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BACKGROUND: As part of efforts to decrease length of hospital stay, a protocol for weaning noninvasive respiratory support was implemented using quality improvement methodology. The objective of this study was to determine whether protocol implementation decreased the time to wean to no respiratory support by 24 h (30% reduction) over 3 months in preterm infants 30–34 weeks gestational age. METHODS: A quality improvement project was conducted with the following outcome measures: primary outcome measured was hours to wean; secondary outcomes included duration of respiratory support, length of stay, and postmenstrual age at feeding milestones; and balance measures were duration of oxygen exposure and growth velocity. RESULTS: Data from 89 subjects were included. Following implementation, decreases were seen in time to wean (40% reduction, P < .001), length of stay (25% reduction, P = .02), and growth velocity (21% reduction, P = .02). CONCLUSIONS: Implementing a weaning protocol decreases duration of support and length of stay in infants 30–34 weeks gestational age. Weaning respiratory support more quickly may decrease growth velocity.

Objective:Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality.Methods:A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed.Results:The incidence of acute kidney injury is 13.4–20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047).Discussion:The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.

Medication refusal in children is largely driven by aversive taste profiles, which in turn influence adherence and therapeutic outcomes. However, there are no standardized methods for evaluating taste in young children. This study compares facial recognition technology with three hedonic visual scales in this population. Children, 3–7 years of age, were enrolled with informed parental permission into an institutional review board-approved, double-blind, randomized investigation. Each child received three test articles: prednisone (bitter), simple syrup (sweet), and filtered water (neutral), with an appropriate washout. Facial recognition software (Noldus FaceReader 7) recorded facial expression and intensity for 30–60 s after administration. Participants subsequently rated taste using three hedonic scales (5-point Sjovall and 5- and 3-point TASTY) and responded to simple questions on their perception of the test article. Repeated measures analysis of variance and multiple regression analysis were used to explore associations between palatability measures. Twelve children (seven males: ten white and two black) completed the study without adverse effects. There were no significant differences in participant characteristics by randomization sequence. The three hedonic scales tracked similarly for each test substance, with correlations between the 5-point scales (r = 0.899) comparable to those between the 3- and 5-point scales (r = 0.860–0.903). Hedonic scales appeared more reliable in assessing taste response than facial recognition, which did not effectively discriminate positive and negative responses. Our experience suggests that the TASTY scales appear to offer the greatest promise for assessing palatability in future clinical use.

Lung cancer is the leading cause of cancer deaths worldwide, with a high morbidity and less than 20% survival rate. Therefore, new treatment strategies and drugs are needed to reduce the mortality of patients with lung cancer. α7 nicotinic acetylcholine receptor (α7 nAChR), as a receptor of nicotine and its metabolites, is a potential target for lung cancer treatment. Our previous studies revealed that sinomenine plays anti-inflammation roles via α7 nAChR and down-regulates the expression of this receptor, thus increasing the inflammatory response. Hence, sinomenine is possibly a natural ligand of this receptor. In the present study, the effects of sinomenine on lung cancer A549 cells and tumor-bearing mice were determined to investigate whether this alkaloid has an inhibitory effect on lung cancer via α7 nAChR. CCK-8 assay, wound-healing test, and flow cytometry were performed for cell proliferation, cell migration, and apoptosis analysis in vitro, respectively. Xenograft mice were used to evaluate the effects of sinomenine in vivo. Results showed that sinomenine decreased cell proliferation and migration abilities but increased the percentage of apoptotic cells. Tumor volume in tumor-bearing mice was significantly reduced after sinomenine treatment compared with that in the vehicle group mice (p < 0.05). Furthermore, the effects of sinomenine were abolished by the α7 nAChR antagonist mecamylamine and the allosteric modulator PNU-120596, but no change occurred when the mice were pretreated with the muscarinic acetylcholine receptor antagonist atropine. Meanwhile, sinomenine suppressed α7 nAChR expression in vitro and in vivo, as well as the related signaling molecules pERK1/2 and ERK1/2 and the transcription factors TTF-1 and SP-1. By contrast, sinomenine up-regulated the expression of another transcription factor, Egr-1. These effects were restricted by mecamylamine and PNU but not by atropine. Results suggested that sinomenine can inhibit lung cancer via α7 nAChR in a negative feedback mode.

Objectives The aim of this study was to evaluate the intra- and inter-rater reliability of epaxial muscle cross-sectional area measurement on feline CT images and to determine the relationship between normalized epaxial muscle area (EMA) and subjective muscle condition score (MCS). Methods Feline transverse CT images including the junction of the 13th thoracic vertebrae/13th rib head were retrospectively reviewed. Right and left epaxial muscle circumference and vertebral body height were measured and an average normalized EMA (ratio of epaxial area:vertebral height) was calculated for each image. Measurements were performed by three individuals blinded to the clinical data and were repeated 1 month later. Intra- and inter-rater reliability of EMA was assessed with concordance correlation coefficient (CCC), and Bland–Altman analysis was performed to assess bias and limits of agreement (LoA) between and within observers at different time points. In cats for which MCS data were available, EMA was compared between differing MCSs via the Kruskal–Wallis test, with Bonferroni-corrected Wilcoxon rank-sum post-hoc analysis. Results In total, 101 CT scans met the inclusion criteria for reliability analysis, 29 of which had muscle condition information available for analysis. Intra-rater EMA CCC ranged from 0.84 to 0.99 with minimal bias (range –0.16 to 0.08) and narrow LoA. Inter-rater EMA CCC ranged from 0.87 to 0.94, bias was larger (range –0.46 to 0.66) and LoA were wider when assessed between observers. Median EMA was significantly lower in cats with severe muscle atrophy (2.76, range 1.28–3.96) than in all other MCS groups ( P Conclusions and relevance Measurement of EMA on CT showed strong intra-rater reliability, and median EMA measurements were significantly lower in cats with severe muscle wasting, as assessed on physical examination. Further studies correlating EMA to lean muscle mass in cats are needed to determine whether this method may be useful to quantify muscle mass in patients undergoing a CT scan.

Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a relationship between α7nAChR and RA. This study investigated the relationship between α7nAChR and RA development and the effects of SIN on α7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund’s adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters—paw volume, arthritic index (AI), serum TNF-α concentration, and erythrocyte sedimentation rate (ESR)—were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. α7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between α7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF-α concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased α7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on α7nAChR expression. Moreover, there was a positive relationship between α7nAChR expression and paw swelling, AI, and TNF-α concentration. Splenic lymphocyte activation was accompanied by increased α7nAChR expression, while SIN treatment inhibited cell activation and downregulated α7nAChR expression. α7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on α7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.

Nasal intermittent positive pressure ventilation (NIPPV) is a widely used mode of support in neonates, during which ventilator inflations may or may not coincide with spontaneous breathing. We tested the hypothesis that inflations delivered with NIPPV via RAM® cannula and not accompanied by patient effort produce minimal tidal volume as measured by respiratory inductance plethysmography. Fourteen subjects were monitored while receiving NIPPV. We compared tidal volumes during ventilator-supported breaths, unsupported breaths, and ventilator inflations not accompanied by patient effort (defined using electrical activity of the diaphragm). Mean tidal volumes in arbitrary units were 0.30 ± 0.22 in NIPPV inflations associated with patient effort and 0.27 ± 0.15 in spontaneous breaths without ventilator assistance (p = 0.82). Tidal volumes during ventilator-only inflations were 0.06 ± 0.04 (p

The Coronavirus disease 2019 (COVID‐19) pandemic profoundly impacted health care utilization. We evaluated asthma‐related emergency department (ED) and inpatient health care utilization by a county‐specific Medicaid population, ages 2–18, during the COVID‐19 pandemic and compared it to utilization from a 3‐year average including 2017–2019. All‐cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017–2019 3‐year average, cumulative asthma‐related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma‐related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the “Stay‐at‐home” order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health‐associated benefits.

Early diagnosis via newborn screening is crucial to improve clinical outcomes in patients with cystic fibrosis (CF). In resource-limited areas where newborn screening is unavailable and CF-related morbidity is high, clinical tools such as palmar aquagenic wrinkling (AW) have been considered. We report the utility of AW for possible early identification of CF in children2 years old.This pilot case-control study included 55 total children, 20 with confirmed CF, 10 CF carriers, and 25 healthy controls. The time to wrinkling (TTW) after hand immersion in water was recorded, and relationships between TTW, demographic and clinical variables, and validated diagnostic tests were analyzed.Wrinkling was observed in children2 years of age, and median TTW was significantly lower among those with CF (3 min) compared to carriers or healthy controls (12 and 14 min, respectively). Higher immunoreactive trypsinogen and sweat chloride levels were associated with lower TTW (p 0.001). In this predominantly Caucasian cohort, children with F508del had the lowest TTW. Six minutes of hand immersion offered a sensitivity of 85% and a specificity of 91%, suggesting a practical and effective test duration for this age. There was no evidence that nutritional status affected TTW.Our data confirm the role of AW in CF, validate test utility among young children, and analyze relationships between TTW, immunoreactive trypsinogen, sweat chloride levels, and CF-causing mutations. Despite test limitations, in children with suspected CF from non-screened populations, utility of AW in enabling early referral and diagnosis needs further exploration.

Background Measurements of gastric emptying (GE) by scintigraphy in the pediatric population are based on adult standards. Due to radiation exposure, scintigraphy cannot be performed on healthy children to establish norms of GE in the pediatric population. Stable isotope breath tests (GEBTs) pose no such health risk to children. This study sought to determine the feasibility of a GEBT in children and to investigate whether GE may differ by age, gender, or body mass index (BMI). Methods Fifty healthy children 6 to 18 years underwent a 13 C-Spirulina platensis GEBT. Breath samples were obtained at baseline, every 15 min for 1 h, and at 30-min intervals for 3 h thereafter. Seventeen similarly aged patients with dyspeptic symptoms concurrently underwent scintigraphy and the GEBT. Key results Forty-six healthy subjects were included in the final analysis. Females had an overall slower rate of GE than did males. At nearly all timepoints, children with a BMI >85th percentile had slower GE than normally weighted children. The GE rate of children aged 6-9 reached a maximum later than did the rate of older children. Thirteen patients undergoing scintigraphy were included in the comparative analysis. The agreement between scintigraphic and GEBT half-times as measured by the concordance correlation coefficient was 0.383 (95% CI: 0.02-0.65). Conclusions and inferences GEBT was easily accomplished in healthy children. Differences of GE rates by age, gender, and BMI support the need for establishing pediatric standards of GE. One way to establish such standards may be through the use of a GEBT.

Background: We report the design, protocol and statistical analysis plan for the Arkansas Active Kids (AAK) Study. The study investigates the complex relationships between factors that contribute to metabolic health and obesity status in prepubertal school-age children in the state of Arkansas. Aim: We aim to identify modifiable behavioral and environmental factors and phenotypes related to metabolic health that are associated with obesity status that, if addressed effectively, can aid in designing effective intervention strategies to improve fitness and reduce obesity in children. Methods: We analyzed dietary and physical activity data from two national surveys (National Survey of Children’s Health and Youth Risk Behavior Surveillance System). We then conducted detailed surveys to collect dietary, physical activity, socio-demographic, and environmental data from a sample of 226 prepubertal Arkansas children. In the same sample of prepubertal children, we also collected extensive physiologic data to further study associations between physical activity and metabolic health. Results: All study visits included detailed measures of vital signs, energy expenditure, components of physical fitness, body composition and the collection of biological samples for determination of metabolic analytes. Conclusion: The observational, environmental and physiological results will be used to craft multivariate statistical models to identify which variables define ‘phenotype signatures’ that associate with fitness level and obesity status.

Psychological stress is a common etiology among patients with lung cancer and serves as a potential indication of poor prognosis and advanced cancer clinical stage. Evidence indicates that depression is positively correlated with the evolvement of lung carcinoma. Nevertheless, the mechanisms underlying the effects of mental disorder on lung cancer have not been considerably and systemically explored. We hypothesized that mental disorder may affect the adjustment of the tumor microenvironment and immune cells. We used the chronic unpredictable mild stress (CUMS) procedure to induce depressed mice models and established tumor-bearing models of C57BL/6 J mice. Results revealed that the worsening of lung cancer was notably hastened in the CUMS + tumor group. Notably, the expression of PD-L1 in tumor issues increased in the tumor microenvironment, accompanied with a decline in the levels of CD8. On the basis of the date of tumor migration, our results indicated that MMPs and VEGF significantly increased after CUMS + tumor treatment. Thus, we demonstrated that modulation of the tumor microenvironment is pivotal for depression-promoted lung cancer migration.

Background: There is a pressing need for effective and non-invasive biomarkers to track intrahepatic triglyceride (IHTG) in children at-risk for non-alcoholic fatty liver disease (NAFLD), as standard-of-care reference tools, liver biopsy and magnetic resonance imaging (MRI), are impractical to monitor the course disease. Objective: We aimed to examine the association between serum fibroblast growth factor (FGF)-21 to adiponectin ratio (FAR) and IHTG as assessed by MRI in children with obesity. Methods: Serum FGF21 and adiponectin levels and IHTG were measured at two time points (baseline, 6 months) in obese children enrolled in a clinical weight loss program. The association between percent change in FAR and IHTG at final visit was examined using a multiple linear regression model. Results: At baseline, FAR was higher in the subjects with NAFLD (n = 23, 35.8 ± 41.9 pg/ng) than without NAFLD (n = 35, 19.8 ± 13.7 pg/ng; p = 0.042). Forty-eight subjects completed both visits and were divided into IHTG loss (≥1% reduction than baseline), no change (within ±1% change), and gain (≥1% increase than baseline) groups. At 6 months, the percent change in FAR was different among the three groups (p = 0.005). Multiple linear regression showed a positive relationship between percent change in FAR and the final liver fat percent in sex and pubertal stage-similar subjects with NAFLD at baseline (slope coefficient 6.18, 95% CI 1.90–10.47, P = 0.007), but not in those without NAFLD. Conclusions: Higher value in percent increase in FAR is positively associated with higher level of IHTG percent value at 6 months in children with baseline NAFLD. FAR could be a potential biomarker to monitor the changes in IHTG in children with NAFLD.

β-Amyloid (Aβ) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3β (GSK-3β) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3β is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavone, was previously shown to be a highly selective inhibitor of GSK-3β, while exerting neuroprotective effects in neuronal models of AD. In the present study, we evaluated the in vivo effects of isoorientin on GSK-3β, tau phosphorylation, Aβ deposition, neuroinflammatory response, long-term potentiation, and spatial memory in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice using biochemical, electrophysiological, and behavioral tests. Chronic oral administration of isoorientin to APP/PS1 mice at 8 months of age attenuated multiple AD pathogenic hallmarks in the brains, including GSK-3β overactivation, tau hyperphosphorylation, Aβ deposition, and neuroinflammation. For neuroinflammation, isoorientin treatment reduced the number of activated microglia associated with Aβ-positive plaques, and in parallel reduced the levels of pro-inflammatory factors in the brains of APP/PS1 mice. Strikingly, isoorientin reversed deficits in synaptic long-term potentiation and spatial memory relevant to cognitive functions. Together, the findings suggest that isoorientin is a brain neuroprotector and may be a promising drug lead for treatment of AD and related neurodegenerative disorders.

Background Adverse stress in early life negatively influences psychiatric health by increasing the risk of developing depression and suicide in adulthood. Clinical antidepressants, such as fluoxetine, exhibit unsatisfactory results due to their low efficacy or intolerable side effects. SiNiSan (SNS), a traditional Chinese herbal formula, has been proven to have affirmatory antidepressive effects. However, the underlying mechanism remains poorly understood. Therefore, this study aimed to explore the impact and molecular mechanism of SNS treatment in rats exposed to neonatal maternal separation (MS)-combined young–adult chronic unpredictable mild stress (CUMS). Method Seventy-two neonatal male Sprague–Dawley rats were randomly divided into six groups of 12 rats each: control + ddH2O, model + ddH2O, positive (fluoxetine: 5 mg/kg), SNS-low dose (2.5 g/kg), SNS-medium dose (5 g/kg), and SNS-high dose (10 g/kg). Behavioral tests included sucrose preference test, open-field test, and forced swimming test. Calcium sensitive receptor (CaSR), protein kinase C (PKC), ERK1/2, and synapse-associated proteins (PSD-95, GAP-43, and synaptophysin [Syn]) in the hippocampus (HIP) and prefrontal cortex (PFC) were assayed using Western blot. CaSR and Syn protein expression was measured by immunohistochemistry. Results MS-combined CUMS rats exhibited depression-like behavior. SNS exerted antidepressant effects on stress-induced depression-like behavior. The levels of CaSR, PKC, and p-ERK1/2 in the HIP and PFC decreased in stressed rats. SNS treatment significantly upregulated the expression of CaSR, PKC, and p-ERK1/2 in the HIP and PFC of adult stressed rats. Conclusion MS-combined CUMS could develop depression-like behavior in adult. SNS exhibited antidepressive effects accompanied by improving synaptic plasticity by activation of the CaSR-PKC-ERK signaling pathway.

More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC–MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.

BACKGROUND: We tested whether work of breathing in premature newborns estimated by phase angle (θ) by using respiratory inductance plethysmography is decreased during neurally-adjusted ventilatory assist (NAVA) noninvasive ventilation (NIV) versus NIV alone. METHODS: NAVA NIV and NIV were applied in random order while using respiratory inductance plethysmography to measure the phase angle. RESULTS: Patient-ventilator asynchrony was decreased during NAVA NIV; however, the phase angle was not different between the modes. A large number of repeated assists with switches to backup were found when using NAVA NIV. Results of the analysis indicated these were due to the apnea alarm limit set during NAVA NIV. CONCLUSIONS: The improvement in patient-ventilator synchrony supports the hypothesis that work of breathing may be decreased with NAVA NIV; however, we were unable to demonstrate this with our study design. Short apnea time settings with NAVA NIV led to a large number of switches to backup and repeated assists during the same neural effort. (ClinicalTrials.gov registration NCT02788110.)

The arterial switch operation (ASO) in complete transposition of the great arteries (TGA) has increased long-term survival. Annual follow-up echocardiograms are recommended, but evidence-based guidelines do not exist. We sought to assess how often a patient with TGA after ASO who had no symptoms or change in physical exam underwent an intervention based solely on echocardiographic changes. We retrospectively reviewed all records from patients with TGA and a history of ASO followed at our institution between November 1983 and January 2015. Changes in echocardiograms resulting in hospital admission, significant medication change, interventional catheterization, or surgical procedure were identified through the surgical and cardiac catheterization laboratory databases and patient charts. These changes were referred to as an actionable change (AC). Interventions were defined as being driven by either clinical (change in physical exam, patient and/or parental concerns) or echocardiographic findings. A total of 1,792 echocardiograms from 149 patients were reviewed. Median number of echocardiograms per patient was 12 (1 to 34). Of the 1,792 echocardiograms, 20 (1.12%) were associated with AC. The most common intervention for an AC was cardiac catheterization (13 of 20, 65%). Most AC (15 of 20, 75%) occurred in the first decade after ASO. AC occurred in 83% (5 of 6) of those with a history of both ASO and arch repair. Annual echocardiograms in patients with TGA after ASO are rarely useful and are unnecessary. In conclusion, decreasing surveillance of asymptomatic patients to biennial follow-up echocardiograms in asymptomatic patients without physical examination changes is safe and would decrease medical expenses.

Objective This study examined the prevalence of compassion fatigue and life stress of pediatric nurses. Background Distressing patient situations over time may affect nurses' professional quality of life and result in compassion fatigue. If not addressed, compassion fatigue may have personal and organizational consequences. Methods Using a descriptive, correlational design, a convenience sample of 268 nurses completed a web-based survey. Results High compassion satisfaction and moderate to low burnout and secondary traumatic stress were described by 49% of participants. Education was statistically associated with burnout and secondary traumatic stress. Life stress scores were significantly associated with age, experience, organizational tenure, and professional engagement. Narrative commentary yielded 5 themes: staffing, recognition, boundaries, expectations, and hopelessness. Organizational initiatives to prevent or mitigate compassion fatigue focused on awareness, balance, and connections. Conclusions Nurses are negatively impacted by the emotional cost of caring. Future studies need to identify interventions to minimize compassion fatigue.

BACKGROUND: Noninvasive ventilation (NIV) is commonly used in neonates. A mode of NIV called neurally adjusted ventilatory assist (NAVA) offers patient-ventilator interactions by using electrical activity of the diaphragm to control mechanical breaths. We hypothesized that the work of breathing (WOB) would decrease with NIV-NAVA. Secondary objectives evaluated the impact of NIV-NAVA on arterial blood gases and respiratory parameters. METHODS: We compared WOB between synchronized breaths in NIV-NAVA and NIV in piglets with healthy lungs and then with surfactant-depleted lungs. Neonatal pigs (median, 2.0 [range, 1.8–2.4] kg) with healthy and then surfactant depleted lungs were sedated and ventilated with NIV-NAVA and NIV in random order. Airway flow and pressure waveforms were acquired. Waveforms were analyzed for the pressure-time product that reflected WOB. The primary outcome between modes was assessed with repeated measurement analysis of variance. RESULTS: The pressure-time product was significantly decreased for NIV-NAVA in both healthy and injured lungs (P CONCLUSIONS: Synchronized breaths during NIV-NAVA resulted in decreased WOB compared with synchronized breaths during NIV.

Background: The glucose concentrations and times to nadir for newborns of all gestational ages when intrapartum glucose-containing solutions are not routinely provided are unknown. Objective: To characterize and compare patterns of initial glucose concentration nadirs by gestational-age groups. Methods: A cross-sectional cohort study of 1,366 newborns born in 1998 at the University of Arkansas for Medical Sciences, appropriate for gestational age, nonasphyxiated, nonpolycythemic, and not infants of diabetic mothers, were included. Initial plasma glucose concentrations, before intravenous fluids or feedings, were plotted against time after birth for 4 gestational-age groups (full term [FT], ≥37–42 weeks; late preterm [LPT], ≥34 and < 37 weeks; preterm [PT], ≥28 and < 34 weeks; and extremely low gestational age newborns [ELGAN], 23 and < 28 weeks of gestation). Results: ELGAN had the earliest nadir at 61 ± 4 min, followed by PT newborns (71 ± 2 min), and then LPT and FT newborns at 92–93 min. The time to nadir for ELGAN and PT newborns was significantly earlier than for FT newborns. Glucose nadir concentrations for ELGAN, PT, and LPT newborns were significantly lower than for FT newborns. LPT newborns’ pattern of glucose paralleled those of FT newborns, with values approximately 5–6 mg/dL lower during the first 3 h. Conclusion: Plasma glucose nadirs occurred at different times among gestational-age groups during the early postnatal period as follows: ELGAN < PT < LPT ≈ FT. In order to potentially prevent low glucose concentrations at the time of the nadir, exogenous glucose should be provided to all newborns as soon as possible after birth.

There is growing interest in the Kaiser early-onset sepsis (EOS) risk calculator though institutions are hesitant to deviate from the Centers for Disease Control and Prevention guidelines and implement this in their hospitals. We describe the process of implementing routine use of the risk calculator in term and late preterm newborns delivered to mothers with chorioamnionitis in a level III neonatal intensive care unit (NICU). A retrospective chart review of infants delivered to mothers with chorioamnionitis from 2011 to 2014 was performed. Implementation of routine use of the calculator began in January 2015; preintervention and postintervention data were analyzed after a 9-month period of routine use. Following implementation, NICU admission rates, number of blood cultures drawn, and rates of antibiotic use dropped by 54%, 42%, and 59%, respectively ( P < .001). No negative outcomes were reported. In this article, we describe how the calculator was safely implemented in our NICU while decreasing the number of interventions.

Objectives Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance. Efforts to mask flavours often result in poorly controlled, heterogeneous particle distributions and can provide ineffective taste masking. The present work utilized a novel drug delivery technology developed by Orbis Biosciences, Inc., to create an oral taste-masked formulation of prednisone. Methods The study examined the palatability of Orbis’ microsphere prednisone formulation in healthy young adults (n = 24). Four test articles were used in the study including a reference formulation (Roxanne Laboratories), a control and the test formulation (Orbis) prepared in two different ways. Study participants were randomized in a crossover design. Key findings Results indicated that the test prednisone formulation was indistinguishable from the control, and both were preferable to the reference formulation in every category of palatability assessed using a validated 9-point Hedonic Scale. The data also suggested that preparing the microsphere suspension immediately before administration results in the most ideal palatability properties. Conclusions In conclusion, the novel microsphere formulation technology was effective in taste-masking prednisone.

Background Pediatric abdominal pain is challenging to diagnose and often results in unscheduled return visits to the emergency department. External pressures and diagnostic momentum can impair physicians from thoughtful reflection on the differential diagnosis (DDx). We implemented a diagnostic time-out intervention and created a scoring tool to improve the quality and documentation rates of DDx. The specific aim of this quality improvement (QI) project was to increase the frequency of resident and attending physician documentation of DDx in pediatric patients admitted with abdominal pain by 25% over 6 months. Methods We reviewed a total of 165 patients admitted to the general pediatrics service at one institution. Sixty-four history and physical (H&P) notes were reviewed during the baseline period, July–December 2017; 101 charts were reviewed post-intervention, January–June 2018. Medical teams were tasked to perform a diagnostic time-out on all patients during the study period. Metrics tracked monthly included percentage of H&Ps with a ‘complete’ DDx and quality scores (Qs) using our Differential Diagnosis Scoring Rubric. Results At baseline, 43 (67%) resident notes and 49 (77%) attending notes documented a ‘complete’ DDx. Post-intervention, 59 (58%) resident notes and 69 (68%) attending notes met this criteria. Mean Qs, pre- to post-intervention, for resident-documented differential diagnoses increased slightly (2.41–2.47, p = 0.73), but attending-documented DDx did not improve (2.85–2.82, p = 0.88). Conclusions We demonstrated a marginal improvement in the quality of resident-documented DDx. Expansion of diagnoses considered within a DDx may contribute to higher diagnostic accuracy.

Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR). Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AM Results: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR. Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.

Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS). Method: Male neonatal Wistar rats were divided into six groups including control + ddH2O, MS + ddH2O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC. Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats. Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway.

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.

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 (

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.

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.

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

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.

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