Exposure to Per- and Polyfluoroalkyl Substances and Breast Cancer Risk: A Systematic Review and Meta-analysis of Epidemiologic Studies.

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RR) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (e.g., a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR=0.95, 95% confidence interval [CI]:0.77-1.18; perfluorooctane sulfonate [PFOS] RR=0.98, 95%CI: 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR=1.16, 95%CI: 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk-of-bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association.

Residential proximity to toxic metal-emitting industrial sites and toenail metal concentrations in a United States-wide prospective cohort.

BACKGROUND: Industrial facilities across the United States (US) release millions of pounds of toxic chemicals, including metals. Exposure to toxic metals has been associated with adverse health outcomes, but there is limited evidence on the association between living near metal-releasing facilities and the body burden of emitted compounds. OBJECTIVE: To investigate the association between residential proximity to toxic metal-emitting industrial facilities and toenail metal concentrations and to evaluate whether associations differed by race. METHODS: In a sample of 1556 non-Hispanic Black (32.5%) and non-Hispanic White (67.5%) women from the Sister Study, we used the US Environmental Protection Agency Toxics Release Inventory to identify metal-emitting facilities within 3, 5, and 10 km of participants' baseline residences. We measured toenail concentrations (µg/g) of arsenic, cadmium, cobalt, chromium, and lead. Using multivariable linear regression, we examined associations between residential proximity to and emissions from metal-emitting facilities and toenail metal concentrations, stratifying by race. We explored modification of race-stratified associations by neighborhood deprivation, using the Area Deprivation Index (ADI). RESULTS: Black participants were more likely to reside within 3 km of chromium-releasing facilities and 5 and 10 km of all observed metal-emitting sites. Living near metal-releasing facilities was not associated with higher toenail metal concentrations overall. Among Black women, higher chromium emissions exposure was associated with higher toenail chromium levels (ßTertile3vs.non-exposed = 2.36 µg/g, 95% CI = 0.63, 4.10). An association with lead was observed among Black women residing in the most deprived areas (≥75th ADI percentile: ß = 3.08 µg/g, 95% CI = 1.46, 4.71). No associations were observed for White participants. CONCLUSIONS: Despite low exposure prevalence, our findings suggest that living near chromium- and lead-releasing facilities, especially at shorter distances, may be associated with higher corresponding toenail metal levels among Black women, particularly those residing in the most disadvantaged areas.

Evaluation of the Use of Saliva Metabolome as a Surrogate of Blood Metabolome in Assessing Internal Exposures to Traffic-Related Air Pollution.

In the omics era, saliva, a filtrate of blood, may serve as an alternative, noninvasive biospecimen to blood, although its use for specific metabolomic applications has not been fully evaluated. We demonstrated that the saliva metabolome may provide sensitive measures of traffic-related air pollution (TRAP) and associated biological responses via high-resolution, longitudinal metabolomics profiling. We collected 167 pairs of saliva and plasma samples from a cohort of 53 college student participants and measured corresponding indoor and outdoor concentrations of six air pollutants for the dormitories where the students lived. Grand correlation between common metabolic features in saliva and plasma was moderate to high, indicating a relatively consistent association between saliva and blood metabolites across subjects. Although saliva was less associated with TRAP compared to plasma, 25 biological pathways associated with TRAP were detected via saliva and accounted for 69% of those detected via plasma. Given the slightly higher feature reproducibility found in saliva, these findings provide some indication that the saliva metabolome offers a sensitive and practical alternative to blood for characterizing individual biological responses to environmental exposures.

Serum per- and polyfluoroalkyl substance (PFAS) concentrations and predictors of exposure among pregnant African American women in the Atlanta area, Georgia.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with adverse health outcomes, especially when exposure occurs within sensitive time windows such as the pre- and post-natal periods and early childhood. However, few studies have focused on PFAS exposure distribution and predictors in pregnant women, especially among African American women. We quantified serum concentrations of the four most common PFAS collected in all 453 participants and an additional 10 PFAS in 356 participants who were pregnant African American women enrolled from 2014 to 2018 in Atlanta, Georgia, and investigated the sociodemographic predictors of exposure. Additional home environment and behavior predictors were also examined in 130 participants. Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in >95% of the samples with PFOS having the highest concentrations (geometric mean (GM) 2.03 ng/mL). N-Methyl perfluorooctane sulfonamido acetic acid (NMeFOSAA), perfluoropentanoic acid (PFPeA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were found in 40-50% of the samples, whereas the detection frequencies for the other six PFAS were below 15%. When compared to National Health and Nutrition Examination Survey (NHANES) participants matching sex, race, and age with this study, our results showed similar concentrations of most PFAS, but higher concentrations of PFHxS (GM 0.99 ng/mL in this study; 0.63 and 0.4 ng/mL in NHANES, 2014-2015 and 2016-2017 cycles). A decline in concentrations over the study period was found for most PFAS but not PFPeA. In adjusted models, education, sampling year, parity, BMI, tobacco and marijuana use, age of house, drinking water source, and cosmetic use were significantly associated with serum PFAS concentrations. Our study reports the first PFAS exposure data among pregnant African American women in the Atlanta area, Georgia. The identified predictors will facilitate the setting of research priorities and enable development of exposure mitigation strategies.

Associations of single and multiple per- and polyfluoroalkyl substance (PFAS) exposure with vitamin D biomarkers in African American women during pregnancy.

Vitamin D has been linked to various physiological functions in pregnant women and their fetuses. Previous studies have suggested that some per- and polyfluoroalkyl substances (PFAS) may alter serum vitamin D concentrations. However, no study has investigated the relationship between PFAS and vitamin D in pregnant women. This study aims to evaluate the associations of serum PFAS with serum total and free 25-hydroxyvitamin D (25(OH)D) during pregnancy in a cohort of African American women in Atlanta, GA. Blood samples from 442 participants were collected in early pregnancy (8-14 weeks of gestation) for PFAS and 25(OH)D measurements, and additional samples were collected in late pregnancy (24-30 weeks) for the second 25(OH)D measurements. We fit multivariable linear regressions and weighted quantile sum (WQS) regressions to estimate the associations of individual PFAS and their mixtures with 25(OH)D concentrations. We found mostly positive associations of total 25(OH)D with PFHxS (perfluorohexane sulfonic acid), PFOS (perfluorooctane sulfonic acid), PFDA (perfluorodecanoic acid), and NMeFOSAA (N-methyl perfluorooctane sulfonamido acetic acid), and negative associations with PFPeA (perfluoropentanoic acid). For free 25(OH)D, positive associations were observed with PFHxS, PFOS, PFOA (perfluorooctanoic acid), and PFDA, and a negative association with PFPeA among the women with male fetuses in the models using 25(OH)D measured in late pregnancy. In mixture models, a quartile increase in WQS index was associated with 2.88 ng/mL (95%CI 1.14-4.59) and 5.68 ng/mL (95%CI 3.31-8.04) increases in total 25(OH)D measured in the early and late pregnancy, respectively. NMeFOSAA, PFDA, and PFOS contributed the most to the overall effects among the eight PFAS. No association was found between free 25(OH)D and the PFAS mixture. These results suggest that PFAS may affect vitamin D biomarker concentrations in pregnant African American women, and some of the associations were modified by fetal sex.

Inhibition of Epstein-Barr virus lytic cycle by an ethyl acetate subfraction separated from Polygonum cuspidatum root and its major component, emodin.

Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and its major component, emodin, for their capacity to inhibit the Epstein-Barr virus (EBV) lytic cycle. The cell viability was determined by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The expression of EBV lytic proteins was analyzed by immunoblot, indirect immunofluorescence and flow cytometric assays. Real-time quantitative PCR was used to assess the EBV DNA replication and the transcription of lytic genes, including BRLF1 and BZLF1. Results showed that the F3 and its major component emodin inhibit the transcription of EBV immediate early genes, the expression of EBV lytic proteins, including Rta, Zta, and EA-D and reduces EBV DNA replication, showing that F3 and emodin are potentially useful as an anti-EBV drug.

Use of personal care product mixtures and incident hormone-sensitive cancers in the Sister Study: A U.S.-wide prospective cohort.

BACKGROUND: Personal care products (PCPs), a source of endocrine-disrupting chemical exposure, may be associated with the risk of hormone-sensitive cancers. Few studies have investigated associations for PCP use with the incidence of hormone-sensitive cancers or considered the joint effect of multiple correlated PCPs. We examined associations between frequently used, or "everyday", PCPs and incident cancers of the breast, ovary, and uterus with a fucus on the joint effect of multiple product exposure. METHODS: Sister Study participants (n=49 899) self-reported frequency of use in the year before enrollment (2003-2009) for 41 PCPs. Using five-level frequency categories based on questionnaire options, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the associations between multiple PCP use and incident breast, ovarian, and uterine cancer using quantile-based g-computation with Cox proportional hazards regression as the underlying model. Multiple PCP use was examined using groupings (beauty, hygiene, and skincare products) determined by both a priori knowledge and Spearman correlation coefficients for co-occurring product use. Associations between individual PCPs and the three cancers were also examined using Cox proportional hazards models coupling with Benjamini-Hochberg procedure for multiple comparisons. RESULTS: Over an average of 11.6 years, 4 226 breast, 277 ovarian, and 403 uterine cancer cases were identified. Positive associations were observed between the hygiene mixture and ovarian cancer (HR=1.35, 95%CI=1.00, 1.83) and the beauty mixture with postmenopausal breast cancer (HR=1.08, 95%CI=1.01, 1.16). Additionally, we observed an inverse association between the skincare mixture and breast cancer (HR=0.91, 95%CI=0.83, 0.99). No significant associations were observed for individual products after corrected for multiple comparison. CONCLUSIONS: Findings from this multi-product, joint-effect approach contribute to the growing body of evidence for associations between PCPs and breast cancer and provides novel information on ovarian and uterine cancer.

Personal Care Product Use during Puberty and Incident Breast Cancer among Black, Hispanic/Latina, and White Women in a Prospective US-Wide Cohort.

BACKGROUND: Some personal care products (PCPs) contain endocrine-disrupting chemicals that may affect breast cancer (BC) risk. Patterns of use vary by race and ethnicity. Use often starts in adolescence, when rapidly developing breast tissue may be more susceptible to environmental carcinogens. Few studies have examined associations of BC with PCP use during this susceptible window. OBJECTIVES: We characterized race and ethnicity-specific patterns of PCP use at 10-13 years of age and estimated associations of use with incident BC. METHODS: At enrollment (2003-2009), Sister Study participants (n=4,049 Black, 2,104 Latina, and 39,312 White women) 35-74 years of age reported use of 37 "everyday" PCPs during the ages of 10-13 y (did not use, sometimes, or frequently used). We conducted race and ethnicity-specific latent class analyses to separately identify groups of women with similar patterns of beauty, hair, and skincare/hygiene product use. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of identified PCP classes and single products with incident BC using Cox proportional hazards regression. RESULTS: During a mean follow-up time of 10.8 y, 280 Black, 128 Latina, and 3,137 White women were diagnosed with BC. Classes of adolescent PCP use were not clearly associated with BC diagnosis among Black, Latina, or White women. HRs were elevated but imprecise for frequent nail product and perfume use in Black women (HR=1.34; 95% CI: 0.85, 2.12) and greater hair product use in Black (HR=1.28; 95% CI: 0.91, 1.80) and Latina (HR=1.42; 95% CI: 0.81, 2.48) women compared with lighter use. In single-product models, we observed higher BC incidence associated with frequent use of lipstick, nail products, pomade, perfume, makeup remover, and acne/blemish products in at least one group. DISCUSSION: This work provides some support for the hypothesis that PCP use during puberty is associated with BC risk. More research is needed to confirm these novel findings. https://doi.org/10.1289/EHP13882.

Outdoor air pollution exposure and uterine cancer incidence in the Sister Study.

BACKGROUND: Outdoor air pollution is a ubiquitous exposure that includes endocrine-disrupting and carcinogenic compounds that may contribute to the risk of hormone-sensitive outcomes such as uterine cancer. However, there is limited evidence about the relationship between outdoor air pollution and uterine cancer incidence. METHODS: We investigated the associations of residential exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2) with uterine cancer among 33 417 Sister Study participants with an intact uterus at baseline (2003-2009). Annual average air pollutant concentrations were estimated at participants' geocoded primary residential addresses using validated spatiotemporal models. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between time-varying 12-month PM2.5 (µg/m3) and NO2 (parts per billion; ppb) averages and uterine cancer incidence. RESULTS: Over a median follow-up period of 9.8 years, 319 incident uterine cancer cases were identified. A 5-ppb increase in NO2 was associated with a 23% higher incidence of uterine cancer (hazard ratio = 1.23, 95% confidence interval = 1.04 to 1.46), especially among participants living in urban areas (hazard ratio = 1.53, 95% confidence interval = 1.13 to 2.07), but  PM2.5 was not associated with increased uterine cancer incidence. CONCLUSION: In this large US cohort, NO2, a marker of vehicular traffic exposure, was associated with a higher incidence of uterine cancer. These findings expand the scope of health effects associated with air pollution, supporting the need for policy and other interventions designed to reduce air pollutant exposure.

Associations between use of chemical hair products and epigenetic age: Findings from the Sister Study.

Background: Hair products may be a source of harmful chemicals and have been linked to age-related health outcomes. We investigated whether the use of hair products is related to epigenetic age in a sample of Black (both Hispanic and non-Hispanic) and non-Hispanic White women. Methods: In a subset of 4358 participants aged 35-74 years from the Sister Study, we estimated cross-sectional associations between self-reported use of four chemical hair products (permanent dye, semipermanent dye, straighteners/relaxers, and hair permanents/body waves) in the year before enrollment (2003-2009) and three DNA methylation-based measures of epigenetic age (DunedinPACE, GrimAge age acceleration [GrimAgeAccel], and PhenoAge age acceleration [PhenoAgeAccel]) using survey-weighted multivariable linear regressions. Associations were estimated both overall and by self-identified race and ethnicity, adjusting for chronological age, socioeconomic and lifestyle factors, body mass index, menopausal status, and DNA methylation platform. Results: Associations between the use of hair products and the three epigenetic age measures were largely null. Use of hair permanents/body waves was modestly associated with higher DunedinPACE among all participants (ßever-never = 0.010; 95% confidence interval [CI] = 0.001, 0.019) and with lower PhenoAgeAccel among Black women (ßever-never = -1.53; 95% CI = -2.84, -0.21). Conclusion: In this US-based study, we found little evidence of associations between chemical hair product use and epigenetic age in Black and non-Hispanic White women. Observed associations were modest and largely not supported by dose-response relationships or were inconsistent across epigenetic age measures. Previously observed associations between chemical hair product use and aging-related health outcomes may not be explained by the biological aging pathways captured by DunedinPACE, GrimAgeAccel, or PhenoAgeAccel. Alternative biological pathways are worth investigating in racially diverse samples.

Air pollution and epigenetic aging among Black and White women in the US.

BACKGROUND: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women. OBJECTIVE: We examined associations of ambient particulate matter <2.5 µm and <10 µm in diameter (PM2.5 and PM10) and nitrogen dioxide (NO2) with DNA methylation, including epigenetic aging and individual CpG sites, and evaluated whether associations differ between Black and non-Hispanic White (NHW) women. METHODS: Validated models were used to estimate annual average outdoor residential exposure to PM2.5, PM10, and NO2 in a sample of self-identified Black (n=633) and NHW (n=3493) women residing in the contiguous US. We used sampling-weighted generalized linear regression to examine the effects of pollutants on six epigenetic aging measures (primary: DunedinPACE, GrimAgeAccel, and PhenoAgeAccel; secondary: Horvath intrinsic epigenetic age acceleration [EAA], Hannum extrinsic EAA, and skin & blood EAA) and epigenome-wide associations for individual CpG sites. Wald tests of nested models with and without interaction terms were used to examine effect measure modification by race/ethnicity. RESULTS: Black participants had higher median air pollution exposure than NHW participants. GrimAgeAccel was associated with both PM10 and NO2 among Black participants, (Q4 versus Q1, PM10: ß=1.09, 95% CI: 0.16-2.03; NO2: ß=1.01, 95% CI 0.08-1.94) but not NHW participants (p-for-heterogeneity: PM10=0.10, NO2=0.20). In Black participants, we also observed a monotonic exposure-response relationship between NO2 and DunedinPACE (Q4 versus Q1, NO2: ß=0.029, 95% CI: 0.004-0.055; p-for-trend=0.03), which was not observed in NHW participants (p-for-heterogeneity=0.09). In the EWAS, pollutants were significantly associated with differential methylation at 19 CpG sites in Black women and one in NHW women. CONCLUSIONS: In a US-wide cohort study, our findings suggest that air pollution is associated with DNA methylation alterations consistent with higher epigenetic aging among Black, but not NHW, women.

Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation.

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.

Use of Straighteners and Other Hair Products and Incident Uterine Cancer.

BACKGROUND: Hair products may contain hazardous chemicals with endocrine-disrupting and carcinogenic properties. Previous studies have found hair product use to be associated with a higher risk of hormone-sensitive cancers including breast and ovarian cancer; however, to our knowledge, no previous study has investigated the relationship with uterine cancer. METHODS: We examined associations between hair product use and incident uterine cancer among 33 947 Sister Study participants aged 35-74 years who had a uterus at enrollment (2003-2009). In baseline questionnaires, participants in this large, racially and ethnically diverse prospective cohort self-reported their use of hair products in the prior 12 months, including hair dyes; straighteners, relaxers, or pressing products; and permanents or body waves. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations between hair product use and uterine cancer using Cox proportional hazard models. All statistical tests were 2-sided. RESULTS: Over an average of 10.9 years of follow-up, 378 uterine cancer cases were identified. Ever vs never use of straightening products in the previous 12 months was associated with higher incident uterine cancer rates (HR = 1.80, 95% CI = 1.12 to 2.88). The association was stronger when comparing frequent use (>4 times in the past 12 months) vs never use (HR = 2.55, 95% CI = 1.46 to 4.45; Ptrend = .002). Use of other hair products, including dyes and permanents or body waves, was not associated with incident uterine cancer. CONCLUSION: These findings are the first epidemiologic evidence of association between use of straightening products and uterine cancer. More research is warranted to replicate our findings in other settings and to identify specific chemicals driving this observed association.

High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort.

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014-2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 µg/g creatinine and 3.69 µg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

Per- and polyfluoroalkyl substance (PFAS) exposure, maternal metabolomic perturbation, and fetal growth in African American women: A meet-in-the-middle approach.

BACKGROUND: Prenatal exposures to per- and polyfluoroalkyl substances (PFAS) have been linked to reduced fetal growth. However, the detailed molecular mechanisms remain largely unknown. This study aims to investigate biological pathways and intermediate biomarkers underlying the association between serum PFAS and fetal growth using high-resolution metabolomics in a cohort of pregnant African American women in the Atlanta area, Georgia. METHODS: Serum perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) measurements and untargeted serum metabolomics profiling were conducted in 313 pregnant African American women at 8-14 weeks gestation. Multiple linear regression models were applied to assess the associations of PFAS with birth weight and small-for-gestational age (SGA) birth. A high-resolution metabolomics workflow including metabolome-wide association study, pathway enrichment analysis, and chemical annotation and confirmation with a meet-in-the-middle approach was performed to characterize the biological pathways and intermediate biomarkers of the PFAS-fetal growth relationship. RESULTS: Each log2-unit increase in serum PFNA concentration was significantly associated with higher odds of SGA birth (OR = 1.32, 95% CI 1.07, 1.63); similar but borderline significant associations were found in PFOA (OR = 1.20, 95% CI 0.94, 1.49) with SGA. Among 25,516 metabolic features extracted from the serum samples, we successfully annotated and confirmed 10 overlapping metabolites associated with both PFAS and fetal growth endpoints, including glycine, taurine, uric acid, ferulic acid, 2-hexyl-3-phenyl-2-propenal, unsaturated fatty acid C18:1, androgenic hormone conjugate, parent bile acid, and bile acid-glycine conjugate. Also, we identified 21 overlapping metabolic pathways from pathway enrichment analyses. These overlapping metabolites and pathways were closely related to amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism perturbations. CONCLUSION: In this cohort of pregnant African American women, higher serum concentrations of PFOA and PFNA were associated with reduced fetal growth. Perturbations of biological pathways involved in amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism were associated with PFAS exposures and reduced fetal growth, and uric acid was shown to be a potential intermediate biomarker. Our results provide opportunities for future studies to develop early detection and intervention for PFAS-induced fetal growth restriction.

High-Flow Nasal Cannula versus Noninvasive Positive Pressure Ventilation in Patients with Heart Failure after Extubation: An Observational Cohort Study.

Noninvasive positive pressure ventilation (NPPV) has been widely applied in patients with high-risk extubation failure, including heart failure. High-flow nasal cannula (HFNC) has been demonstrated to benefit patients with heart failure by reducing cardiac preload. This study aimed to compare the effectiveness of HFNC to NPPV for preventing extubation failure in patients with heart failure. This 3-year retrospective and single-center cohort study included patients with heart failure with left ventricular ejection fraction <50% who received prophylactic HFNC or NPPV after scheduled extubation from January 2015 to January 2018 from a medical center with four adult intensive care units. Demographics, comorbidities, diagnosis, and weaning status were collected. The primary outcome was treatment failure within 72 hours after extubation, which was defined as escalation to NPPV or reintubation in the HFNC group and was defined as requiring reintubation in the NPPV group. Secondary outcomes were reintubation within 72 hours, reintubation, duration of stay, and mortality during the intensive care unit and hospital stay. Of the 104 patients analyzed, characteristics of 58 patients in the HFNC group and 46 patients in the NPPV group were compared. The treatment failure within 72 hours in the two groups was not significantly different (25.9% vs 13%, p=0.106). Hypoxemic respiratory failure related treatment failure was significantly higher in the HFNC group. Prophylactic HFNC as first-line therapy had a comparable rate of reintubation within 72 hours to the prophylactic NPPV alone (17.2% vs 13%, p=0.556). Other secondary outcomes were similar between the two groups. Among patients with heart failure, HFNC was not inferior to NPPV for preventing extubation failure and reintubation. However, in case of an impending respiratory failure, selective patients may benefit from rescue NPPV.

Serum concentrations of polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the Michigan PBB Registry 40 years after the PBB contamination incident.

Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in livestock feed. People who lived in the state were exposed to PBBs via several routes including ingestion, inhalation and skin absorption. PBBs sequestered in lipid-rich matrices such as adipose tissue, are slowly eliminated after entering the human body, and can also be transferred from a mother to her offspring through the placenta and breastfeeding. Due to the long biological half-lives of PBBs, as well as concerns from the exposed community, biomonitoring measurements were conducted from 2012 to 2015. Because of their similar structures, serum PBBs, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were all measured 40 years after the PBB contamination incident (N = 862). The serum PBB-153 levels among the original highly-exposed groups (i.e., chemical workers, the family of chemical workers, and individuals who lived on or received food from the contaminated farms) remains significantly higher than other Michigan residents. Several predictors such as sampling age, sex, and smoking status were significantly associated with the serum levels of some persistent organic pollutants (POPs). Higher average values and also wider ranges of serum POP levels were found in this study compared to the National Health and Nutrition Examination Survey (NHANES), with the most substantial difference in serum PBB-153. This was true for all groups of Michigan residents including those who were not part of the above-described highly-exposed groups. Moreover, the people born after the contamination incident began also have higher serum PBB-153 levels when compared with more recent NHANES data (2010-2014), which suggests potential intergenerational exposure and/or continued environmental exposure following the contamination period.

Employing a Fuzzy-Based Grey Modeling Procedure to Forecast China's Sulfur Dioxide Emissions.

Effective determination of trends in sulfur dioxide emissions facilitates national efforts to draft an appropriate policy that aims to lower sulfur dioxide emissions, which is essential for reducing atmospheric pollution. However, to reflect the current situation, a favorable emission reduction policy should be based on updated information. Various forecasting methods have been developed, but their applications are often limited by insufficient data. Grey system theory is one potential approach for analyzing small data sets. In this study, an improved modeling procedure based on the grey system theory and the mega-trend-diffusion technique is proposed to forecast sulfur dioxide emissions in China. Compared with the results obtained by the support vector regression and the radial basis function network, the experimental results indicate that the proposed procedure can effectively handle forecasting problems involving small data sets. In addition, the forecast predicts a steady decline in China's sulfur dioxide emissions. These findings can be used by the Chinese government to determine whether its current policy to reduce sulfur dioxide emissions is appropriate.