Racial disparities affect the association between gestational urinary phthalate mixtures and infant genital measures.

Background: Phthalates are ubiquitous anti-androgenic endocrine disrupting chemicals found in personal care products, medications, and many plastics. Studies have shown a racial disparity in phthalates exposure among U.S. women, which may also impact fetal development. Methods: We conducted a prospective cohort study of gestational exposure to a phthalates mixture in a racially-diverse population to determine their association with genital development. Mid-gestation (18-22 weeks) urine was collected from 152 women who self-identified as non-Hispanic Black and 158 women who self-identified as non-Hispanic White in Charleston, South Carolina between 2011 and 2014. We measured eight phthalate monoester metabolites in urine using liquid chromatography tandem-mass spectrometry. Mid-gestational penile dimensions were measured using ultrasound and anogenital distances were measured postnatally. We used Bayesian kernel machine regression to estimate the associations among the mixture of phthalate metabolites and mid-gestation penile dimensions and postnatal anogenital distance measures among singleton male (n = 179) and female (n = 131) infants, adjusted for urinary specific gravity, maternal age, body mass index, education level, cigarette smoking, and gestational age at enrollment or birth weight z-score. Results: We found a stronger association between greater phthalates and decreased anopenile distance among infants born to women who self-identified as Black. Mono (2-ethylhexyl) phthalate (MEHP) was the driving mixture component among Black women, and monobutyl phthalate (MBP) and monoethyl phthalate (MEP) were drivers among White women. We also identified a non-linear association between phthalates and lesser ultrasound penile volume among women who self-identified as Black with monoisobutyl phthalate (MiBP) and MBP being most important. We also found an association between greater phthalates and shorter anoclitoral distance among infants born to women who self-identified as Black, with MEP and monobenzyl phthalate (MBzP) contributing most to this association. Conclusion: Our results suggest a disparity in the association between gestational exposure to a mixture of phthalates and fetal genital development among women who self-identified as Black compared to White.

Understanding factors influencing primary treatment with intradetrusor onabotulinumtoxinA versus augmentation cystoplasty in patients with spina bifida.

PURPOSE: Surgical interventions in the urologic management of children with neurogenic bladder secondary to spina bifida aim to preserve upper tract function, prevent urinary tract infections, and optimize quality of life. However, since the introduction of intravesical onabotulinumtoxinA (Botox) in the management of these patients, the indications for choosing Botox over augmentation cystoplasty (AC) remain undefined. The objective of this study was to determine which factors lead patients to undergo Botox versus AC as a primary surgical treatment after failing medical management. METHODS: We retrospectively reviewed the records of pediatric patients with myelomeningocele undergoing either primary Botox or primary AC at our institution between 2013 and 2018. We recorded demographic and clinical information. We identified 10 important clinical decision-making factors: bladder trabeculation, vesicoureteral reflux, or hydronephrosis on imaging; end-filling pressure (EFP) ≥40 cm H2O, detrusor overactivity, detrusor-sphincter dyssynergia, or reduced capacity on urodynamic studies; physician-perceived bladder hostility; and patient/family desire for continence and independence. The presence of these factors was compared between patients undergoing either primary Botox or primary AC. RESULTS: We identified 14 and 50 myelomeningocele patients who underwent primary AC and primary Botox, respectively. We found no significant differences in age, sex, race, or history of reconstructive surgery (antegrade continence enema or catheterizable channel). For the 10 decision-making factors, desire for independence/continence (p = <0.001) and reduced capacity (p = 0.002) were significantly associated with AC, while trabeculation (p = 0.006), EFP ≥40 cm H2O (p = 0.029), rising slope (p = 0.019), and physician-perceived hostility (p = 0.012) were significantly more common with Botox. CONCLUSIONS: At our institution, quality of life measures prompted AC over objective urodynamic or imaging findings before attempting Botox. These findings support a shared decision-making approach when considering surgical intervention for neurogenic bladder secondary to myelomeningocele.

BDNF guides neural stem cell-derived axons to ventral interneurons and motor neurons after spinal cord injury.

Neural stem cells (NSCs) implanted into sites of spinal cord injury (SCI) extend very large numbers of new axons over very long distances caudal to the lesion site, and support partial functional recovery. Newly extending graft axons distribute throughout host gray and white matter caudal to the injury. We hypothesized that provision of trophic gradients caudal to the injury would provide neurotrophic guidance to newly extending graft-derived axons to specific intermediate and ventral host gray matter regions, thereby potentially further improving neural relay formation. Immunodeficient rats underwent C5 lateral hemisection lesions, following by implants of human NSC grafts two weeks later. After an additional two weeks, animals received injections of AAV2-BDNF expressing vectors three spinal segments (9 mm) caudal to the lesion in host ventral and intermediate gray matter. After 2 months additional survival, we found a striking, 5.5-fold increase in the density of human axons innervating host ventral gray matter (P < 0.05) and 2.7-fold increase in intermediate gray matter (P < 0.01). Moreover, stem cell-derived axons formed a substantially greater number of putative synaptic connections with host motor neurons (P < 0.01). Thus, trophic guidance is an effective means of enhancing and guiding neural stem cell axon growth after SCI and will be used in future experiments to determine whether neural relay formation and functional outcomes can be improved.

Design and evaluation of poly-nitrogenous adjuvants capable of potentiating antibiotics in Gram-negative bacteria.

Antibiotic resistance has been a growing public health crisis since the 1980s. Therefore, it is essential not only to continue to develop novel antibiotics but also to develop new methods for overcoming resistance mechanisms in pathogenic bacteria so antibiotics can be reactivated towards these resistant strains. One common cause of antibiotic resistance in Gram-negative bacteria is reduced permeability of the tightly packed, negatively charged lipopolysaccharide outer membrane (OM), which dramatically reduces or even prevents antibiotic accumulation within the cell. Adjuvants that promote passive diffusion through the OM, including phenylalanine-arginine-ß-naphthylamide, tobramycin, and pentamidine, have proven useful in potentiating antibiotics against Gram-negative bacteria. Structural evaluation of these adjuvants, which all include multiple nitrogenous groups, indicates that the entry rules developed for improving antibiotic accumulation in Escherichia coli (EC), could also be used to guide adjuvant development. To this end, a series of structurally simple poly-nitrogenous diphenylsuccinamide compounds have been prepared and evaluated for their ability to potentiate a panel of classic antibiotics in wild-type EC and Pseudomonas aeruginosa (PA). Modest adjuvant activity was observed for all compounds surveyed when co-administered with known antibiotics to inhibit either wild-type EC or PA, and all were able to accumulate in both EC and PA.

Increasing utilization of the TWIST score in workup of patients with acute scrotal pain: Role in diagnosis and risk stratification.

INTRODUCTION: The TWIST score is a 5-component physical examination score used to aid in diagnosis of testicular torsion (TT) and could lessen need for radiologic testing in certain clinical scenarios. OBJECTIVE: TWIST use was not previously widespread at our institution. The primary objective of this quality improvement study was to achieve 100% compliance in TWIST utilization among urology and ED residents and to assess for score concordance between ED and urology assessments. Secondary goals were correlation of TWIST components with need for orchiectomy. METHODS: ED staff were educated about the TWIST score and asked to complete assessment for patients presenting with acute scrotal pain. Simultaneously, an electronic medical record-based dot phrase was introduced for urology trainees to complete an independent TWIST evaluation. Spearman correlation was performed to assess association between ED and Urology TWIST scores. Multivariable logistic regression was performed to assess association of TWIST score components and need for orchiectomy. RESULTS: 103 patients presented to the ED from 3/2018-11/2020 with a complaint of acute scrotal pain; 47 were diagnosed with torsion. As compared to our retrospective cohort, the documentation rate of complete TWIST score components on exam rose from 9% to 98% (P < 0.001) on ED evaluation and 16%-66% on urology evaluation (P < 0.001). Rates of repeat ultrasound for patient's transferred between facilities was similar (58% vs. 63%; p = 0.66) as was median time to OR (160 min vs. 145 min; p = 0.5). Using TWIST cutoff of >5 yielded a specificity of 94.5% for diagnosis of torsion, with corresponding strong correlation between ED and urology scores (rho = 0.71). A firm testicle was noted on urology evaluation in 100% of orchiectomy patients (vs. 61% of salvage patients) with persistent association after controlling for duration of symptoms (OR 28.1; P = 0.016). DISCUSSION: Through two-pronged quality improvement efforts, we significantly improved utilization of the TWIST score by ED and urology staff for workup of patients with acute testicular pain. We confirmed the high sensitivity and specificity of the TWIST score and demonstrated inter-rater reliability between ED and urology assessments. On prospective analysis, testicular firmness on exam was predictive of need for orchiectomy. CONCLUSION: The TWIST score is an accurate diagnostic tool for both ED and urology providers in workup of children with acute scrotal pain, with a normal score essentially ruling out the condition. Future work should aim at minimizing unnecessary testing in patients demonstrated to be at high risk for torsion.

Rhesus macaque versus rat divergence in the corticospinal projectome.

We used viral intersectional tools to map the entire projectome of corticospinal neurons associated with fine distal forelimb control in Fischer 344 rats and rhesus macaques. In rats, we found an extraordinarily diverse set of collateral projections from corticospinal neurons to 23 different brain and spinal regions. Remarkably, the vast weighting of this "motor" projection was to sensory systems in both the brain and spinal cord, confirmed by optogenetic and transsynaptic viral intersectional tools. In contrast, rhesus macaques exhibited far heavier and narrower weighting of corticospinal outputs toward spinal and brainstem motor systems. Thus, corticospinal systems in macaques primarily constitute a final output system for fine motor control, whereas this projection in rats exerts a multi-modal integrative role that accesses far broader CNS regions. Unique structural-functional correlations can be achieved by mapping and quantifying a single neuronal system's total axonal output and its relative weighting across CNS targets.

Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race.

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women's reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; p < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; p < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; p < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.

Prenatal Repair and Physical Functioning Among Children With Myelomeningocele: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The Management of Myelomeningocele Study (MOMS), a randomized clinical trial of prenatal vs standard postnatal repair for myelomeningocele, found that prenatal repair reduced hydrocephalus and hindbrain herniation and improved motor function in children aged 12 to 30 months. The Management of Myelomeningocele Study Follow-up (MOMS2) was conducted in children at ages 5 to 10 years. The primary (neurocognitive) outcome has already been reported. Objective: To determine whether MOMS2 participants who had prenatal repair have better physical functioning than those with postnatal repair. Design, Setting, and Participants: Participants from MOMS were recruited for participation in the follow-up study, MOMS2, conducted from April 9, 2012, to April 15, 2017. For this secondary analysis of the randomized clinical trial, trained examiners without knowledge of the treatment group evaluated the physical characteristics, self-care skills, neurologic function, and mobility of the children. Physical functioning outcomes were compared between the prenatal and postnatal repair groups. MOMS2 was conducted at the same 3 clinical sites as MOMS. Home visits were conducted for families who were unable to travel to one of the clinical sites. Of the 161 children with myelomeningocele aged 5 to 10 years old enrolled in MOMS2, 154 had a physical examination and were included in the analyses. Exposures: Prenatal repair of myelomeningocele. Main Outcomes and Measures: Prespecified secondary trial outcomes of self-care skills, functional mobility, walking skills, and motor level. Results: This analysis included 78 children with postnatal repair (mean [SD] age, 7.4 [2.1] years; 50 girls [64.1%]; 69 White children [88.5%]) and 76 with prenatal repair (mean [SD] age, 7.5 [1.2] years; 43 boys [56.6%]; 70 White children [92.1%]). Children in the prenatal repair group were more competent with self-care skills (mean [SD] percentage of maximum FRESNO Scale score, 90.8% [9.6%] vs 85.5% [17.6%]) and were commonly community ambulators per the Modified Hoffer Classification (51.3% prenatal vs 23.1% postnatal; adjusted relative risk [aRR] for sex, 1.70; 95% CI, 1.23-2.34). Children with prenatal repair also performed the 10-m walk test 1 second faster (difference in medians, 1.0; 95% CI, 0.3-1.7), had better gait quality (adjusted mean difference for home distances of 5 m, 1.71; 95% CI, 1.14-2.54), and could perform higher-level mobility skills (adjusted mean difference for motor total, 5.70; 95% CI, 1.97-11.18). Children in the prenatal repair group were less likely to have a motor function level worse than their anatomic lesion level (aRR, 0.44; 95% CI, 0.25-0.77). Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that the physical functioning benefits of prenatal repair for myelomeningocele reported at age 30 months persisted into school age. These findings indicate the benefit of prenatal repair of myelomeningocele for school-aged children. Trial Registration: ClinicalTrials.gov Identifier: NCT00060606.

Association between gestational phthalate exposure and newborn head circumference; impacts by race and sex.

Observational and experimental studies report associations between gestational phthalate exposure and fetal development, yet few data exist to characterize phthalate effects on head circumference (HC) or to estimate the impact of race or sex. To address this data gap, we enrolled 152 African American and 158 white mothers with uncomplicated singleton pregnancies from the Charleston, South Carolina (USA) metropolitan area in a prospective birth cohort. Study participants provided up to two urine specimens during mid and late gestation, completed a study questionnaire, and allowed access to hospital birth records. We measured eight phthalate monoester metabolites using liquid chromatography with tandem mass spectrometry, and calculated molar sums of phthalate parent diesters. After specific gravity correction, we tested for associations between phthalates and neonatal HC (cm) and cephalization index (cm/g) using multiple informant linear regression with inverse probability weighting to account for selection bias between repeated urine sampling, adjusted for maternal race, age, body mass index, education, and smoking. We explored interactions by maternal race and infant sex. A doubling of urinary monoethyl phthalate (MEP) concentration was associated with a -0.49% (95%CI: -0.95%, -0.02%) smaller head circumference, although seven other phthalate metabolites were null. There were no statistically significant associations with cephalization index. HC was larger for whites than African American newborns (p < 0.0001) but similar for males and females (p = 0.16). We detected interactions for maternal race with urinary monobutyl phthalate (MBP; p = 0.03), monobenzyl phthalate (MBzP; p = 0.01), monoethylhexyl phthalate (MEHP; p = 0.05), monomethyl phthalate (MMP; p = 0.02), and the sum of dibutyl phthalate metabolites (∑DBP; p = 0.05), in which reduced HC circumference associations were stronger among whites than African Americans, and interactions for sex with MBP (p = 0.08) and MiBP (p = 0.03), in which associations were stronger for females than males. Our results suggest that gestational phthalate exposure is associated with smaller neonatal HC and that white mothers and female newborns have greater susceptibility.

Biomonitoring of emerging DINCH metabolites in pregnant women in charleston, SC: 2011-2014.

Due to the mounting evidence that phthalates, specifically di-2-ethylhexyl phthalate and dibutyl phthalate, produce adverse endocrine effects in humans and wildlife, the use of other chemicals as replacements has increased. One of the most commonly encountered phthalate replacements is di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH). Currently, little is known about the prevalence of human exposure, bioactivity, and endocrine disrupting potential of DINCH. We sampled urine from 100 pregnant women during the second trimester of pregnancy living in Charleston, SC between 2011 and 2014 and measured the following DINCH metabolites by LC-MS/MS: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH), cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (oxo-MINCH), and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (cx-MINCH). These metabolites were also tested on human estrogen receptor alpha and progesterone receptor beta transactivation assays in vitro. OH-MINCH was detected in 98% of urine samples. The specific gravity-adjusted median (interquartile range) OH-MINCH concentration was 0.20 (0.25) ng/mL, and concentrations were significantly higher in African American women compared to Caucasian women (p = 0.01). DINCH metabolite concentrations were consistent between years, and they did not exhibit estrogenic or progestogenic activity in vitro. Human exposure to these emerging compounds should continue to be monitored, especially in vulnerable populations, to ensure the replacement of phthalates by DINCH is not a case of regrettable substitution.

Prenatal Repair of Myelomeningocele and School-age Functional Outcomes.

BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9-10.3 years) between prenatal versus postnatal surgery groups. METHODS: Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. RESULTS: The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002). CONCLUSIONS: There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.

Fetal repair of myelomeningocele: current status and urologic implications.

Over the last 40 years, vast changes have occurred in the care of children with open neural tube defects. Not only has newborn survival dramatically improved but survival into adulthood has improved as well. Now, the ability to accurately identify and repair myelomeningocele (MMC) lesions before birth has become a reality. Pioneering efforts at several institutions in the United States paved the way for such advancements in care. Substantial data now exist to support the positive benefits of fetal MMC repair from a neurosurgical standpoint, chiefly the significant reduction in hindbrain herniation, decrease in shunt-dependent hydrocephalus, and improvement in lower-extremity motor function. However, until only recently, the urological impact of fetal repair has not been nearly as positive overall. Multiple retrospective reports of newborn bladder function from the United States suggest that prenatal repair has provided neither short-term nor long-term improvements in bladder function. Yet, the retrospective nature of these data and their focus upon urodynamic studies (UDS) parameters have hampered the ability to draw conclusions. Recently, published data from the landmark Management of Myelomeningocele Study indicate that fetal repair may improve certain aspects of bladder function when compared with conventional repair. This review provides an overview of the history and timeline of fetal repair in the United States and brings the reader quickly up to date on the current impact of repair on both neurosurgical and urological outcomes.

Renal Papillary Mapping and Quantification of Randall's Plaque in Pediatric Calcium Oxalate Stone Formers.

Introduction: Randall's plaque (RP) with attached stones is recognized as a primary mechanism for stone formation in adult calcium oxalate stone formers (CaOx SFs). The role of RP in pediatric stone pathogenesis is unknown, with no reported studies to date. The purpose of this study is to investigate renal papillary abnormalities and quantify RP in pediatric CaOx SFs. Methods: Eight pediatric CaOx SFs underwent ureteroscopy for symptomatic urolithiasis. The collecting system was mapped using a digital ureteroscope. Video for each patient was then reviewed using a retrograde pyelogram to confirm the location of each papilla. A single investigator (N.L.M.) reviewed the video to quantify RP. Each papilla was graded as having mild, moderate, or severe amount of RP. Patient history was recorded. Results: An average of nine papillae were mapped per patient. RP was present in 100% of patients and in 88.8% (64/72) of all papillae examined. When present, RP was uniformly distributed throughout the kidney without preferential distribution to a region or pole. The amount of RP on the papillae was graded as mild in 60%, moderate in 20.8%, and severe in 8.3%. The mean fractional RP coverage ranged from 0.39% to 9.34%. No correlation was found between the amount of plaque and age at first stone episode or number of prior stone episodes (p = 0.84). Attached stones were rare (1/8 patients). The two patients with severe RP had a small amount of calcium phosphate in their stone analysis. Conclusions: RP is common in pediatric CaOx SFs. Compared with adult CaOx SFs wherein up to 75% of stones are found attached to RP, attached stones were rare. The significance of these findings in the pathogenesis of pediatric stone formation remains unclear and will require longer term follow-up.

Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury.

Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection. Four weeks after hemisection, we administered multiple intraparenchymal Chase injections below the lesion, targeting spinal cord circuits that control hand function. Hand function improved significantly in Chase-treated monkeys relative to vehicle-injected controls. Moreover, Chase significantly increased corticospinal axon growth and the number of synapses formed by corticospinal terminals in gray matter caudal to the lesion. No detrimental effects were detected. This approach appears to merit clinical translation in spinal cord injury.

Effect of Prenatal Repair of Myelomeningocele on Urological Outcomes at School Age.

PURPOSE: We investigated longer term urological outcomes in patients enrolled in the Management of Myelomeningocele Study (MOMS). MATERIALS AND METHODS: Women who participated in the original trial were asked for consent for followup for their child at age 6 years or older in a single comprehensive study visit to a MOMS center. Participating children underwent urological and radiologic procedures to provide objective evidence of current bladder functioning. Primary urological outcome was defined as any among need for clean intermittent catheterization, vesicostomy, urethral dilatation or augmentation cystoplasty. RESULTS: A total of 156 children were evaluated, with a mean age of 7.4 years. Overall 62% vs 87% in the prenatal and postnatal surgery groups, respectively, were placed on clean intermittent catheterization (RR 0.71, 95% CI 0.58-0.86, p <0.001). Voiding status was significantly different between the groups (p <0.001) as 24% in the prenatal group vs 4% in the postnatal group (RR 5.8, 95% CI 1.8-18.7) were reported to be voiding volitionally. Augmentation cystoplasty, vesicostomy and urethral dilation did not differ between the 2 groups. Aside from a larger post-void residual urodynamic catheterization volume, there were no other statistical differences in videourodynamic data or findings on renal/bladder ultrasound. CONCLUSIONS: Prenatal closure of myelomeningocele resulted in less reported clean intermittent catheterization at school age and the mechanism for this is unclear. Although most children are in diapers or on clean intermittent catheterization, parental reports showed children who underwent prenatal closure may be more likely to void volitionally than the postnatal group. Despite these findings, urological outcomes alone should not be the sole impetus to perform in utero closure in children with spina bifida.

Prevalence of Eight Phthalate Monoesters in Water from the Okavango Delta, Northern Botswana.

Phthalate diesters are used in personal care products, plastics, and pesticides, resulting in widespread human and wildlife exposure. Phthalate diesters leach out of these products and ultimately enter biological systems where they are quickly metabolized to phthalate monoesters and glucuronides. As such, phthalate monoesters can serve as indicators of anthropogenic activity in wilderness areas. The Okavango Delta, an inland seasonal wetland covering 5000-12,000 km2 in Botswana, provides fresh water to many species of birds, fish, reptiles, and large mammals. Water samples (N = 46) were taken from across the Okavango water system, extracted, and analyzed for eight different phthalate monoesters using liquid chromatography and isotope dilution mass spectrometry. Seven of eight phthalate monoesters were detected from the low ng/L to low µg/L levels. Phthalate monoesters were found in samples from all five sampling regions. Sources of these contaminants are unknown, but their presence indicates encroachment of human activity on the Okavango Delta.

Racial disparity in maternal phthalates exposure; Association with racial disparity in fetal growth and birth outcomes.

Experimental and observational data implicate phthalates as developmental toxicants. However, few data are available to assess the maternal risks of gestational exposure by race and infant sex. To begin to address this data gap, we characterized associations between maternal urinary phthalate metabolites and birth outcomes among African American and white mothers from a southeastern U.S. population. We enrolled pregnant African American (n = 152) and white (n = 158) women with singleton live births between 18 and 22 weeks gestation. We measured phthalate metabolites (mono-n-butyl phthalate (MBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and the sums of DEHP (ΣDEHP) and DBP (ΣDBP) metabolites) in up to two gestational urine specimens from mothers, and evaluated confounder-adjusted associations per natural log unit greater concentration with birth weight for gestational age z-score, small for gestational age (SGA; <10th %tile), preterm birth (PTB; <37 weeks gestation), and low birth weight (LBW; <2500 g). We also tested for interactions by maternal race and infant sex. We found that lower z-scores were associated with greater MiBP (ß = -0.28; 95% CI: -0.54, -0.02) and MMP (ß = -0.30; 95% CI: -0.52, -0.09) concentrations, while MEP interacted with race (p = 0.04), indicating an association among whites (ß = -0.14; 95% CI: -0.28, 0.001) but not among African Americans (ß = 0.05; 95% CI = -0.09, 0.19). Greater MiBP (OR = 2.82; 95% CI: 1.21, 6.56) and MEOHP (OR = 2.80; 95% CI: 1.05, 7.42) were associated with an overall higher SGA risk, greater MEHP was associated with higher SGA risk (p = 0.10) in whites (OR = 3.26 95% CI: 0.64, 16.56) but not in African Americans (OR = 0.71 95% CI: 0.07, 7.17), and the associations for MiBP (p = 0.02) and ΣDBP (p = 0.02) varied by infant sex. We detected interactions for PTB in which African Americans were at higher risk than whites for greater MiBP (p = 0.08) and MEP (p = 0.02) although lower risk for greater MEHP (p = 0.09). Greater MEP was associated with an overall higher LBW risk (OR = 1.33; 95% CI: 0.95, 1.86), and males were at higher risk than females with greater MBP (p = 0.002), MiBP (p = 0.02), MBzP (p = 0.01), MEP (p = 0.002), MMP (p = 0.09), and ΣDBP (p = 0.01) concentrations. Overall, our results suggest that gestational phthalate exposure is associated with adverse maternal birth outcomes, and that the effects vary by maternal race and infant sex.

Prediction of Complications, Readmission, and Revision Surgery Based on Duration of Preoperative Opioid Use: Analysis of Major Joint Replacement and Lumbar Fusion.

BACKGROUND: Preoperative opioid use results in adverse outcomes and higher costs after elective surgery. However, duration thresholds for higher risk are not entirely known. Therefore, the purpose of our study was to determine the number and duration of preoperative opioid prescriptions in order to estimate the risk of postoperative adverse events after major joint replacement and lumbar fusion. METHODS: National insurance claims data (2007 to September 30, 2015) were used to identify primary total knee arthroplasties (TKAs), total hip arthroplasties (THAs), and 1 or 2-level posterior lumbar fusions (PLFs) performed for degenerative disease. The effect of preoperative opioid burden (naive, ≤3 months, >3 to 6 months, >6 months but stopped 3 months before surgery, and >6 months of continuous use) on the risks of various adverse outcomes was studied using Cox proportional hazards analysis with adjustment for demographic and clinical covariates. RESULTS: A total of 58,082 patients stratified into 3 cohorts of 32,667 with TKA, 14,734 with THA, and 10,681 with 1 or 2-level PLF were included for this analysis. A duration of preoperative opioids of >3 months was associated with a higher risk of 90-day emergency department (ED) visits for all causes and readmission after TKA. Preoperative opioid prescription for >6 months was associated with a higher risk of all-cause and pain-related ED visits, wound dehiscence/infection, and hospital readmission within 90 days as well as revision surgery within 1 year after TKA, THA, and PLF. Stopping the opioid prescription 3 months preoperatively for chronic users resulted in a significant reduction in the risk of adverse outcomes, with the greatest impact seen after THA and PLF. CONCLUSIONS: Patients with a preoperative opioid prescription for up to 3 months before a major arthroplasty or a 1 or 2-level lumbar fusion had a similar risk of adverse outcomes as opioid-naive patients. While >6 months of opioid use was associated with a higher risk of adverse outcomes, a 3-month prescription-free period before the surgery appeared to mitigate this risk for chronic users. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Biomimetic 3D-printed scaffolds for spinal cord injury repair.

Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation1. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (µCPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. µCPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6 s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of µCPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new 'neural relays' across sites of complete spinal cord injury in vivo in rodents1,2. We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine.

30-Day Emergency Department Visits After Primary Lumbar Fusion: Incidence, Causes, Risk Factors, and Costs.

Our objective was to describe the incidence, causes, risk factors, and costs associated with 30-day emergency department (ED) visits after primary lumbar fusion. A national insurance database was retrospectively analyzed to study patients with primary lumbar fusions performed for degenerative pathology of the spine between 2007 and Q3-2015. Risk factors for ED visits, and ED to hospital transfer were studied using multiple-variable logistic regression analysis. Our cohort included 37,559 patients with a mean age of 66.0±10.0 years. A total of 4806 (12.8%) patients had 10,281 ED visits within 30 days after surgery. Of these, 945 (19.9%) had multiple (≥3) visits, and 1466 (30.5%) were admitted to the hospital for management. Common causes for presentation in the ED were cardiorespiratory complaints (49.4%, n=2377), and back and/or leg pain (47.7%, n=2294). Risk factors for all ED visits, multiple ED visits, and hospital admission from the ED have been identified. The overall ED cost burden was nearly two-thirds as much as hospital readmissions within 30 days ($6,994,260 vs. $10,880,999). There is a sizable subset of patients that present to the ED for acute care but do not require hospitalization. Causes and risk factors for presentation in patients with multiple ED visits are somewhat different than patients requiring hospital readmission.