Targeted biomonitoring studies quantifying the concentration of zeranols in biological matrices have focused on liquid chromatography interfaced to mass spectrometry (LC–MS). The MS platform for ...measurement, quadrupole, time-of-flight (ToF), ion trap, etc., is often chosen based on either sensitivity or selectivity. An instrument performance comparison of the benefits and limitations using matrix-matched standards containing 6 zeranols on 4 MS instruments, 2 low-resolution (linear ion traps), and 2 high-resolution (Orbitrap and ToF) was undertaken to identify the best measurement platform for multiple biomonitoring projects characterizing the endocrine disruptive properties of zeranols. Analytical figures of merit were calculated for each analyte to compare instrument performance across platforms. The calibration curves had correlation coefficients
r
= 0.989 ± 0.012 for all analytes and LODs and LOQs were ranked for sensitivity: Orbitrap > LTQ > LTQXL > G1 (V mode) > G1 (W mode). The Orbitrap had the smallest measured variation (lowest %CV), while the G1 had the highest. Instrumental selectivity was calculated using full width at half maximum (FWHM) and as expected, the low-resolution instruments had the broadest spectrometric peaks, concealing coeluting peaks under the same mass window as the analyte. Multiple peaks from concomitant ions, unresolved at low resolution (within a unit mass window), were present but did not match the exact mass predicted for the analyte. For example, the high-resolution platforms were able to differentiate between a concomitant peak at 319.1915 from the analyte at 319.1551, included in low-resolution quantitative analyses demonstrating the need to consider coeluting interfering ions in biomonitoring studies. Finally, a validated method using the Orbitrap was applied to human urine samples from a pilot cohort study.
Background
Stage III renal cell carcinoma (RCC) encompasses both lymph node‐positive (pT1‐3N1M0) and lymph node–negative (pT3N0M0) disease. However, prior institutional studies have indicated that ...among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer.
Methods
Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node‐positive stage III (pT1‐3N1M0), lymph node–negative stage III (pT3N0M0), or stage IV metastatic (pT1‐3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan‐Meier estimates illustrated relative survival when comparing staging groups.
Results
A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node–negative stage III disease, 2218 as having lymph node‐positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node–negative stage III disease, but similar survival was noted between patients with lymph node‐positive stage III and stage IV RCC, with 5‐year survival rates of 61.9% (95% confidence interval 95% CI, 60.3%‐63.4%), 22.7% (95% CI, 20.6%‐24.9%), and 15.6% (95% CI, 11.1%‐23.8%), respectively.
Conclusions
Current RCC staging systems group pT1‐3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1‐3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.
The findings of the current study indicate that patients with lymph node‐positive, American Joint Committee on Cancer stage III kidney cancer have survival outcomes that are more similar to those of patients with stage IV disease than their counterparts with stage III disease with no lymph node involvement. Thus, the current study not only validates prior smaller institutional studies but also provides further evidence that patients with lymph node involvement should be considered as having stage IV kidney cancer.
•First epidemiological study assessing metals and prenatal sex-steroid hormones.•Windows of exposure are important for metals endocrine disruption potential.•CRH is a possible mechanism by which ...endocrine disruptors impact pregnancy.•Essential metals may be contributors of adverse maternal and fetal outcomes.
Metal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes.
Pregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations.
Arsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4–39.6) and decreased levels in testosterone (%Δ: −16.3, 95%CI: −26.2-−5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3–4.2), E3 (%Δ range: 3.9–8.7) and progesterone (%Δ range: 4.1–6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ −13.3, 95%CI: −18.7-−7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01).
Our analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.
Claustrophobia remains a challenging barrier for a significant number of patients to successfully complete a Magnetic Resonance Imaging (MRI) examination. While use of wide-bore machines and pre-exam ...administration of a low-dose benzodiazepine are commonly employed, there is little published research to determine which modality is the most efficacious based on the patient's specific degree of claustrophobia. This retrospective case-control study examines the efficacy of using a low-dose oral benzodiazepine and wide-bore magnet to successfully aid the claustrophobic patient in completing an MRI Brain examination.
3966 non-contrast MRI brain examinations were considered for this study. The sample was filtered to include only patients who were older than 18 years of age, not currently experiencing symptoms which may hinder MRI examination, and did not undergo any additional MR studies at the time of their exam, resulting in a final sample of 2358 examinations for analysis. Patients were then sub-divided based on severity of claustrophobia and analyzed using logistic regression analysis.
Use of wide-bore magnet increased odds of successfully completing the MRI Brain examination in mild, moderately, and severely claustrophobic patients (OR: 1.79, 95% CI: 1.17–2.75). The administration of pre-examination low-dose oral benzodiazepine increased odds of successfully completing the MRI Brain examination in severely claustrophobic patients (OR: 6.21, 95% CI: 1.63–19.28).
Use of a wide-bore magnet is effective in assisting mild, moderately, and severely claustrophobic patients in completing an MRI Brain exam. However, the efficacy of low-dose oral benzodiazepine is limited to severely claustrophobic patients.
•Wide-bore MRI machines are useful for patients suffering all degrees of claustrophobia.•Efficacy of oral anxiolytics in MRI Brain exams is limited to severely claustrophobic patients.•Further prospective analysis of other claustrophobia-reducing modalities is suggested.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals found in drinking water and consumer products, resulting in ubiquitous human exposure. PFAS have been linked to endocrine disruption ...and altered weight gain across the lifespan. A limited and inconsistent body of research suggests PFAS may impact gestational weight gain (GWG) and postpartum body mass index (BMI), which are important predictors of overall infant and maternal health, respectively.
In the Understanding Pregnancy Signals and Infant Development (UPSIDE/UPSIDE-MOMs) study (n = 243; Rochester, NY), we examined second trimester serum PFAS (PFOS: perfluorooctanesulfonic acid, PFOA: perfluorooctanoic acid, PFNA: perfluorononanoic acid, PFHxS: perfluorohexanesulfonic acid, PFDA: perfluorodecanoic acid) in relation to GWG (kg, and weekly rate of gain) and in the postpartum, weight retention (PPWR (kg) and total body fat percentage (measured by bioelectrical impedance)). We fit multivariable linear regression models examining these outcomes in relation to log-transformed PFAS in the whole cohort as well as stratified by maternal pre-pregnancy BMI (< 25 vs. = > 25 kg/m
), adjusting for demographics and lifestyle factors. We used weighted quantile sum regression to find the combined influence of the 5 PFAS on GWG, PPWR, and body fat percentage.
PFOA and PFHxS were inversely associated with total GWG (PFOA: ß = -1.54 kg, 95%CI: -2.79, -0.30; rate ß = -0.05 kg/week, 95%CI: -0.09, -0.01; PFHxS: ß = -1.59 kg, 95%CI: -3.39, 0.21; rate ß = -0.05 kg/week, 95%CI: -0.11, 0.01) and PPWR at 6 and 12 months (PFOA 6 months: ß = -2.39 kg, 95%CI: -4.17, -0.61; 12 months: ß = -4.02 kg, 95%CI: -6.58, -1.46; PFHxS 6 months: ß = -2.94 kg, 95%CI: -5.52, -0.35; 12 months: ß = -5.13 kg, 95%CI: -8.34, -1.93). PFOA was additionally associated with lower body fat percentage at 6 and 12 months (ß = -1.75, 95%CI: -3.17, -0.32; ß = -1.64, 95%CI: -3.43, 0.16, respectively) with stronger associations observed in participants with higher pre-pregnancy BMI. The PFAS mixture was inversely associated with weight retention at 12 months (ß = -2.030, 95%CI: -3.486, -0.573) amongst all participants.
PFAS, in particular PFOA and PFHxS, in pregnancy are associated with altered patterns of GWG and postpartum adiposity with potential implications for fetal development and long-term maternal cardiometabolic health.
Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on ...reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children's health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.
Community gardens are credited for promoting health within neighborhoods, by increasing healthy food intake and exercise frequency. These benefits, however, are potentially undermined as urban soils ...are often contaminated from industrial legacies. The purpose of this study was to examine the perceived benefits of participation and risks of soil contamination within urban community gardens, and factors associated with soil contamination concerns. Ninety-three gardeners were interviewed across 20 community gardens in St. Louis, Missouri between June and August 2015. Surveys included questions on demographics, gardening practices, and perceptions of community gardening. Multilevel logistic models assessed how gardener demographics, gardening practices, and garden characteristics were associated with soil contamination concerns. Common perceived benefits of community gardening were community building (68.8%), healthy and fresh food (35.5%), and gardening education (18.3%). Most gardeners (62.4%) were not concerned about soil contamination, but nearly half (48.4%) stated concerns about heavy metals. Black race was significantly associated with soil contamination concerns (OR 5.47, 95% CI 1.00–30.15, p = .04). Community gardens offer numerous social and health benefits. Although most gardeners were not concerned about soil contamination, black gardeners were more likely to have concerns. Garden leaders should provide resources to gardeners to learn about soil contamination and methods to manage their risk, particularly in minority neighborhoods.
Purpose of Review
Pregnant women and their offspring are vulnerable to the adverse effects of environmental and psychosocial stressors, individually and in combination. Here, we review the literature ...on how air pollution and metal exposures may interact with structural and individual-level stressors (including poverty and stressful life events) to impact perinatal and child outcomes.
Recent Findings
The adverse associations between air pollution and metal exposures and adverse infant and child health outcomes are often exacerbated by co-exposure to psychosocial stressors. Although studies vary by geography, study population, pollutants, stressors, and outcomes considered, the effects of environmental exposures and psychosocial stressors on early health outcomes are sometimes stronger when considered in combination than individually.
Summary
Environmental and psychosocial stressors are often examined separately, even though their co-occurrence is widespread. The evidence that combined associations are often stronger raises critical issues around environmental justice and protection of vulnerable populations.
Some disinfection byproducts (DBPs) are teratogens based on toxicological evidence. Conventional use of predominant DBPs as proxies for complex mixtures may result in decreased ability to detect ...associations in epidemiological studies.
We assessed risks of obstructive genitourinary birth defects (OGDs) in relation to 12 DBP mixtures and 13 individual component DBPs.
We designed a nested registry-based case-control study (210 OGD cases; 2100 controls) in Massachusetts towns with complete quarterly 1999-2004 data on four trihalomethanes (THMs) and five haloacetic acids (HAAs). We estimated temporally-weighted average DBP exposures for the first trimester of pregnancy. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for OGD in relation to individual DBPs, unweighted mixtures, and weighted mixtures based on THM/HAA relative potency factors (RPF) from animal toxicology data for full-litter resorption, eye defects, and neural tube defects.
We detected elevated aORs for OGDs for the highest of bromodichloromethane (aOR = 1.75; 95% CI: 1.15-2.65), dibromochloromethane (aOR = 1.71; 95% CI: 1.15-2.54), bromodichloroacetic acid (aOR = 1.56; 95%CI: 0.97-2.51), chlorodibromoacetic acid (aOR = 1.97, 95% CI: 1.23-3.15), and tribromoacetic acid (aOR = 1.90; 95%CI: 1.20-3.03). Across unweighted mixture sums, the highest aORs were for the sum of three brominated THMs (aOR = 1.74; 95% CI: 1.15-2.64), the sum of six brominated HAAs (aOR = 1.43; 95% CI: 0.89-2.31), and the sum of nine brominated DBPs (aOR = 1.80; 95% CI: 1.05-3.10). Comparing eight RPF-weighted to unweighted mixtures, the largest aOR differences were for two HAA metrics, which both were higher with RPF weighting; other metrics had reduced or minimally changed ORs in RPF-weighted models.
PDF
