Breastfeeding as a Predictor of Serum Concentrations of Per- and Polyfluorinated Alkyl Substances in Reproductive-aged Women and Children: A Rapid Systematic Review

Purpose of Review: Per- and polyfluorinated alkyl substances (PFASs) are synthetic chemicals widely detected in human serum, and at low levels in breast milk. We conducted a rapid systematic review on breastfeeding practices and serum concentrations of PFASs – specifically PFOS and PFOA - among reproductive-aged women and young children using the Navigation Guide systematic review methodology. Recent Findings: We included 14 studies examining associations between breastfeeding and PFASs in infants/toddlers or pregnant/postnatal women. Breastfeeding was significantly associated with lower PFASs exposure among women and higher PFASs exposure among children. Summary: We concluded there was “sufficient” evidence supporting an association between breastfeeding and serum PFASs concentrations among women, and “limited” evidence of an association among children due to issues with sample size, confounding, and exposure assessment. These findings reinforce that lactation is an important excretion route of PFASs for women, and that breast milk may be an important exposure pathway for young children

Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia

Purpose: Neurodevelopmental disorders (NDDs) encompass a spectrum of genetically heterogeneous disorders with features that commonly include developmental delay, intellectual disability, and autism spectrum disorders. We sought to delineate the molecular and phenotypic spectrum of a novel neurodevelopmental disorder caused by variants in the GNAI1 gene. Methods: Through large cohort trio-based exome sequencing and international data-sharing, we identified 24 unrelated individuals with NDD phenotypes and a variant in GNAI1, which encodes the inhibitory Gαi1 subunit of heterotrimeric G-proteins. We collected detailed genotype and phenotype information for each affected individual. Results: We identified 16 unique variants in GNAI1 in 24 affected individuals; 23 occurred de novo and 1 was inherited from a mosaic parent. Most affected individuals have a severe neurodevelopmental disorder. Core features include global developmental delay, intellectual disability, hypotonia, and epilepsy. Conclusion: This collaboration establishes GNAI1 variants as a cause of NDDs. GNAI1-related NDD is most often characterized by severe to profound delays, hypotonia, epilepsy that ranges from self-limiting to intractable, behavior problems, and variable mild dysmorphic features

Black Women\u27s Psychosocial Experiences with Seeking Surgical Treatment for Uterine Fibroids: Implications for Clinical Practice

© 2021 Jacobs Institute of Women\u27s Health Introduction: Black women are more likely to undergo surgery for uterine fibroids compared with non-Black women. However, few studies have characterized the psychosocial experiences of Black women seeking fibroid treatment. We aimed to identify factors that shape Black women\u27s fibroid management decisions; explore how discrimination based on race, class, and gender feature in treatment-seeking experiences, and compare experiences across age and socioeconomic status. Methods: We conducted semistructured interviews with 37 Black women undergoing surgery for fibroid management. We used a thematic analysis to code transcripts and identify themes. Results: Participants were predominately single, college educated, and insured. Respondents reported that patient–doctor interactions, support from social networks, fertility consequences, and fear of fibroid malignancy influenced their fibroid management decisions. Knowledge and perceptions of fibroids were also influenced by community norms and differed by socioeconomic status; women of higher socioeconomic status had greater fibroid awareness than women of lower socioeconomic status. Discrimination was discussed in the context of historical inequity against Black women, with one participant questioning whether Black women were valued less in clinical settings compared with non-Black women. Although several women discussed positive experiences seeking fibroids care, others expressed medical mistrust or said that alternative management options were not offered by clinicians. Conclusions: Fibroid management decisions were influenced not only by interactions with clinicians and social networks, and concerns about fertility and fibroid malignancy, but also by broader social and historical conditions. These findings suggest that clinicians should deliver intersectional gynecologic care that centers the voices of Black women seeking fibroid treatment

Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis

BACKGROUND: Fast food consumption is associated with biomarkers of ortho-phthalates exposures. However, the chemical content of fast food is unknown; certain ortho-phthalates (i.e., di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP)) have been phased out and replaced with other plasticizers (e.g., dioctyl terephthalate (DEHT)). OBJECTIVE: We conducted a preliminary study to examine ortho-phthalate and replacement plasticizer concentrations in foods and food handling gloves from U.S. fast food restaurants. METHODS: We obtained hamburgers, fries, chicken nuggets, chicken burritos, cheese pizza (n = 64 food samples) and gloves (n = 3) from restaurants and analyzed them for 11 chemicals using gas chromatography mass spectrometry. RESULTS: We found DEHT at the highest concentrations in both foods (n = 19; median = 2510 µg/kg; max = 12,400 µg/kg) and gloves (n = 3; range: 28-37% by weight). We detected DnBP and DEHP in 81% and 70% of food samples, respectively. Median DEHT concentrations were significantly higher in burritos than hamburgers (6000 µg/kg vs. 2200 µg/kg; p \u3c 0.0001); DEHT was not detected in fries. Cheese pizza had the lowest levels of most chemicals. SIGNIFICANCE: To our knowledge, these are the first measurements of DEHT in food. Our preliminary findings suggest that ortho-phthalates remain ubiquitous and replacement plasticizers may be abundant in fast food meals. IMPACT STATEMENT: A selection of popular fast food items sampled in this study contain detectable levels of replacement plasticizers and concerning ortho-phthalates. In addition, food handling gloves contain replacement plasticizers, which may be a source of food contamination. These results, if confirmed, may inform individual and regulatory exposure reduction strategies

Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study.

© The Author(s) 2020. Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction \u3c 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids

Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study

© The Author(s) 2020. Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction \u3c 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids

Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.

PURPOSE: Neurodevelopmental disorders (NDDs) encompass a spectrum of genetically heterogeneous disorders with features that commonly include developmental delay, intellectual disability, and autism spectrum disorders. We sought to delineate the molecular and phenotypic spectrum of a novel neurodevelopmental disorder caused by variants in the GNAI1 gene. METHODS: Through large cohort trio-based exome sequencing and international data-sharing, we identified 24 unrelated individuals with NDD phenotypes and a variant in GNAI1, which encodes the inhibitory G?i1 subunit of heterotrimeric G-proteins. We collected detailed genotype and phenotype information for each affected individual. RESULTS: We identified 16 unique variants in GNAI1 in 24 affected individuals; 23 occurred de novo and 1 was inherited from a mosaic parent. Most affected individuals have a severe neurodevelopmental disorder. Core features include global developmental delay, intellectual disability, hypotonia, and epilepsy. CONCLUSION: This collaboration establishes GNAI1 variants as a cause of NDDs. GNAI1-related NDD is most often characterized by severe to profound delays, hypotonia, epilepsy that ranges from self-limiting to intractable, behavior problems, and variable mild dysmorphic features.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (6 month embargo), submitted versio