Density and proximity of oil and gas wells and concentrations of trace elements in urine, hair, nails and tap water samples from pregnant individuals living in Northeastern British Columbia.

BACKGROUND: Oil and gas exploitation can release several contaminants in the environment, including trace elements, with potentially deleterious effects on exposed pregnant individuals and their developing fetus. Currently, there is limited data on pregnant individuals' exposure to contaminants associated with oil and gas activity. OBJECTIVES: We aimed to 1)measure concentrations of trace elements in biological and tap water samples collected from pregnant individuals participating in the EXPERIVA study; 2)compare with reference populations and health-based guidance values; 3)assess correlations across matrices; and 4)evaluate associations with the density/proximity of oil and gas wells. METHODS: We collected tap water, hair, nails, and repeated urine samples from 85pregnant individuals, and measured concentrations of 21trace elements. We calculated oil and gas well density/proximity (Inverse Distance Weighting [IDW]) for 4buffer sizes (2.5 km, 5 km, 10 km, no buffer). We performed Spearman's rank correlation analyses to assess the correlations across elements and matrices. We used multiple linear regression models to evaluate the associations between IDWs and concentrations. RESULTS: Some study participants had urinary trace element concentrations exceeding the 95th percentile of reference values; 75% of participants for V, 29% for Co, 22% for Ba, and 20% for Mn. For a given trace element, correlation coefficients ranged from -0.23 to 0.65 across matrices; correlations with tap water concentrations were strongest for hair, followed by nails, and urine. Positive (e.g., Cu, Cr, Sr, U, Ga, Ba, Al, Cd) and negative (e.g., Fe) associations were observed between IDW metrics and the concentrations of certain trace elements in water, hair, and nails. SIGNIFICANCE: Our results suggest that pregnant individuals living in an area of oil and gas activity may be more exposed to certain trace elements (e.g., Mn, Sr, Co, Ba) than the general population. Association with density/proximity of wells remains unclear.

Pituitary Metastases From Differentiated Thyroid Cancers: A Systematic Review.

Background: Pituitary metastasis (PM) from differentiated thyroid cancer (DTC) is extremely rare and may adversely affect outcomes. We aimed to assess the characteristics and outcomes of patients with PM from DTC. Methods: We systematically reviewed the literature on publications on PM and the different DTC histologic types (papillary, follicular, and Hurthle cell cancers). Three databases (PubMed, Embase, and Scopus) were searched for articles published from 1967 to 2022. Survival time was estimated as the period from the first treatment of PM to the time of death or last follow-up. Results: Twenty-five articles comprising 27 cases that met the eligibility criteria were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The median age of the patients was 60 years (23 - 86). A preponderance of females (66.7%) with PM most commonly reported papillary thyroid cancer (55.6%). This was followed by follicular thyroid cancer (37.0%) and Hurthle cell cancer (7.4%). The most common presentations were headache, nausea, and vomiting, with visual symptoms in 44.4%. Diabetes insipidus was an infrequent finding (7.4%). The median time from diagnosis or first treatment of DTC to the diagnosis of PM was 3 years (0 - 25). The most common endocrine abnormality was hyperprolactinemia (63.2%), while the most frequently deficient hormone was luteinizing hormone (50%). The most common treatment modality for PM was a combination of radiotherapy and surgery with or without radio-iodine. At the end of the follow-up, 30% of the patients died. Only 33.3% of the patients achieved complete resolution of symptoms. The overall median survival time was 12 months (3 - 108). There was a moderate inverse correlation between the age of patients and survival, which was, however, not statistically significant (rs = -0.45, P = 0.103). Conclusion: PM from DTC is extremely rare, and Hurtle cell cancer appears to be the least associated with PM. Diabetes insipidus is a rare initial manifestation of PM from DTC. Complete resolution of symptoms is less likely to be achieved in PM from DTC. Older age may confer an increased survival tendency, probably due to more intracranial space volume in older people compared to the younger population. Larger studies are needed to examine the relationship between age and survival in PM from DTC. Also, more observational data are required to determine the predictors of survival and compare the efficacy of the different treatment modalities in patients with PM from DTC.

Assessing gestational exposure to trace elements in an area of unconventional oil and gas activity: comparison with reference populations and evaluation of variability.

BACKGROUND: Located in Northeastern British Columbia, the Montney formation is an important area of unconventional oil and gas exploitation, which can release contaminants like trace elements. Gestational exposure to these contaminants may lead to deleterious developmental effects. OBJECTIVES: Our study aimed to (1) assess gestational exposure to trace elements in women living in this region through repeated urinary measurements; (2) compare urinary concentrations to those from North American reference populations; (3) compare urinary concentrations between Indigenous and non-Indigenous participants; and (4) evaluate inter- and intra-individual variability in urinary levels. METHODS: Eighty-five pregnant women participating in the Exposures in the Peace River Valley (EXPERIVA) study provided daily spot urine samples over 7 consecutive days. Samples were analyzed for 20 trace elements using inductively-coupled mass spectrometry (ICP-MS). Descriptive statistics were calculated, and inter- and intra-individual variability in urinary levels was evaluated through intraclass correlation coefficient (ICC) calculation for each trace element. RESULTS: When compared with those from North American reference populations, median urinary levels were higher in our population for barium (~2 times), cobalt (~3 times) and strontium (~2 times). The 95th percentile of reference populations was exceeded at least 1 time by a substantial percentage of participants during the sampling week for barium (58%), cobalt (73%), copper (29%), manganese (28%), selenium (38%), strontium (60%) and vanadium (100%). We observed higher urinary manganese concentrations in self-identified Indigenous participants (median: 0.19 µg/g creatinine) compared to non-Indigenous participants (median: 0.15 µg/g of creatinine). ICCs varied from 0.288 to 0.722, indicating poor to moderate reliability depending on the trace element. SIGNIFICANCE: Our results suggest that pregnant women living in this region may be more exposed to certain trace elements (barium, cobalt, copper, manganese, selenium, strontium, and vanadium), and that one urine spot sample could be insufficient to adequately characterize participants' exposure to certain trace elements. IMPACT STATEMENT: Unconventional oil and gas (UOG) is an important industry in the Peace River Valley region (Northeastern British Columbia, Canada). Information on the impacts of this industry is limited, but recent literature emphasizes the risk of environmental contamination. The results presented in this paper highlight that pregnant women living near UOG wells in Northeastern British Columbia may be more exposed to some trace elements known to be related to this industry compared to reference populations. Furthermore, our results based on repeated urinary measurements show that one urine sample may be insufficient to adequately reflect long-term exposure to certain trace elements.

Disease modeling of cardiac arrhythmias using human induced pluripotent stem cells.

INTRODUCTION: Inherited arrhythmias are an uncommon, but malignant family of cardiac diseases that result from genetic abnormalities in the ion channels and/or structural proteins within cardiomyocytes. Given the inherent differences between species and the limited reproducibility of in vitro heterologous cell models, progress in understanding the mechanisms underlying these malignant diseases has always languished far behind the clinical science and need. The ability to study human induced pluripotent stem cells (iPSCs) derived cardiomyocytes promises to change this paradigm as patient cells have the potential to become testing platforms for disease phenotyping or therapeutic discovery. AREAS COVERED: This review will outline methods developed to genetically reprogram adult cells into iPSCs, differentiate iPSCs into ex vivo models of adult cardiac tissue and iPSCs-based progress in exploring the mechanisms underlying pro-arrhythmic disease phenotypes. EXPERT OPINION: Despite being discovered less than 15 years ago, several studies have successfully leveraged iPSCs-derived cardiomyocytes to study malignant arrhythmogenic diseases. These models promise to increase our understanding of the pathophysiology underlying these complex diseases and may identify personalized approaches to treatment.