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This study explores a Capstone course’s pedagogical process and considers both the challenges and triumphs that emerge from experiential learning within a news desert region. The research employs micro-ethnographic methods to analyze the learning outcomes gleaned by both students and instructors of one magazine publishing Capstone course over the timespan of 9 years, 2014 to 2023. The research acknowledges the pedagogical evolution of the Capstone course as both a means of assessment and workforce preparation and seeks to add the concept of the Capstone as a venue for service and community journalism.

Human exposure to phthalates is widespread, but assessment of variability across pregnancy has been hampered by short half-lives of phthalate biomarkers and a few repeated measures in prior studies. We aimed to characterize the variability and longitudinal profiles of phthalate and replacement biomarkers across pregnancy. Within the Human Placenta and Phthalates Study, 303 pregnant women provided urine samples at up to 8 visits across gestation. Concentrations of 14 metabolites of phthalates and 4 metabolites of replacements were quantified in each sample, and subject-specific averages within each trimester were calculated. We examined variability in individual biomarker concentrations across the 8 visits, within trimesters, and across trimester-specific averages using intraclass correlation coefficients (ICCs). To explore longitudinal exposure biomarker profiles, we applied group-based trajectory modeling to trimester-specific averages over pregnancy. Pooling multiple visits into trimester-specific averages improved the ICCs for all biomarkers. Most biomarkers generally showed stable concentrations across gestation, i.e., high-, medium-, and low-concentration profiles, with small proportions of participants falling into the “high”-exposure groups. Variability over pregnancy is likely attributable to random fluctuations around a baseline exposure rather than true changes in concentrations over time.

IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Preterm birth is a leading cause of neonatal mortality. Preterm birth is a public health burden, particularly in the United States, where approximately 10% of deliveries are preterm. Although the underlying cause of most preterm births is unknown, environmental chemical exposures (such as phthalates) possibly contribute. Phthalates are common in consumer products, and exposure can occur through diet, personal care products, and even household dust. Consequently, exposure is ubiquitous for pregnant individuals. Prenatal phthalate exposure has been associated with adverse neurodevelopment in children and disordered development of the male reproductive tract. This study reviewed 16 prospective studies conducted within the United States to pool individual-level data to examine prenatal urinary biomarkers of phthalate exposure and preterm birth. In addition, potential influence of exposure to overall phthalate mixture was assessed to determine the potential impact of reduced exposure on preterm birth.Results of the study indicated that of 6045 pregnant women, 539 (9%) delivered preterm. Overall, of the entire included cohort, 802 individuals were Black (13.3%), 2576 were White (42.6%), 2323 were Latina (38.4%), and 328 had other race identity (including Native Hawaiian, Alaskan Native, or American Indian). Characteristics of participants were similar between those who delivered preterm versus term. Some 96% of urine samples displayed detectable concentrations of urinary phthalate metabolites. As demonstrated by regression analyses, higher concentrations of most phthalate metabolites bore an association of slightly higher odds (12%–16% higher) for preterm birth. In addition, the study estimated that reducing the mixture of phthalate metabolite concentrations by 10%, 30%, or 50%, respectively, could prevent 1.8, 5.9, and 11.1 preterm births per 1000 live births.The study found a relationship between higher maternal pregnancy concentrations of urinary phthalate metabolites and preterm birth. The findings of this study identify a potential benefit of phthalate exposure reduction among pregnant individuals via either regulations or behavioral interventions. Because phthalate exposure can occur through many environments and sources, the US Consumer Product Safety Commission has attempted to pinpoint major sources of phthalate exposure and has determined that the predominate exposures appear to occur through food and medications, although uncertainty in the primary source of exposure remains. Phthalate exposure also widely varies in the United States based on several factors such as whether a person is at a disadvantaged socioeconomic status, is pregnant, or is of a marginalized race or ethnicity. Targeted interventions, such as altering personal care products, is made challenging as consumers are not readily able to access accurate ingredients lists. In the United States, for example, fragrance ingredient lists are not required to list phthalates when they are included in the product.Diet interventions intending to reduce phthalate exposure have had mixed results. Although federally mandated restrictions have limited the use of phthalates in products for children, few such restrictions exist for products intended for pregnant individuals. As 28 phthalates are currently allowed as food additives or in food contact materials, they are difficult to avoid. Mitigation of population-level health effects from phthalates through regulatory means would be most effective when considering phthalates not as individual chemicals, but rather as a class.This study found that higher concentrations of several urinary phthalate metabolites in pregnancy were associated with preterm birth, a consistent finding across 16 prospective US studies. Such findings emphasize the importance of the development of policy measures and public health around phthalate exposure reduction, especially among pregnant individuals.

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Supplemental Digital Content is available in the text.Limit of detection (LOD) issues are ubiquitous in exposure assessment. Although there is an extensive literature on modeling exposure data under such imperfect measurement processes, including likelihood-based methods and multiple imputation, the standard practice continues to be naïve single imputation by a constant (e.g., ). In this article, we consider the situation where, due to the practical logistics of data accrual, sampling, and resource constraints, exposure data are analyzed in multiple batches where the LOD and the proportion of censored observations differ across batches. Compounding this problem is the potential for nonrandom assignment of samples to each batch, often driven by enrollment patterns and biosample storage. This issue is particularly important for binary outcome data where batches may have different levels of outcome enrichment. We first consider variants of existing methods to address varying LODs across multiple batches. We then propose a likelihood-based multiple imputation strategy to impute observations that are below the LOD while simultaneously accounting for differential batch assignment. Our simulation study shows that our proposed method has superior estimation properties (i.e., bias, coverage, statistical efficiency) compared to standard alternatives, provided that distributional assumptions are satisfied. Additionally, in most batch assignment configurations, complete-case analysis can be made unbiased by including batch indicator terms in the analysis model, although this strategy is less efficient relative to the proposed method. We illustrate our method by analyzing data from a cohort study in Puerto Rico that is investigating the relation between endocrine disruptor exposures and preterm birth.

Exposure to environmental chemicals such as phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined urinary 8-iso-prostaglandin F2α(8-iso-PGF2α) as the oxidative stress biomarker. However, 8-iso-PGF2αalso originates from enzymatic sources linked to inflammation. Therefore, associations between phthalates and 8-iso-PGF2αcould have been misinterpreted. To clarify this, the 8-iso-PGF2α/prostaglandin F2αratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF2αand estimate their associations with phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary phthalate metabolites were associated with a significant increase in 8-iso-PGF2α. For example, a 22.4% higher 8-iso-PGF2αconcentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono-n-butyl phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF2α. In contrast, monocarboxy-isononyl phthalate and monoisononyl phthalate (MNP) were associated with both sources of 8-iso-PGF2α. Metabolites of the phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2α, which is interesting because DINCH metabolites and MNP have structural similarities.In conclusion, phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF2α. Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of phthalates.

Overt thyroid disease in pregnancy is a known risk factor for abnormal fetal growth and development. Data on the effects of milder forms of variation in maternal thyroid function on intrauterine growth are less well examined.

Personal care product use is a well-established pathway of exposure for notable endocrine disrupting compounds (EDCs), including phthalates, parabens, triclosan, benzophenone-3 (BP3), and bisphenol-A. We utilized questionnaire data from the National Health and Nutrition Examination Survey 2009–2012 cycles to examine the associations between use of sunscreen and mouthwash and urinary concentrations of phthalate metabolites and phenols in a nationally representative population of US adults (n=3529). Compared with individuals who reported “Never” using mouthwash, individuals who reported daily use had significantly elevated urinary concentrations of mono-ethyl phthalate, methyl and propyl parabens, and BP3 (28%, 30%, 39%, and 42% higher, respectively). Individuals who reported “Always” using sunscreen had significantly higher urinary concentrations of triclosan, methyl, ethyl, and propyl parabens, and BP3 (59%, 92%, 102%, 151%, and 510% higher, respectively) compared with “Never” users of sunscreen. Associations between exposure biomarkers and sunscreen use were stronger in women compared with men, and associations with mouthwash use were generally stronger in men compared with women. These results suggest that sunscreen and mouthwash may be important exposure sources for EDCs.

Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes.

Context:Recent research suggests that environmental exposure to endocrine-disrupting chemicals may alter circulating 25-hydroxyvitamin D [25(OH)D] levels in humans. To date, no studies have assessed the associations between phthalates and bisphenol A (BPA) and total 25(OH)D in the U.S. general population.Objective:To explore relationships between urinary concentrations of 11 phthalate metabolites and BPA and serum total 25(OH)D in a representative sample of U.S. adults.Design:A cross-sectional study.Setting:U.S. National Health and Nutrition Examination Survey, 2005–2010.Patients or Other Participants:U.S. general adult population (aged ≥20 years).Interventions:NoneMain Outcome Measures:Serum total 25(OH)D measured by liquid chromatography-tandem mass spectrometry.Results:Metabolites of di(2-ethylhexyl) phthalate (DEHP) were consistently inversely associated with total 25(OH)D in the overall study population and in gender-stratified models. In the overall population, we detected a significant inverse relationship for the molar sum of DEHP metabolites (ΣDEHP), where an interquartile range increase in ΣDEHP was associated with a 1.90% decrease (95% confidence interval [CI], −3.64, −0.17) in total 25(OH)D. A positive association was detected for monoethyl phthalate. For BPA, we found a statistically significant inverse relationship in women, but not in men. In women, an interquartile range increase in urinary BPA was associated with a 3.71% decrease (95% CI, −6.41, −1.02) in total 25(OH)D.Conclusions:Overall, our results provide suggestive evidence that environmental exposure to phthalates and BPA may alter circulating levels of total 25(OH)D in adults. Future human and animal studies are required to resolve the direction, temporality, and impact of these relationships.

Context:Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis.Objective:To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis.Design:Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring.Setting:Public maternity hospitals in Mexico City.Patients or Other Participants:Women recruited during pregnancy; offspring recruited for follow-up at age 8–14 years (n = 250).Interventions:None.Main Outcome Measures:Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance.Results:Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8–14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P= .02) and higher leptin among girls (P= .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P= .01).Conclusions:Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.

IMPORTANCE: Preterm birth is a leading cause of neonatal mortality, with a variety of contributing causes and risk factors. Environmental exposures represent a group of understudied, but potentially important, factors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. OBJECTIVE: To assess the relationship between phthalate exposure during pregnancy and preterm birth. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study was conducted at Brigham and Women’s Hospital, Boston, Massachusetts. Women were recruited for a prospective observational cohort study from 2006-2008. Each provided demographic data, biological samples, and information about birth outcomes. From within this group, we selected 130 cases of preterm birth and 352 randomly assigned control participants, and we analyzed urine samples from up to 3 time points during pregnancy for levels of phthalate metabolites. EXPOSURE: Phthalate exposure during pregnancy. MAIN OUTCOMES AND MEASURES: We examined associations between average levels of phthalate exposure during pregnancy and preterm birth, defined as fewer than 37 weeks of completed gestation, as well as spontaneous preterm birth, defined as preterm preceded by spontaneous preterm labor or preterm premature rupture of the membranes (n = 57). RESULTS: Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-n-butyl phthalate (MBP), were significantly higher in cases compared with control participants. In adjusted models, MEHP, MECPP, and Σ DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate, MECPP, Σ DEHP, MBP, and mono-(3-carboxypropyl) phthalate metabolite levels were all associated with significantly elevated odds of prematurity. CONCLUSIONS AND RELEVANCE: Women exposed to phthalates during pregnancy have significantly increased odds of delivering preterm. Steps should be taken to decrease maternal exposure to phthalates during pregnancy.

Cellular treatments for repairing diseased tissues represent a promising clinical strategy. Umbilical cord tissue-derived cells (UTC) are a unique source of cells with a low immunogenic profile and potential for tissue repair. By using UTC from miniature swine, we previously demonstrated that despite their low immunogenic phenotype, UTC could induce an immune response under certain inflammatory conditions and after multiple subcutaneous (SC) injections. Given that repeat dosing of cells may be necessary to achieve a lasting therapeutic benefit, in this study, we examined approaches to avoid an immune response to multiple SC injections of UTC.

In the event of a composite allograft failure, damage to the recipient tissues may make retransplantation impossible. This study aimed to quantify the damage after composite allograft failure to assess whether retransplantation is feasible.

Prenatal exposure to nonpersistent chemicals such as phthalates, bisphenols, and organophosphate (OP) pesticides is ubiquitous and occurs in mixtures. So far, epidemiological studies investigating neurodevelopmental consequences of these exposures have mainly been restricted to single-pollutant models. Thus, we studied the association between prenatal exposure to nonpersistent chemical mixtures and child IQ and emotional and behavioral problems. Data came from 782 mother–child pairs. Eleven phthalate, one bisphenol, and five OP pesticide urinary exposure biomarkers were measured three times during pregnancy and averaged. Nonverbal IQ, internalizing and attention problems, aggressive behavior, and autistic traits were assessed at child age 6 years. We used quantile g-computation to estimate the change in each outcome per quartile increase in all chemicals within the mixture. Higher exposure to the mixture was associated with lower nonverbal IQ (−4.0 points (95%CI = −7.0, −1.0), −5.5 points (95%CI = −10.2, −0.9), and −4.6 points (95%CI = −10.8, 1.5) for the second, third, and fourth quartile, respectively, compared to the first quartile). These results were mainly driven by the phthalate mixture. No association was observed with emotional and behavioral problems. Prenatal exposure to nonpersistent chemical mixtures was associated with lower nonverbal IQ in children. Exposure to chemical mixtures during gestation is universal and may impact neurodevelopment.

Non-myeloablative hematopoietic cell transplantation (HCT) followed by delayed donor leukocyte infusion (DLI) is a promising immunotherapeutic approach to the treatment of hematologic malignancies. Major limitations of this approach, however, include the risks of graft failure, graft-versus-host disease (GVHD), and infection. MHC-defined, MGH miniature swine provide a pre-clinical model for studies of HCT. Similar to humans, pigs that receive haploidentical HCT following standard myeloablative conditioning develop severe GVHD or hematopoietic failure. We previously developed a successful haploidentical HCT protocol in miniature swine using a minimally myelosuppressive regimen consisting of a very low-dose of total body irradiation (100cGy TBI) in combination with transient recipient T-cell depletion and a short course of cyclosporine A (CyA), referred to as “ITC”. Strikingly, GVHD is not observed in engrafted animals despite infusion of an enormous number of donor T cells (>5 x 109 T cells/kg) with the initial HCT. Preliminary data demonstrate that regulatory mechanisms play an important role in preventing GVHD and may facilitate engraftment and tolerance in this model. Our data also demonstrate that subsequent DLIs often fails to convert ITC conditioned mixed chimeric swine to full (donor) chimerism. Despite administration of very high numbers of T-cells (5 x 107 T-cells/kg), neither GVHD nor an increase of donor chimerism levels in the peripheral blood post-DLI were observed. We hypothesize that very strong regulatory mechanisms persist in ITC conditioned HCT recipients that not only prevent GVHD but also interfere with DLI-mediated increases in donor chimerism. In the current study, we have investigated 2 approaches to overcome this strong immune regulation and facilitate DLI mediated conversion to full donor chimerism. In the first approach, 2 chimeric animals underwent leuko-depletion in an attempt to reduce putative regulatory cell populations in chimeric recipients prior to DLI. Animals receiving leuko-depletion prior to DLI demonstrated a modest increase (~12%) in thymic chimerism at 4 weeks, suggesting some transient effect. However, a sustained increase in peripheral blood chimerism levels was not achieved. As a second approach, we infused a higher DLI dose (>15 x 107 T-cell equivalents/kg). This dose was calculated based on the dose of DLI given to mixed chimeric mice that results in consistent conversion of low-level chimeras to full donor chimerism without GVHD. Following this high-dose DLI, we observed successful conversion to full donor chimerism in all hematopoietic cell lineages (>95%) within 1 month (Figure 1) without the induction of clinically significant GVHD. The recipient of the DLI underwent a gradual period of conversion between 3 and 4 weeks, with the percent chimerism increasing without a corresponding increase in absolute number of donor cells. A transient leukopenia was observed, suggesting that donor cells were killing recipient lymphohematopoietic cells without inducing tissue damage in the classical GVHD target organs. In summary, these experiments demonstrate for the first time in this large animal model conversion from low to full donor chimerism without GVHD using high-dose DLI in minimally conditioned recipients of haploidentical HCT. Figure 1: % Chimerism of hematopoietic lineages Figure 1:. % Chimerism of hematopoietic lineages