and world regions, particularly for specific types of mental health conditions, highlight the importance of future research that incorporates both inpatient and outpatient mental health services to further understand these relationships.

RéSUMé: OBJECTIFS: Les problèmes de santé mentale et les troubles neurocognitifs sont des causes importantes d'hospitalisation chez les immigrants, bien que les tendances puissent varier selon la catégorie d'immigrants, la région d'origine mondiale et le temps écoulé depuis l'arrivée au Canada. Cette étude utilise des données administratives couplées afin d'explorer les différences dans les taux d'hospitalisation en santé mentale entre les immigrants et les personnes nées au Canada. MéTHODES: Les dossiers hospitaliers de la Base de données sur les congés des patients et du Système d'information ontarien sur la santé mentale de 2011 à 2017 ont été couplés à la Base de données longitudinales sur l'immigration de 2016 et aux cohortes santé et environnement du Recensement canadien de 2011 de Statistique Canada. Les taux d'hospitalisation normalisés selon l'âge pour les problèmes de santé mentale (THNA-SM) ont été comparés entre les immigrants et la population née au Canada, stratifiés selon le sexe et certaines caractéristiques d'immigration. Les données sur les hospitalisations au Québec n'étaient pas disponibles. RéSULTATS: Dans l'ensemble, les immigrants avaient des THNA-SM plus faibles que la population née au Canada. Les troubles de l'humeur étaient les principales causes d'hospitalisation en santé mentale pour les deux cohortes. Les troubles psychotiques, liés aux substances et neurocognitifs étaient également les principales causes d'hospitalisation en santé mentale, bien que leur importance relative varie entre les sous-groupes. Chez les immigrants, les THNA-SM étaient plus élevés chez les réfugiés et plus faibles chez les immigrants économiques, ceux de l'Asie de l'Est et ceux qui sont arrivés au Canada plus récemment. CONCLUSION: Les différences dans les taux d'hospitalisation chez les immigrants des divers groupes d'immigration et régions du monde, plus particulièrement pour certains types de problèmes de santé mentale, soulignent l'importance de recherches futures qui intègrent les services de santé mentale aux patients hospitalisés ainsi qu'aux patients externes afin de mieux comprendre ces relations.

Development of an estrogen-dependent breast cancer co-culture model as a tool for studying endocrine disruptors.

We developed an innovative co-culture system composed of Hs578t human mammary stromal-like cells and T47D hormone-dependent breast epithelial tumor cells as a representative in vitro model of the human hormone-dependent mammary tumor microenvironment. Hs578t cells expressed aromatase (CYP19) mainly via the healthy stromal CYP19 promoter I.4, but also to a lesser extent via the breast cancer-relevant promoters PII, I.3 and I.7, and produced estrogens from androgen precursors. These estrogens stimulated T47D cell proliferation and estrogen receptor-dependent expression of trefoil factor-1 (TFF1), which is known to stimulate mammary tumor cell proliferation and migration. Hs578t cells can also undergo a "promoter-switch" where the normally silent CYP19 promoters PII, I.3 and I.7 become activated, which mimics the in vivo situation in human breast cancer patients. This positive feedback loop is the hallmark of the hormone-dependent breast tumor microenvironment. Using the co-culture model we designed, we evaluated the promoter-specific expression of CYP19, expression of estrogen-dependent gene TFF1, and determined the effects exhibited by basil and fennel seed essential oils on steroidogenesis in the tumor microenvironment.

Effects of Neonicotinoid Pesticides on Promoter-Specific Aromatase (CYP19) Expression in Hs578t Breast Cancer Cells and the Role of the VEGF Pathway.

BACKGROUND: Aromatase (CYP19) is a key enzyme in estrogens biosynthesis. In the mammary gland, CYP19 gene is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, fibroblast cells surrounding the tumor express increased levels of CYP19 mRNA due to a decrease of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter activity. Little is known about the effects of environmental chemicals on the promoter-specific CYP19 expression. OBJECTIVE: We aimed to determine the effects of two neonicotinoids (thiacloprid and imidacloprid) on promoter-specific CYP19 expression in Hs578t breast cancer cells and understand the signaling pathways involved. METHODS: Hs578t cells were exposed to various signaling pathway stimulants or neonicotinoids for 24 h. Promoter-specific expression of CYP19 was determined by real-time quantitative polymerase chain reaction and catalytic activity of aromatase by tritiated water release assay. RESULTS: To our knowledge, we are the first to demonstrate that the normal I.4 promoter and the breast cancer-relevant PII, I.3, and I.7 promoters of CYP19 are active in these cells. We found that the expression of CYP19 via promoters PII, I.3, and I.7 in Hs578t cells was, in part, dependent on the activation of two VEGF signaling pathways: mitogen-activated protein kinase (MAPK) 1/3 and phospholipase C (PLC). Exposure of Hs578t cells to environmental concentrations of imidacloprid and thiacloprid resulted in a switch in CYP19 promoter usage, involving inhibition of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter-mediated CYP19 expression and aromatase catalytic activity. Greater effects were seen at lower concentrations. Our results suggest that thiacloprid and imidacloprid exert their effects at least partially by inducing the MAPK 1/3 and/or PLC pathways. CONCLUSIONS: We demonstrated in vitro that neonicotinoids may stimulate a change in CYP19 promoter usage similar to that observed in patients with hormone-dependent breast cancer. https://doi.org/10.1289/EHP2698.

The use of a unique co-culture model of fetoplacental steroidogenesis as a screening tool for endocrine disruptors: The effects of neonicotinoids on aromatase activity and hormone production.

Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid. Aromatase catalytic activity was determined in both cell lines using the tritiated water-release assay. Hormone production was measured by ELISA. The three neonicotinoids induced aromatase activity in our fetoplacental co-culture and concordingly, estradiol and estrone production were increased. In contrast, estriol production was strongly inhibited by the neonicotinoids. All three pesticides induced the expression of CYP3A7 in H295R cells, and this induction was reversed by co-treatment of H295R cells with exogenous estriol. CYP3A7 is normally expressed in fetal liver and is a key enzyme involved in estriol synthesis. We suggest that neonicotinoids are metabolized by CYP3A7, thus impeding the 16α-hydroxylation of fetal DHEA(-sulfate), which is normally converted to estriol by placental aromatase. We successfully used the fetoplacental co-culture as a physiologically relevant tool to highlight the potential effects of neonicotinoids on estrogen production, aromatase activity and CYP3A7 expression during pregnancy.