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Definitive diagnoses for included cats (n = 96)

CD4+ T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4+ T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4+ T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5 mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4+ T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4+ T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4+ T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4+ T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4+ T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene.

Since maturational processes triggering increased attunement to native language features in early infancy are sensitive to dietary factors, infant-diet related differences in brain processing of native-language speech stimuli might indicate variations in the onset of this tuning process. We measured cortical responses (ERPs) to syllables in 4 and 5 month old infants fed breast milk, milk formula, or soy formula and found syllable discrimination (P350) and syntactic-related functions (P600) but not syllable perception (P170) varied by diet, but not gender or background measures. The results suggest breastfed and formula-fed infants differ in onset of this critical period in speech perception.

Background Interventions to prevent sudden unexpected infant death (SUID) typically include education to increase knowledge, thereby improving parenting practice. However, health decision-making is based on a complex interplay of knowledge, attitudes, and beliefs related to intent to initiate behaviors. Further, based on the Health Belief Model, self-efficacy and locus of control are also linked to behavior change. Objective: This study examined the link between pregnant teens’ report on several safe sleep constructs thought to influence parent’s safe sleep behaviors and prenatal knowledge of safe sleep practices. Design/methods We recruited pregnant teens (13–19 years old) into a trial of an educational intervention for safe sleep during second trimester in a US state with high sleep-related SUID rates. A self-administered survey was completed before intervention. The survey included safe sleep constructs: attitudes (3 items), beliefs (4), self-efficacy (3), intentions (4), knowledge (3), and a standardized measure of knowledge of infant development (KIDI). Results 115 subjects completed baseline surveys, including 27 white (20%), 103 black (76%), and 5 other (4%) teens with median age 18 y±2. In regression analyses, the KIDI predicted safe sleep knowledge (R2=0.05, F(1, 112)=6.24, p Conclusions The prenatal period presents an important opportunity for educational intervention, as women develop knowledge and form beliefs that may shape early parenting behavior. The link between key safe sleep-related constructs may inform interventions before the birth. Our results suggest that safe sleep knowledge is associated with both key beliefs and with knowledge of general infant development. Interventions that target these beliefs may be more successful.

Marijuana legalization has increased the demand for testing of Δ9-tetrahydrocannabinol (THC) and THC metabolites. The THC ToxBox® test kit (THC ToxBox®) is commercially available and supports high-throughput LC-MS/MS analytical methods designed to quantify low levels of THC and THC metabolites in blood. The purpose of this study is to determine if this new test kit meets the rigors of laboratory accreditation and produces equivalent results across six states- and locally-funded laboratories. Each laboratory followed internal method validation procedures established for their clinical (CLIA) or international (ISO17025) accreditation program. Test performance indicators included accuracy, precision, measurement of uncertainty, calibration models, reportable range, sensitivity, specificity, carryover, interference, ion suppression/enhancement and analyte stability. Analytes and interferents were resolved within the 6-min analytical runtime, and the 48-well plate pre-manufactured with calibrators, second source quality control material, and internal standards at precise concentrations allowed for simple and consistent sample preparation in less than one hour. Every laboratory successfully validated test kit procedures for forensic use. Differences in sensitivity were generally associated with the use of older equipment. Statistical analysis of results spanning reportable ranges show that laboratories with different instrument platforms produce equivalent results at levels sufficiently low enough to support per se limit testing of THC and THC metabolites (1-5 ng/mL). THC ToxBox® represents a viable option for state- and locally-funded laboratories charged with investigating impaired driving cases involving marijuana use.

Trichloroethylene (TCE) is a widespread environmental pollutant associated with immunotoxicity and autoimmune disease. Previous studies showed that mice exposed from gestation through early life demonstrated CD4(+) T cell alterations and autoimmune hepatitis. Determining the role of one environmental risk factor for any disease is complicated by the presence of other stressors. Based on its known effects, we hypothesized that developmental overnutrition in the form of a moderately high-fat diet (HFD) consisting of 40% kcal fat would exacerbate the immunotoxicity and autoimmune-promoting effects of low-level (

Purpose Non-invasive ventilation (NIV) can be used in the neonate, precluding the need for intubation. Non-invasive intermittent positive pressure ventilation (NIPPV) is commonly used in neonatal intensive care units A relatively newer mode of non-invasive ventilation known as neurally adjusted ventilatory assist (NAVA) has a unique mechanism of patient-ventilator interaction using the electrical activity of the diaphragm to initiate mechanical breaths. There is little research looking at NIV- NAVA versus …

Background The relative influence of prematurity vs. maternal social factors (socioeconomic status and education level) on academic performance has rarely been examined. Objective To examine the impact of prematurity and maternal social factors on academic performance from 3rd through 8th grade. Methods We conducted a retrospective cohort study of infants born in 1998 at the University of Arkansas for Medical Sciences. The study sample included 58 extremely low gestational age newborns (ELGANs, 23‒

SummaryObjective The results from a recent national survey about catastrophic complications following tracheostomy revealed that the majority of events involved a loss of airway. Most of the events due to airway loss involved potentially correctable deficits in caregiver education. Training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the knowledge and confidence level of pediatric health care providers at a large tertiary care children's hospital in routine and emergency tracheostomy care and evaluated the efficacy of a comprehensive simulation-based tracheostomy educational program. Methods The prospective observational study was comprised of 33 subjects including pediatric residents, internal medicine–pediatric residents, pediatric hospitalist faculty physicians, and advanced practice registered nurses who are involved in the care of patients with tracheostomies within a tertiary-care children's hospital. The subjects completed self-assessment questionnaires and objective multiple-choice tests before and after attending a comprehensive educational course that employed patient simulation. The outcome measurements included pre- and post-course questionnaires, pre- and post-course test scores, and observational data from the simulation sessions. Results Before the education and simulation, the subjects’ comfort and confidence levels on a five-point Likert scale in performing routine tracheostomy tube care, routine tracheostomy tube change, and an emergency tracheostomy tube change were as follows (median (Q1, Q3)): 1 (1, 2), 1 (1, 2), and 1 (1, 2), respectively (n = 28). The levels of comfort and confidence after completing the course improved significantly to 4 (4, 5), 4 (4, 5), 4 (4, 5), respectively (P

BACKGROUND: There is little evidence in the medical literature to guide empiric treatment of pediatric patients with long-term tracheostomies who present with signs and symptoms of a bacterial respiratory infection. The overall goal of this study was to describe the respiratory microbiology in this study population at our institution. METHODS: This study was a retrospective chart review of all subjects with tracheostomies currently receiving care at the Arkansas Center for Respiratory Technology Dependent Children. Descriptive statistics were used to describe the respiratory microbiology of the full study group. Several subgroup analyses were conducted, including description of microbiology according to time with tracheostomy, mean time to isolation of specific organisms after the tracheostomy tube was placed, association between Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus isolation and prescribed antibiotic courses, and description of microbiology according to level of chronic respiratory support. Available respiratory culture results up to July 2011 were collected for all eligible subjects. Descriptive statistics were used to describe subject characteristics, and chi-square analysis was used to analyze associations between categorical data. P < .05 was considered statistically significant. RESULTS: A total of 93 subjects met inclusion criteria for the study. The median (interquartile range) age at time of tracheotomy was 0.84 (0.36–3.25) y, and the median (interquartile range) time with tracheostomy was 4.29 (2.77–9.49) y. The most common organism isolated was P. aeruginosa (90.3%), with Gram-negative organisms predominating. However, 55.9% of the study population had a respiratory culture positive for methicillin-resistant S. aureus . The first organism isolated after tracheostomy placement was Methiciliin-sensitive S. aureus was isolated the soonest after tracheostomy placement. Specific organisms were not related to level of chronic respiratory support or likelihood of receiving antibiotics. CONCLUSIONS: This study provides an updated overview of the variety of potential pathogens isolated from respiratory cultures of pediatric subjects with long-term tracheostomies.

Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear. Here we investigated the association between the aggressive proliferation of FLS and α7nAChR expression and the effect of sinomenine. FLS was isolated from synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis factor(TNF)-α was used to induce the aggressive proliferation of FLS. MTT assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA) and protein levels of α7nAChR and early growth response gene-1 (Egr-1) were measured. The results showed that TNF-α induced FLS proliferation in vitro (P < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1 and α7nAChR (P < .05 or P < .01). U0126, the inhibitor of ERK1/2 inhibited α7nAChR expression and FLS proliferation significantly (P < .05 or P < .01). Specific short interference RNA(siRNA) of α7nAChR decreased α7nAChR expression and inhibited FLS proliferation as well. SIN inhibited the proliferation of FLS and decreased the phosphorylation of ERK1/2, and the expression of Egr-1 and α7nAChR induced by TNF-α (P < .05). In conclusion, the expression of α7nAChR involved in the aggressive proliferation of FLS induced by TNF-α and was regulated by ERK/Egr-1 signal pathway. SIN inhibited FLS proliferation and α7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN.

Exposure to industrial solvent and water pollutant trichloroethylene (TCE) can promote autoimmunity, and expand effector/memory (CD62L) CD4+ T cells. In order to better understand etiology reduced representation bisulfite sequencing was used to study how a 40-week exposure to TCE in drinking water altered methylation of ∼337 770 CpG sites across the entire genome of effector/memory CD4+ T cells from MRL+/+ mice. Regardless of TCE exposure, 62% of CpG sites in autosomal chromosomes were hypomethylated (0–15% methylation), and 25% were hypermethylated (85–100% methylation). In contrast, only 6% of the CpGs on the X chromosome were hypomethylated, and 51% had mid-range methylation levels. In terms of TCE impact, TCE altered (≥ 10%) the methylation of 233 CpG sites in effector/memory CD4+ T cells. Approximately 31.7% of these differentially methylated sites occurred in regions known to bind one or more Polycomb group (PcG) proteins, namely Ezh2, Suz12, Mtf2 or Jarid2. In comparison, only 23.3% of CpG sites not differentially methylated by TCE were found in PcG protein binding regions. Transcriptomics revealed that TCE altered the expression of ∼560 genes in the same effector/memory CD4+ T cells. At least 80% of the immune genes altered by TCE had binding sites for PcG proteins flanking their transcription start site, or were regulated by other transcription factors that were in turn ordered by PcG proteins at their own transcription start site. Thus, PcG proteins, and the differential methylation of their binding sites, may represent a new mechanism by which TCE could alter the function of effector/memory CD4+ T cells.

The study aim was to describe the feasibility of conducting a coaching training intervention on use of level of assistance strategies for Certified Nursing Assistants (CNAs) in nursing homes. CNAs received either traditional or coaching training. Feasibility of coaching training was evaluated by determining: acceptability, through use of a Post-Intervention Evaluation Form; fidelity, by adherence to protocol; recruitment and retention, by ease of obtaining the sample and retention rates; and ability to randomize within each home without contamination. CNAs' mean satisfaction score of the coach training was high (4.5 out of 5). Eighteen of 22 comments on the evaluation form were positive. At least six dyads were recruited within the 60-day benchmark in each home. CNA and resident retention rates were 89.47% and 85%, respectively. Eighty-nine percent of intervention group CNAs shared study information, demonstrating contamination. The coaching training intervention is feasible. Findings revealed areas to improve the intervention.

Surgical site infection [SSI] is a risk for any surgical procedure, including hypospadias repair. Prophylactic antibiotic therapy for patients having surgery is often effective in preventing SSIs, but with increasing rates of antibiotic resistance, this practice has been questioned. The objectives of this study are 1) to assess the incidence of SSIs in patients following stented, distal hypospadias repair and 2) to observe for any potential difference in the incidence of SSIs for patients with and without preoperative antibiotic utilization in this setting.We retrospectively reviewed consecutive patients treated with stented, distal hypospadias repair from 2011 to 2014 by three surgeons and compared two groups: patients who received preoperative antibiotics and patients who did not. Patients with a history of previous hypospadias repair were excluded from the study.Two hundred twenty-four subjects were identified. Group 1 (135) received preoperative antibiotic and Group 2 (89) did not receive preoperative antibiotics. There was no statistically significant difference in SSI prevalence with 0 patients in Group 1 and 1 patient in Group 2 having a SSI.Although prophylactic antibiotics prior to hypospadias repair are most often used by pediatric urologists, this study demonstrates further evidence that antibiotics prior to this procedure do not appear to lower the rate of SSI. This study is limited by its retrospective nature and disparate mean follow up in the two cohorts. Surgical site infection does not appear to be decreased by prophylactic antibiotic therapy before distal hypospadias repair.

Background Home characteristics and aeroallergen exposure in rural US children with asthma are poorly described. Objective To examine the relationship between cockroach and mouse allergen concentrations and home characteristics of children with asthma in the rural Arkansas Delta. Methods The home environments of rural children with asthma were examined using home environment questionnaire and home inspection. Bedroom and kitchen dust was analyzed for cockroach and mouse allergen concentrations. Results The median age of participants was 9 years, and 84% were African American. Most participants (78%) resided in single-family homes. Evidence of cockroaches was detected in 13% of homes and evidence of rodents was detected in 23% of homes. Detectable Bla g 1 was found in 58% of kitchens and 43% of bedrooms, Bla g 2 was detected in 37% of kitchens and 28% of bedrooms, and Mus m 1 was found in 81% of kitchens and 97% of bedrooms. Evidence of cockroaches in any room was associated with Bla g 1 concentrations of ≥2 U/g (odds ratio 21.71, 95% confidence interval 4.26–118.39) and Bla g 2 concentrations of ≥2 U/g (odds ratio 21.90 95% confidence interval 4.30–138.91). Multifamily vs single-family dwellings were more likely to have Bla g 2 concentrations of ≥2 U/g (odds ratio 3.52, 95% confidence interval 1.0–11.82). Home characteristics were not associated with Mus m 1. Conclusion Mouse and cockroach allergens were detected in most rural homes; however, concentrations were relatively low compared with those previously reported in inner-city homes. Few home characteristics predicted allergen concentrations. Further studies are needed to establish clinically relevant associations that might place rural children with asthma at risk for poor clinical outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT00590304 .

Poly(ethylene glycol)-grafted graphene (PEG-g-G) was prepared and used as the solid phase microextraction (SPME) fiber coating for the extraction of seven volatile aromatic compounds (VACs) from water samples followed by the determination with gas chromatography-flame ionization detection. The PEG-g-G coating was characterized by both the thermal gravimetric analysis and scanning electron microscopy. The results verified that the PEG was successfully grafted onto the surface of graphene and the coating had a highly porous structure. Several important experimental parameters that could influence the SPME efficiency were investigated and optimized. Under the optimized conditions, the limits of detection were in the range from 1.0 to 6.0 ng L −1 . The relative standard deviations for intraday and interday variations were in the range of 1.8–5.8% and 5.1–8.3%, and for fiber-to-fiber variations, were between 6.5 and 11.9%, respectively. The results indicated that the PEG-g-G fiber had the advantages of high extraction efficiency and good thermal stability and durability. It can be reused more than 200 times without a significant loss of extraction efficiency. The method was successfully applied to the analysis of seven VACs in tap, river and mineral water samples.

A novel analytical method was developed for the extraction and determination of five chloroacetanilide herbicides (alachlor, acetochlor, metolachlor, butachlor and pretilachlor) in water and green tea samples by graphene-based magnetic solid phase extraction and dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection (GC-FID). Some important experimental parameters that could influence the extraction efficiency were investigated. Under the optimum conditions, as high as 3399 to 4002 fold enrichment factors for the herbicides were achieved. A good linearity was obtained in the range of 0.1–50.0 μg L−1 for all the five herbicides with the correlation coefficients (r) varying from 0.9973 to 0.9993. The limits of detection ranged from 0.01 to 0.03μg L−1. The method was applied to the analysis of the chloroacetanilide herbicides in environmental water and green tea samples with a satisfactory result. The recoveries of the method for the analytes were in the range from 80.2% to 105.3%, and the relative standard deviations were between 3.8% and 5.8%.

A highly sensitive method for the determination of the chloroacetanilide herbicides alachlor, acetochlor, pretilachlor, butachlor, and metolachlor in environmental water samples was developed. It is based on solid-phase extraction using magnetic graphene nanocomposite (G-Fe3O4) as the adsorbent, followed by gas chromatography with electron capture detection. This novel adsorbent showed a great adsorptive ability toward the analytes. The main experimental parameters such as the amount of G-Fe3O4, extraction time, ionic strength, the pH of the sample solution, and desorption conditions were optimized. Under the optimum conditions, the enrichment factors of the method for the analytes were in the range from 649 to 1078. A good linear response was achieved in the range of 0.2–20.0 ng mL−1, with correlation coefficients (r) varying from 0.9964 to 0.9998. The limits of detection of the method ranged from 0.02 to 0.05 ng mL−1 and the relative standard deviations were below 4.5%. The method was successfully appli...

BACKGROUND: Respiratory therapist (RT)-driven protocols have been in use for over 30 years. Protocols have been reported to decrease unnecessary or harmful therapy, health-care costs, and hospital stay. This study represents the evaluation of an original respiratory care protocol in the pediatric ICU at Arkansas Children9s Hospital for β-agonist and airway clearance interventions where one did not exist. METHODS: This project was composed of 2 parts: a survey administered to RTs and licensed independent practitioners and a retrospective review of outcome data comparing a therapist-driven β-agonist/airway clearance protocol with physician-directed respiratory care ordering in a patient population admitted for acute respiratory failure. RESULTS: Acceptance of the protocol was evident in the survey responses because overall perceptions surrounding the implementation of the β-agonist/airway clearance protocol were positive, and responders perceived that the protocol implementation elevated the status and increased the value of respiratory therapists. For the comparison of physician-directed orders with therapist-driven protocols, there were no significant differences between pre- and post-intervention groups for mean age, sex, mean daily acuity, or mean weighted daily acuity (P = .33, .19, >.99, and .79, respectively). There were also no differences in pediatric index of mortality 2, pediatric index of mortality 2 rate of mortality, pediatric risk of mortality 3 probability of death, and pediatric risk of mortality 3 scores (P = .63, .56, .19, and .44, respectively) between the 2 groups. When comparing physician-directed orders to therapist-driven protocols, all outcome measures (length of stay, β-agonist therapies, airway clearance therapies, and ventilator days) showed statistically and clinically important reductions, adjusting for subject characteristics (P CONCLUSIONS: In this institution, implementation of a β-agonist/airway clearance protocol resulted in significant reductions of subject interventions and improved outcomes by decreasing length of stay and ventilator days as well as contributing information where clinical evidence is scant, specifically the pediatric ICU.

This exploratory study compared juveniles who sexually offend to nonoffending juveniles in their capacities to behaviorally and neurologically regulate, or reappraise, negative emotions. Participants were 39 juvenile males, including 10 healthy, nonoffending control subjects and 29 juveniles who sexually offend, comprising 12 juveniles who sexually offend with history of child sexual abuse. Participants completed a clinical assessment and a reappraisal task during functional magnetic resonance imaging. Difficulties in Emotional Regulation Scale results showed significantly less difficulties in emotion regulation among controls compared to juveniles who sexually offend, but when self-rating reappraisal abilities during the functional magnetic resonance imaging, all groups obtained comparable results. The imaging results showed no significant differences in fronto-temporal regions between controls and juveniles who sexually offend. Differences were found in other regions indicated in cognitive control, working memory, and emotional processing between controls and juveniles who sexually offend as well as between juveniles who sexually offend and those without history of child sexual abuse. Findings suggest that juveniles who sexually offend are capable of emotion regulation.

In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. Trial registration ClinicalTrials.gov : NCT01913340 .

BACKGROUND: Volutrauma has been established as the key factor in ventilator-induced lung injury and can only be avoided if tidal volume (VT) is accurately displayed and delivered. The purpose of this study was to investigate the accuracy of displayed exhaled VT in a ventilator commonly used in small infants with or without a proximal flow sensor and using 3 methods to achieve a target VT in both a healthy and lung-injured neonatal pig model. METHODS: This was a prospective animal study utilizing 8 male pigs, approximately 2.0 kg (range 1.8–2.2 kg). Intubated, sedated, neonatal pigs were studied with both healthy and injured lungs using the Servo-i ventilator. In pressure-regulated volume control, both with and without a proximal flow sensor, we used 3 methods to set VT: (1) circuit compliance compensation (CCC) on, set VT 6–8 mL/kg; (2) CCC off, calculated VT using the manufacturer9s circuit compliance factor; and (3) CCC off, set VT 10–12 mL/kg to approximate a target VT of 6–8 mL/kg. Ventilator-displayed exhaled VT measurements were compared with exhaled VT measured at the airway opening by a calibrated pneumotachograph. Bland-Altman plots were constructed to show the level of agreement between the two. RESULTS: CCC improved accuracy and precision of displayed exhaled VT when the sensor was not used, more markedly in the lung-injured model. Without CCC, the sensor improved accuracy and precision of displayed exhaled VT, again more markedly in the lung-injured model. CONCLUSIONS: When the Servo-i ventilator is used in neonates, CCC or the in-line sensor should be employed due to the large positive bias and imprecision seen with CCC off and no sensor in-line.

BACKGROUND Patient-ventilator asynchrony can result in increased work of breathing (WOB) and need for increased sedation, as well as respiratory muscle fatigue and prolonged mechanical ventilation. Different ventilator modes may result in varying degrees of asynchrony and WOB. OBJECTIVE The objectives of this study were to assess the incidence of asynchrony and the effect of asynchrony on WOB in three modes of ventilation: pressure regulated volume control (PRVC), synchronized intermittent mandatory ventilation/volume control plus pressure support (SIMV/VC plus PS), and SIMV/PRVC plus PS. METHODS Ten piglets (2.1 ± 0.3 kg) were studied, each in the healthy and surfactant-depleted, lung-injured state. Piglets were sedated, intubated, and ventilated with the three modes of ventilation randomly applied. Piglets then underwent surfactant washout, after which the lungs were re-recruited, and the modes of ventilation were repeated. Airway flow and pressure waveforms were acquired via pneumotachograph. Waveforms were analyzed for patient-ventilator asynchrony and pressure time product (PTP) as an estimate of patient WOB. RESULTS SIMV/VC plus PS had the highest incidence of asynchrony. The incidence of asynchrony was less in the injured lung. PTP (cm H2O*S) was increased for SIMV/VC plus PS (healthy 0.10 ± 0.12; injured 0.15 ± 0.13) compared to PRVC (healthy 0.05 ± 0.05; injured 0.06 ± 0.03), (P

A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation.Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/mNo patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P0.05) in AUCPharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered.

To evaluate the influence of early feeding on initial glucose concentrations in healthy term newborns who were not at risk for hypoglycemia.This retrospective observational study was conducted at the University of Arkansas for Medical Sciences where universal early glucose screening was standard of care for newborn infants. Plasma glucose concentrations were compared in term infants born in 2008 who were not at risk for neonatal hypoglycemia and who were fed before (early feeders) and after (late feeders) their initial glucose screens. Multiple linear regression models were built to determine whether glucose concentrations differed significantly between early vs late feeders.In the 315 early and 572 late feeders, the mean (SD) age of first feeding was 0.9 (0.6) and 3.8 (2.0) hours, respectively. The age at initial glucose specimen collection was 2.2 (1.1) and 1.8 (0.8) hours, respectively. The initial glucose concentration was not higher in early vs late feeders (51.8 ± 11.9 vs 55.5 ± 13.3 mg/dL; P .001). In linear regression analyses of all infants, the mean initial glucose concentration was 3.61 (95% CI 1.75-5.48) mg/dL lower in early vs late feeders.Early feeding in otherwise healthy term newborns did not increase initial glucose concentrations compared with newborns who fed later (ie, fasted). Before direct evidence is available, these observations may be instructive for managing early asymptomatic hypoglycemia in at-risk newborns.

Aim: Autoimmune disease and CD4+ T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4+ T cells as a possible mechanism of immunotoxicity. Materials & methods: Naive and effector/memory CD4+ T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. Results: A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4+ T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. Conclusion: TCE increased epigenetic drift of specific CpG sites in CD4+ T cells.

A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts.We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables.AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases.The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

To effectively address the needs of youth who perpetrate sexual violence and reduce rates of recidivism, a better understanding of the mechanisms of juvenile sexual offending is needed. Current literature identifies various factors that are believed to put youth at risk for sexual offending, two of which are empathy deficits and childhood sexual abuse (CSA). The extent to which empathy deficits contribute to juvenile sexual offending, however, is often debated, though studies have not yet explored a neurobehavioral model of this mechanism. This pilot study used functional magnetic resonance imaging (fMRI) to explore the neural correlates of empathy in juveniles who sexually offend (JSOs), and the possible role of CSA. A total of 38 males (ages 12-20) were enrolled, including 11 healthy control subjects and 27 JSOs, of which, 11 had a history of CSA. Participants underwent clinical assessment and completed an empathy task during fMRI. Using both whole-brain and region-of-interest analysis, results of the fMRI data showed no statistical differences in engagement of brain regions associated with empathy between controls and all JSOs. There were also no significant differences between JSOs with and without a history of CSA. These null findings pose implications for guiding future research studies with larger samples and more statistical power, and may support the need to further explore empathy-related explanatory models and interventions for JSOs. Neuroimaging may demonstrate to be a useful tool to identify individualized risk factors and aid in tailoring interventions for this population.

β phase polyoctylfluorene thin films were obtained by exposure to toluene vapor for various annealing times or dipping into a THF/methanol mixture. The photoluminescence and electroluminescence of PFO thin films decrease with increasing annealing time. Grazing incident X-ray diffraction of the thin films indicates that more and larger β phase crystallites will be generated in thin film exposed for longer time, which will lead to more defects that reduce photoluminescence and electroluminescence. By analyzing the mechanism of formation of β phase, we assume that the defects mainly come from the formation of out-of-plane crystalline structure. The assumption is confirmed by higher photoluminescence of β phase polyoctylfluorene thin film achieved by dipping into a THF/methanol mixture that has less out-of-plane crystalline structure.

The corrosion of coal mine equipment immersed in coal slurry is addressed. The corrosion of low carbon steel samples immersed in coal slurries of different concentrations (80, 130, and 180 g/L) prepared from coals of different rank (long-flame coal, meager lean coal, and anthracite) and different granularity (0.25–0.5 mm, 0.074–0.25 mm, and less than 0.074 mm particle size) was studied by the electrochemical method of polarization curve measurement, controlled potential sweeping, and continuous scanning. The results show that the corrosion rate in an anthracite slurry, where the coal has high coalification, is far greater than corrosion in a long-flame or a meager lean coal slurry. Furthermore the corrosion current, polarization current, and corrosion rate of low carbon steel become larger, and the polarizability becomes smaller, as the coal particle size decreases. The same trend is seen as the concentration of the coal slurry increases.

The usage of prophylactic oral antibiotics following distal hypospadias repair with stenting has been recently challenged. This study evaluated the incidence of symptomatic urinary tract infections (UTIs) following stented, distal hypospadias repair and the impact of prophylactic antibiotic therapy. Subjects 0 to 5 years of age with distal hypospadias were randomized to either Group 1 (antibiotics) or Group 2 (no prophylactic therapy). Urinalysis/urine culture was obtained intraoperatively with no preoperative antibiotics given. Phone interviews at 1 month and 3 months after surgery were done. Forty-eight patients were successfully randomized to either Group 1 (24) or Group 2 (24). The incidence of symptomatic UTI in this pilot study is low, and prophylactic antibiotic therapy does not appear to lower the incidence of symptomatic UTI. A larger, randomized, multicenter trial is needed to determine whether antibiotic prophylaxis reduces the risk of symptomatic UTIs following stented, distal hypospadias repair.

Background Direct observation of health care worker (HCW) hand hygiene (HH) remains the gold standard, but implementation is challenging. Our objective was to develop an accurate HH observation program using multiple HCW volunteers. Methods HH compliance was defined as correct HH performed before and after contact with a patient or a patient's environment. HCW volunteers from each unit at our children's hospital were trained by infection preventionists to covertly collect HH observations during routine care using an electronic tool. Questionnaires sent to observers in February and December 2014 recorded demographic characteristics, observation time, and scenarios assessing accuracy. HCWs were surveyed regarding their awareness that their HH behavior was being recorded. Results There were 146 HH observers. The majority of observers reported making 1-2 observations per shift (65%) and taking ≤10 minutes recording an observation (85%). Between January 2012 and December 2014 there were 22,484 HH observations (average, 622 per month), including nurses (46%), physicians (21%), and other HCWs (33%). Observers correctly recorded HH behavior more than 90% of the time in 5 of the 6 scenarios. Most HCWs (86%) were unaware they were being observed. Conclusion A direct observation program staffed by multiple HCW volunteers can inexpensively and accurately collect HCW HH data.

Background A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Methods Twenty-two children (6–17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25–115 mg/m2) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography–tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. Results No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P

Background: Congenital heart disease (CHD) occurs in about 80% of patients with Trisomy 13 (T13), but surgical repair has not been offered to these patients in most centers because of low median survival. Data on congenital heart surgery (CHS) for T13 are lacking. Methods: Nationally distributed

Background Arterial stiffness assessed by carotid-femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of obesity affect arterial stiffness. Methods We conducted a population-based cross-sectional survey in 8,042 South Indians above the age of 20 years. Following completion of a detailed medical history questionnaire, all participants underwent haemodynamic screening including brachial and central blood pressure, and PWV measurements using a high-fidelity applanation tonometry. The study included anthropometric measurements and fasting blood for total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and blood glucose (BG) levels. After the exclusion of people with previous history of diabetes, hypertension and dyslipidemia on drug therapy, 5,841 subjects (mean age 41.6 years; 58% women) constituted the study sample Results In an univariate analysis, PWV correlated positively with age, mean blood pressure (MAP), heart rate (HR), body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), body fat percent (BF%), TC, TG, LDL and BG levels (P Conclusion: In a large a population-based cross-sectional survey the study demonstrates a positive, independent association between obesity parameters and increased arterial stiffness.

In this paper, a sensitive analytical method for four fungicides (procymidone, folpet, vinclozolin and ditalimfos) in environmental water and juice samples was developed by using magnetic solid-phase extraction (MSPE) with magnetic graphene nanocomposite (G-Fe3O4) as the adsorbent, followed by determination with gas chromatography and electron capture detection. Parameters such as the amount of G-Fe3O4, extraction time, ionic strength and pH of the sample solution, desorption solvent and desorption time were optimized. Under the optimum conditions, the enrichment factors of the method for the analytes were in the range from 1495 to 1849. The limits of detection for the fungicides ranged from 1.0 to 7.0 ng L(-1). The recoveries of the method for the analytes were in the range from 79.2 to 102.4%. The developed G-Fe3O4-MSPE method was simple and efficient for the extraction and determination of the four fungicides in water and grape juice samples.

We have previously reported the design of a new PCR primer pair that allows amplification of a broad range of eubacterial 16S rDNA sequences from ectomycorrhizae (ECM) without co-amplification of plastid or mitochondrial sequences. Here, we report using a similar primer combination to generate three small 16S rDNA libraries from tuberculate ECM of Rhizopogon spp., two from R. vinicolor ECM (libraries Rvi18 and Rvi24) and one from R. vesiculosus ECM (library Rve13). At the class level, libraries were dominated by sequences from the Alphaproteobacteria, Gammaproteobacteria, and Acidobacteria, with some Sphingobacteria, Actinobacteria, Planctomycetacia, and Verrucomicrobiae present as well. Based on the parsimony test implemented in TreeClimber, libraries Rvi18 and Rvi24 were significantly different from Rve13 at the alpha = 0.05 level, while they were only borderline significantly different from each other (p = 0.07). Differences between Rvi and Rve libraries were primarily due to differences in the number of Alphaproteobacteria sequences and specifically sequences from the Rhizobiales, which were more common in the Rve13 library. It is currently unknown what drives these differences between eubacterial communities. Amplification success for eubacterial 16S rDNA sequences was generally low in this study indicating low abundance of bacteria on tuberculate ECM. Attempts to amplify nitrogenase reductase (nifH) sequences were unsuccessful.

Importance Prolonged neonatal hypoglycemia is associated with poor long-term neurocognitive function. However, little is known about an association between early transient newborn hypoglycemia and academic achievement. Objective To determine if early (within the first 3 hours of life) transient hypoglycemia (a single initial low glucose concentration, followed by a second value above a cutoff) is associated with subsequent poor academic performance. Design, Setting, and Participants A retrospective population-based cohort study of all infants born between January 1, 1998, and December 31, 1998, at the University of Arkansas for Medical Sciences who had at least 1 recorded glucose concentration (a universal newborn glucose screening policy was in effect) was conducted. Medical record data from newborns with normoglycemia or transient hypoglycemia were matched with their student achievement test scores in 2008 from the Arkansas Department of Education and anonymized. Logistic regression models were developed to evaluate the association between transient hypoglycemia and school-age achievement test proficiency based on perinatal factors. Common hypoglycemia cutoffs of a glucose level less than 35 mg/dL (primary) and less than 40 and 45 mg/dL (secondary) were investigated. All 1943 normoglycemic and transiently hypoglycemic infants (23-42 weeks’ gestation) were eligible for inclusion in the study. Infants with prolonged hypoglycemia, congenital anomalies, or chromosomal abnormalities were excluded from the study. Exposure Hypoglycemia as a newborn. Main Outcomes and Measures The primary outcome was proficiency on fourth-grade literacy and mathematics achievement tests at age 10 years. We hypothesized a priori that newborns with early transient hypoglycemia would be less proficient on fourth-grade achievement tests compared with normoglycemic newborns. Results Perinatal data were matched with fourth-grade achievement test scores in 1395 newborn-student pairs (71.8%). Transient hypoglycemia (glucose level Conclusions and Relevance Early transient newborn hypoglycemia was associated with lower achievement test scores at age 10 years. Given that our findings are serious and contrary to expert opinion, the results need to be validated in other populations before universal newborn glucose screening should be adopted.