Evaluation of Per- and Polyfluoroalkyl Substances (PFAS) In Vitro Toxicity Testing for Developmental Neurotoxicity.

Per- and polyfluoroalkyl substances (PFAS) are a diverse set of commercial chemicals widely detected in humans and the environment. However, only a limited number of PFAS are associated with epidemiological or experimental data for hazard identification. To provide developmental neurotoxicity (DNT) hazard information, the work herein employed DNT new approach methods (NAMs) to generate in vitro screening data for a set of 160 PFAS. The DNT NAMs battery was comprised of the microelectrode array neuronal network formation assay (NFA) and high-content imaging (HCI) assays to evaluate proliferation, apoptosis, and neurite outgrowth. The majority of PFAS (118/160) were inactive or equivocal in the DNT NAMs, leaving 42 active PFAS that decreased measures of neural network connectivity and neurite length. Analytical quality control indicated 43/118 inactive PFAS samples and 10/42 active PFAS samples were degraded; as such, careful interpretation is required as some negatives may have been due to loss of the parent PFAS, and some actives may have resulted from a mixture of parent and/or degradants of PFAS. PFAS containing a perfluorinated carbon (C) chain length ≥8, a high C:fluorine ratio, or a carboxylic acid moiety were more likely to be bioactive in the DNT NAMs. Of the PFAS positives in DNT NAMs, 85% were also active in other EPA ToxCast assays, whereas 79% of PFAS inactives in the DNT NAMs were active in other assays. These data demonstrate that a subset of PFAS perturb neurodevelopmental processes in vitro and suggest focusing future studies of DNT on PFAS with certain structural feature descriptors.

Implementation of enhanced recovery protocols reduces opioid use in pediatric laparoscopic cholecystectomy surgery.

PURPOSE: Enhanced recovery protocols [ERPs] standardize care and have been demonstrated to improve surgical quality in adults. We retrospectively compared outcomes before and after implementation of ERPs in children undergoing elective laparoscopic cholecystectomy [ELC] surgery. METHODS: A pediatric-specific ERP was implemented for children undergoing ELC at one [C1] of the two Pediatric Surgical Centers in July 2016. We retrospectively reviewed 606 patients undergoing ELC between July 2014 and December 2019. Of these, 206 patients underwent ELC prior to ERP implementation [Pre-ERP] were compared to 400 patients undergoing ELC managed in the post-ERP implementation period (between January 2017 and December 2019), 21 of which were managed by enhanced recovery protocol. Primary Outcomes included immediate peri-operative and post-operative narcotic use in mean morphine equivalents [MME], narcotics at discharge, complications, nurse calls and returns to system [RTS]. RESULTS: There was a significant decrease in opioid use both post-operatively and at time of discharge in the ERP managed cohort. The MME use during the post-operative period was 0.85 in the in ERP-compliant patients compared to 6.40 in the non-compliant group (p < 0.027). Eighty-six percent of ERP-compliant patients in the study required no narcotics at discharge, which was statistically significant when compared to ERP non-compliant cohort (p < 0.0001). There was also no change in RTS, nurse calls or complications. In addition, in the post-ERP period (2017-2019), a dominant proportion of patients at C1 partially complied with the ERP, resulting in a statistically significantly decrease of opioid use between sites in the post-op period (6.54 vs 10.57 MME) post-ERP (p < 0.001). Similar effects were noted in discharge narcotics. CONCLUSION: The use of pediatric-specific ERP in children undergoing ELC is safe, effective, and provides compassionate pain control while leading to a reduction in opioid use peri-operatively and at discharge. This improvement occurred without changes in RTS, nursing calls or complications. LEVEL OF EVIDENCE: Level III; Retrospective study.

Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis.

OBJECTIVES: To advance our understanding of monogenic forms of intrahepatic cholestasis. METHODS: Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data. RESULTS: Ninety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported. CONCLUSIONS: In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.

Optimal surgical technique in spontaneous pneumothorax: a systematic review and meta-analysis.

BACKGROUND: Numerous thoracoscopic techniques have been used in the management of primary spontaneous pneumothorax (PSP), including wedge resection, pleurectomy, pleural abrasion, chemical pleurodesis, and staple line covering. The purpose of this systematic review was to compare outcomes for the most commonly reported techniques. MATERIALS AND METHODS: A systematic literature search looking at pneumothorax recurrence rate, length of stay, and chest tube duration after surgery was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed database. RESULTS: Fifty-one unique studies comprised of 6907 patients published between January 1988 and June 2015 were identified. Heterogeneity among effect sizes was significant for all outcomes. The lowest recurrence rates were observed in the wedge resection + chemical pleurodesis (1.7%; 95% confidence interval [CI], 1.0%-2.7%) and the wedge resection + pleural abrasion + chemical pleurodesis (2.8%; 95% CI, 1.7%-4.7%) groups. The shortest chest tube duration and length of stay were observed in the wedge resection + staple line covering ± other group (2.1 d; 95% CI, 1.4-2.9 and 3.3 d; 95% CI, 2.6-4.0, respectively). CONCLUSIONS: The variability in reported outcomes and the lack of published multicenter randomized controlled trials highlights a need for more robust investigations into the optimal surgical technique in the management of PSP. Based on the limited quality studies available, this systematic review favors wedge resection + chemical pleurodesis and wedge resection + pleural abrasion + chemical pleurodesis in terms of recurrence rate after surgery for PSP.

Increased morbidity and mortality in cardiac patients undergoing fundoplication.

BACKGROUND: Infants with congenital cardiac disease (CCD) often require gastrostomy tube placement (GT) and need antireflux procedures, such as fundoplications. Our purpose was to compare morbidity/mortality rates among infants with CCD undergoing GT, fundoplication, or both. METHODS: Using the NSQIP-Pediatric, we identified 4070 patients <1-year-old who underwent GT and/or fundoplication from 2012 to 2014. 2346 infants (58%) had CCD categorized as minor, major or severe. Regression models were used to estimate the association of CCD with morbidity/mortality. RESULTS: Among all patients undergoing fundoplication, there were increased odds of morbidity/mortality among CCD patients compared to non-CCD patients (OR 2.15; p < 0.001). Odds of complications decreased when procedures were performed laparoscopically or later in the first year of life. Using GT alone as a reference, fundoplication alone (OR 1.67; p < 0.001) and GT with fundoplication (OR 1.82; p < 0.001) had increased odds of morbidity/mortality among cardiac patients. Increased risk persisted after stratification by severity of CCD and after accounting for surgical approach. CONCLUSION: Fundoplication is associated with increased odds of morbidity/mortality in infants with CCD compared to GT alone. Risks are lower with laparoscopic approach and if surgery is delayed until later in the first year of life. Timing and surgical approach for patients with CCD requires further investigation.

Temporal variability of pyrethroid metabolite levels in bedtime, morning, and 24-h urine samples for 50 adults in North Carolina.

Pyrethroid insecticides are widely used to control insects in both agricultural and residential settings worldwide. Few data are available on the temporal variability of pyrethroid metabolites in the urine of non-occupationally exposed adults. In this work, we describe the study design and sampling methodology for the Pilot Study to Estimate Human Exposures to Pyrethroids using an Exposure Reconstruction Approach (Ex-R study). Two major objectives were to quantify the concentrations of several pyrethroid metabolites in bedtime, first morning void (FMV), and 24-h urine samples as concentration (wet weight), specific-gravity (SG) corrected, creatinine (CR) corrected, and excretion rate values for 50 Ex-R adults over a six-week monitoring period and to determine if these correction approaches for urine dilution reduced the variability of the biomarker levels. The Ex-R study was conducted at the United States Environmental Protection Agency's Human Studies Facility in Chapel Hill, North Carolina USA and at participants' homes within a 40-mile radius of this facility. Recruitment of participants and field activities occurred between October 2009 and May 2011. Participants, ages 19-50 years old, provided daily food, activity, and pesticide-use diaries and collected their own urine samples (bedtime, FMV, and 24-h) during weeks 1, 2, and 6 of a six-week monitoring period. A total of 2503 urine samples were collected from the study participants. These samples were analyzed for the pyrethroid metabolites 3-phenoxybenzoic acid (3-PBA), cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis/trans-DCCA), and 2-methyl-3-phenylbenzoic acid (MPA) using high performance liquid chromatography/tandem mass spectrometry. Only 3-PBA was frequently detected (>50%) in the adult urine samples. Median urinary 3-PBA levels were 0.88 ng/mL, 0.96 ng/mL-SG, 1.04 ng/mg, and 1.04 ng/min for concentration, SG-corrected, CR-corrected, and excretion rate values, respectively, across all urine samples. The results showed that median urinary 3-PBA concentrations were consistently the lowest in FMV samples (0.77 ng/mL, 0.68 ng/mL-SG, 0.68 ng/mg, and 0.58 ng/min) and the highest in 24-h samples (0.92 ng/mL, 1.06 ng/mL-SG, 1.18 ng/mg, and 1.19 ng/min) across all four methods. Intraclass correlation coefficient (ICC) estimates for 3-PBA indicated poor reproducibility (<0.22) for all urine sample types and methods over a day, week, and six weeks. Correcting for urine sample dilution, based on either SG, CR or urine output, introduced additional measurement variability both between- and within-individuals. These results indicate that a single measure of urinary 3-PBA was not sufficient to characterize average exposure regardless of sample type, correction method, and time frame of collection. In addition, the study results can be used to inform the design of exposure characterization strategies in relevant environmental epidemiology studies in the future.

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis.

Enteritis caused by Clostridium difficile toxin (Tx) is a nosocomial disease of increasing clinical concern, but the local mediators of C. difficile TxA inflammation are unknown. The potent vasodilator calcitonin gene-related peptide mediates neurogenic inflammation via the calcitonin receptor-like receptor (CLR). Here we examined the ileum-specific effects of reducing CLR on TxA ileitis by local preinjection of double-stranded RNAs. Treatment with CLR dsRNA for 7 d decreased CLR immunoreactivity, whereas treatment with non-CLR dsRNA did not. Subsequent injection of TxA in the same location increased CLR in rats treated with non-CLR dsRNA but not in rats treated with CLR dsRNA, documenting that local injection of dsRNA is effective in preventing the increase in CLR immunoreactivity in response to local TxA. After non-CLR dsRNA pretreatment, TxA induced robust intestinal secretion, myeloperoxidase activity, and histopathologic indications of inflammation including epithelial damage, congestion, neutrophil infiltration, loss of mucin from goblet cells, and increase in mast cell numbers. After CLR dsRNA pretreatment, TxA-induced changes in intestinal secretion and histopathologic inflammation were improved, including normal mucin staining and fewer resident mast cells. Loss of CLR prevented TxA-mediated activation of NF-κB and concomitant increases in pERK1/2 and TNF-α mRNA. Locally produced CLR plays a proinflammatory role in TxA ileitis via MAPK signaling and TNF-α. The results reported here strongly suggest that a local injection of dsRNA targeting CLR could be an effective local therapeutic approach at the inflammation site in the treatment of a growing, clinically relevant hospital-acquired disease, C. difficile infection.

Indoor residence times of semivolatile organic compounds: model estimation and field evaluation.

Indoor residence times of semivolatile organic compounds (SVOCs) are a major and mostly unavailable input for residential exposure assessment. We calculated residence times for a suite of SVOCs using a fugacity model applied to residential environments. Residence times depend on both the mass distribution of the compound between the "mobile phase" (air and dust particles settled on the carpet) and the "non-mobile phase" (carpet fibers and pad) and the removal rates resulting from air exchange and cleaning. We estimated dust removal rates from cleaning processes using an indoor-particle mass-balance model. Chemical properties determine both the mass distribution and relative importance of the two removal pathways, resulting in different residence times among compounds. We conducted a field study after chlorpyrifos was phased out for indoor use in the United States in 2001 to determine the decreases in chlorpyrifos air concentrations over a one-year period. A measured average decrease of 18% in chlorpyrifos air concentrations indicates the residence time of chlorpyrifos is expected to be 6.9 years and compares well with model predictions. The estimates from this study provide the opportunity to make more reliable estimates of SVOCs exposure in the indoor residential environment.

Noniatrogenic neonatal gastric perforation: the role of interstitial cells of Cajal.

Noniatrogenic neonatal gastric perforation is a rare and life-threatening condition whose etiology is often unclear. Interstitial cells of Cajal act as gastrointestinal pacemaker cells and express the proto-oncogene c-Kit. Six new cases were identified at our institution which presented with no mechanical, pharmacologic, or otherwise medical-related intervention prior to rupture. The number of interstitial cells of Cajal in nonnecrotic muscularis propria from five random high-power fields per specimen was compared using immunohistochemical stains for c-Kit. The authors show that a lack of interstitial cells of Cajal in the stomach musculature may be implicated in the development of noniatrogenic gastric perforation (p = 0.008). Further large-scale studies, including molecular and genetic analysis, may help to better understand this phenomenon.

Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.

Concern over per- and polyfluoroalkyl substances (PFAS) has increased as more is learned about their environmental presence, persistence, and bioaccumulative potential. The limited monitoring, toxicokinetic (TK), and toxicologic data available are inadequate to inform risk across this diverse domain. Here, 73 PFAS were selected for in vitro TK evaluation to expand knowledge across lesser-studied PFAS alcohols, amides, and acrylates. Targeted methods developed using gas chromatography-tandem mass spectrometry (GC-MS/MS) were used to measure human plasma protein binding and hepatocyte clearance. Forty-three PFAS were successfully evaluated in plasma, with fraction unbound (fup) values ranging from 0.004 to 1. With a median fup of 0.09 (i.e., 91% bound), these PFAS are highly bound but exhibit 10-fold lower binding than legacy perfluoroalkyl acids recently evaluated. Thirty PFAS evaluated in the hepatocyte clearance assay showed abiotic loss, with many exceeding 60% loss within 60 min. Metabolic clearance was noted for 11 of the 13 that were successfully evaluated, with rates up to 49.9 µL/(min × million cells). The chemical transformation simulator revealed potential (bio)transformation products to consider. This effort provides critical information to evaluate PFAS for which volatility, metabolism, and other routes of transformation are likely to modulate their environmental fates.

Successful Medical-Surgical Management of Intracardiac Thrombosis and Pulmonary Pseudoaneurysms in an Adolescent With Hughes-Stovin Syndrome.

We present an adolescent male with a single intracardiac mass and pulmonary emboli, complicated by peripheral venous thrombosis and subsequent development of pulmonary pseudoaneurysms, leading to diagnosis of Hughes-Stovin syndrome. Remission was achieved with cyclophosphamide, corticosteroids, and pseudoaneurysm resection and maintained with infliximab and methotrexate.

Proteus syndrome: three case reports with a review of the literature.

Proteus syndrome (PS) is a rare, progressive disorder that manifests as asymmetric, disproportionate overgrowth affecting tissues derived from any germline layer. Cases of PS from 2005-2010 were retrieved from the pathology files at our institution. Two confirmed cases and one possible case of PS were identified. All patients came from different ethnic backgrounds. Patient 1 displayed classic skin and overgrowth lesions. Patient 2 displayed various features, particularly vascular malformations. Patient 3 demonstrated a cerebriform connective tissue nevus alone. These patients demonstrate the spectrum of presentations of PS. Much is left to learn about this disfiguring disease.

Impedance planimetry (EndoFLIP) assisted laparoscopic esophagomyotomy in pediatric population.

INTRODUCTION: Functional lumen imaging probe (EndoFLIP) is a diagnostic technology that assesses esophageal cross-sectional area via impedance planimetry during controlled volumetric distention. The purpose of this study is to evaluate the utility of EndoFLIP intraoperatively during laparoscopic esophagomyotomy. METHODS: We performed a retrospective cohort study reviewing all patients undergoing EndoFLIP assisted laparoscopic esophagomyotomy for achalasia between January and December 2021 (n = 10). Twenty-two patients with achalasia that underwent traditional laparoscopic esophagomyotomy between July 2014 and September 2019 served as a comparison. Primary outcome evaluated was resolution of symptoms at discharge. Secondary outcomes included change in distensibility index (DI), operative time, length of stay, time to regular diet, and reinterventions. RESULTS: All patients managed with EndoFLIP assistance had resolution of dysphagia and postprandial vomiting following intervention. Mean change in DI was 5.32 mm2/mmHg with a myotomy length of 3.6 cm. Operative time was shorter in the EndoFLIP cohort (97 min versus 185 min, p = <0.001). Study patients did not undergo an antireflux operation. There was no difference in length of stay or time to soft diet between groups. All patients were discharged on postoperative day 1 tolerating a mechanical soft diet. No acid suppressive medications were prescribed during the observation period. One patient required dilation for recurrent symptoms and one required reoperation for mucosal leak. CONCLUSION: EndoFLIP assisted laparoscopic esophagomyotomy results in similar short-term outcomes to traditional surgical technique. EndoFLIP allows for focused myotomy length and a shorter operative time. LEVEL OF EVIDENCE: III.

Implementation of enhanced recovery protocols reduces opioid use in pediatric laparoscopic Heller myotomy surgery.

BACKGROUND: Enhanced recovery protocols (ERPs) are effective means of standardizing and improving the quality of surgical care in adults. Our purpose was to retrospectively compare outcomes before and after implementation of ERPs in children undergoing laparoscopic Heller myotomy for achalasia. METHODS: A pediatric-specific ERP was used for children undergoing laparoscopic Heller myotomy starting July 2017 at two pediatric surgery centers within a single metropolitan healthcare system. A retrospective review of 8 patients undergoing Heller myotomies between July 2014 and July 2017 was performed as a control. This cohort was compared to 14 patients managed post-ERP implementation (2017-2020). Outcomes of interest investigated included opioid use during admission, narcotics at discharge, time to regular diet, length of stay (LOS), and readmissions. RESULTS: There was a significant decrease in opioid use both while in the hospital and at time of discharge. Mean morphine equivalent use was 4.50 mg in the pre-ERP cohort and 1.97 mg in the post-ERP cohort. Furthermore, 8 out of 14 (57%) patients in the post-ERP cohort received no opioids during the admission compared with only 2 out of 8 (25%) patients in the pre-ERP cohort. Only 1 out of 14 (7.14%) patients in the post-ERP cohort was discharged with a prescription for opioid medication while 6 out of 8 (75%) in the pre-ERP cohort were discharged with an opiate prescription. CONCLUSIONS: The use of ERP in children undergoing laparoscopic Heller myotomy surgery is safe and effective and leads to a reduction in opioid use during admission and at discharge. LEVELS OF EVIDENCE: Level III.

Dual Balloon Catheter: A Novel Laparoscopic Common Bile Duct Exploration Device.

Introduction: Choledocholithiasis is a disease process that can be managed by laparoscopic common bile duct exploration at the time of cholecystectomy. However, it can be negatively perceived by surgeons as lengthening procedure time and adding technical complexity. Materials and Methods: We have created a dual balloon biliary intervention catheter designed to make common duct exploration efficient, simple, and safe. The device consists of two balloons, one compliant and one noncompliant, to perform initial cholangiography, dilate the sphincter, and occlude the proximal duct for distal power flushing of stones. The catheter design facilitates a stepwise, over the wire progression of interventions with a singular device. Results: The catheter has been successfully deployed in a porcine feasibility model and the dual balloon concepts reduced to practice using currently available devices. Conclusion: Laparoscopic common bile duct exploration is a safe and effective way to treat choledocolithiasis. The Dual Balloon Catheter is a novel device that allows for duct occlusion for cholangiogram and power flushing in conjunction with duct and sphincter dilation.

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B (PHOX2B) gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness. CCHS is a lifelong disorder. Patients require assisted ventilation throughout their life delivered by positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and/or diaphragm pacing. At different ages, patients may prefer to change their modality of assisted ventilation. This requires an individualized and coordinated multidisciplinary approach. Additional clinical features of CCHS that may present at different ages and require periodic evaluations or interventions include Hirschsprung's disease, gastrointestinal dysmotility, neural crest tumors, cardiac arrhythmias, and neurodevelopmental delays. Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist, and respiratory therapist. A comprehensive multidisciplinary approach may optimize care and improve patient outcomes. With advances in CCHS management strategies, there is prolongation of survival necessitating high-quality multidisciplinary care for adults with CCHS.

Urocortin 1 modulates immunosignaling in a rat model of colitis via corticotropin-releasing factor receptor 2.

Urocortins (UCNs) and their receptors are potent immunoregulators in the gastrointestinal (GI) tract, where they can exert both pro- and anti-inflammatory effects. We examined the contribution of Ucn1 and its receptors to the pathogenesis, progression, and resolution of colitis. Trinitrobenzene sulfonic acid was used to induce colitis in rats. Ucn1 mRNA and immunoreactivity (IR) were ubiquitously expressed throughout the GI tract under basal conditions. During colitis, Ucn1 mRNA levels fell below basal levels on day 1 then increased again by day 6, in association with an increase in the number of Ucn1-IR inflammatory cells. Ucn1-IR cells were also numerous in proliferating granulation tissue. In contrast to Ucn1 expression, average phosphorylated ERK1/2 (pERK1/2) expression rose above controls levels on day 1 and was very low on day 6 of colitis. Knockdown of corticotropin-releasing factor 2 (CRF(2)) but not CRF(1) by RNA interference during colitis significantly decreased the macroscopic lateral spread of ulceration compared with uninjected controls or animals with CRF(1) knockdown. After knockdown of CRF(2), but not of CRF(1) during colitis, edema resolution assessed microscopically was slowed, and myeloperoxidase activity remained elevated even at day 6. Ucn1 and TNF-α mRNA peaked earlier, whereas pERK1/2 activation was attenuated after CRF(2) knockdown. Thus we conclude that local CRF(2) and pERK1/2 activation is pivotal for macroscopic spread of colitis and resolution of edema. Elimination of CRF(2), but not CRF(1), results in uncoordinated immune and pERK1/2 signaling responses.

Assessing the quantitative relationships between preschool children's exposures to bisphenol A by route and urinary biomonitoring.

Limited published information exists on young children's exposures to bisphenol A (BPA) in the United States using urinary biomonitoring. In a previous project, we quantified the aggregate exposures of 257 preschool children to BPA in environmental and personal media over 48-h periods in 2000-2001 at homes and daycares in North Carolina and Ohio. In the present study for 81 Ohio preschool children ages 23-64 months, we quantified the children's urinary total BPA (free and conjugated) concentrations over these same 48-h periods in 2001. Then, we examined the quantitative relationships between the children's intakes doses of BPA through the dietary ingestion, nondietary ingestion, and inhalation routes and their excreted amounts of urinary BPA. BPA was detected in 100% of the urine samples. The estimated median intake doses of BPA for these 81 children were 109 ng/kg/day (dietary ingestion), 0.06 ng/kg/day (nondietary ingestion), and 0.27 ng/kg/day (inhalation); their estimated median excreted amount of urinary BPA was 114 ng/kg/day. Our multivariable regression model showed that dietary intake of BPA (p = 0.04) and creatinine concentration (p = 0.004) were significant predictors of urinary BPA excretion, collectively explaining 17% of the variability in excretion. Dietary ingestion of BPA accounted for >95% of the children's excreted amounts of urinary BPA.

Exposure to Triclosan and Bisphenol Analogues B, F, P, S and Z in Repeated Duplicate-Diet Solid Food Samples of Adults.

Triclosan (TCS) and bisphenol analogues are used in a variety of consumer goods. Few data exist on the temporal exposures of adults to these phenolic compounds in their everyday diets. The objectives were to determine the levels of TCS and five bisphenol analogues (BPB, BPF, BPP, BPS, and BPZ) in duplicate-diet solid food (DDSF) samples of adults and to estimate maximum dietary exposures and intake doses per phenol. Fifty adults collected 776 DDSF samples over a six-week monitoring period in North Carolina in 2009-2011. The levels of the target phenols were concurrently quantified in the DDSF samples using gas chromatography/mass spectrometry. TCS (59%), BPS (32%), and BPZ (28%) were most often detected in the samples. BPB, BPF, and BPP were all detected in <16% of the samples. In addition, 82% of the total samples contained at least one target phenol. The highest measured concentration of 394 ng/g occurred for TCS in the food samples. The adults' maximum 24-h dietary intake doses per phenol ranged from 17.5 ng/kg/day (BPB) to 1600 ng/kg/day (TCS). An oral reference dose (300,000 ng/kg/day) is currently available for only TCS, and the adult's maximum dietary intake dose was well below a level of concern.