Frontiers in Pediatrics

Published by Frontiers
Online ISSN: 2296-2360
Publications
Aims and objective: To determine normal blood pressure (BP) in apparently healthy, asymptomatic school children in the age group of 6-16 years and to determine the correlation of BP values with different sex, weight, height, and body mass index (BMI) and also to find out prevalence of hypertension in school going population. Materials and methods: This prospective, observational study enrolled 3,302 urban children (1,658 boys and 1,644 girls) in the age group of 6-16 years. These were analyzed to study the distribution pattern of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at different ages, sex, weight, height, and BMI. The SBP and DBP were noted as per age and sex. The association was seen between mean SBP and mean DBP with weight, height, and BMI. Information was collected about the family history of hypertension and was correlated with the obtained SBP and DBP readings. Results: The mean SBP in males at 6 years was 99.69 ± 3.62 mm of Hg, at 10 years was 102.20 ± 2.16 mm of Hg, and at 16 years was 115.33 ± 1.26 mm of Hg. The mean SBP in females at 6 years was 96.55 ± 2.86 mm of Hg, at 10 years was 101.16 ± 2.12 mm of Hg, and at 16 years was 112.41 ± 1.06 mm of Hg. The correlation coefficient for relationship between age and SBP in males and females was 0.89 and 0.91, respectively, and for DBP was 0.92 and 0.90, respectively. The correlation coefficient for relationship between height and SBP in males and females was 0.91 and 0.93, respectively, and for DBP was 0.92 and 0.88, respectively. The correlation coefficient for relationship between weight and SBP in males and females was 0.92 and 0.92, respectively, and for DBP was 0.94 and 0.91, respectively. In the nomogram obtained in the study, 95% of study population fall between mean +2SD and -2SD. Conclusion: The blood pressure (BP) (SBP and DBP) tends to increase with age, weight, height, and BMI. The BP values (SBP and DBP) increases grossly after 11 years of age. The students with positive family history of hypertension had higher valve when compared to other student. The BP of children and adolescents can be evaluated using the reference table according to age. The table provided helps to classify as "normal" or "hypertension" (>+2SD).
 
Age (in hours) at which medications were commenced for NAS within the three groups.
Breast milk has been reported to ameliorate the severity and outcome of neonatal abstinence syndrome (NAS). The mechanism of this beneficial effect of breast milk on NAS remains unclear, as the negligible amount of methadone transmitted via breast milk is unlikely to have an impact on NAS. The aim of this study was to compare the impact of different feeding modalities on the onset of NAS. A retrospective medical record review was conducted on 194 methadone-maintained mother/infant dyads. Infants were categorized on the first 2 days of life as predominantly breastfed, fed expressed human breast milk (EBM), or formula fed. The feeding categories were then analyzed using the onset of NAS as the outcome measure. After adjusting for confounders, there was no significant effect of the modality of feeding on the rates of NAS requiring treatment (p = 0.11). Breastfeeding significantly delayed the onset of NAS (p = 0.04). The act of breastfeeding in the first 2 days of life had no effect on whether an infant required treatment for NAS when compared to those fed EBM or formula. This only suggests that the advantages of breastfeeding on NAS cannot be substantiated in a small cohort and should not discourage breastfeeding.
 
A) Right atrial thrombus on echocardiography. (B) CTPA showing bilateral arterial filing defects. (C) Venogram showing complete obstruction of right subclavian vein.
Increased vigilance needed for the detection of thrombotic complications of central venous access in adolescent cystic fibrosis patients Nandini Kandamany*, Basil Elnazir and Peter Greally • Paediatric Cystic Fibrosis Department, Adelaide and Meath National Children’s Hospital, Tallaght, Dublin, Ireland An 18-year-old Caucasian male CF patient (ΔF508/G551D) with pancreatic insufficiency, CF-related liver disease, and impaired glucose tolerance had an indwelling CVC inserted into his right internal jugular vein. This was his eighth catheter in 7 years. A week post-insertion, it was noted to be difficult to draw blood from this catheter. A venogram was subsequently performed, which showed a right internal jugular venous thrombus, with very poor flow through his right subclavian and external jugular veins. The catheter was removed and a right femoral venous catheter was inserted under radiological guidance with difficulty due to poor venous flow. He was treated with anti-coagulants. A 15-year-old Caucasian male with G551D/n CT, pancreatic insufficiency and a PEG in situ presented to hospital with dyspnea, a non-productive cough and reduced exercise tolerance. His oxygen saturations were 88% in room air. There were no focal crepitations detected and air entry was equal bilaterally. His routine blood results were all within the normal ranges including a coagulation screen. No pneumothorax was noted on chest X-Ray. His chest Port-A-Cath appeared to be functioning well. He was admitted and intravenous antibiotics were commenced. A high-resolution CT scan showed chronic CT changes and right-sided volume loss.
 
Bloodstream infection (BSI) is one of the significant causes of morbidity and mortality encountered in a neonatal intensive care unit, especially in developing countries. Despite the implementation of infection control practices, such as strict hand hygiene, the BSI rate in our hospital is still high. The use of a closed catheter access system to reduce BSI related to intravascular catheter has hitherto never been evaluated in our hospital. To determine the effects of closed catheter access system implementation in reducing the BSI rate in preterm neonates with low birth weight. Randomized clinical trial was conducted on 60 low birth weight preterm infants hospitalized in the neonatal unit at Cipto Mangunkusumo Hospital, Jakarta, Indonesia from June to September 2013. Randomized subjects either received a closed or non-closed catheter access system. Subjects were monitored for 2 weeks for the development of BSI based on clinical signs, abnormal infection parameters, and blood culture. Closed catheter access system implementation gave a protective effect toward the occurrence of culture-proven BSI (relative risk 0.095, 95% CI 0.011-0.85, p = 0.026). Risk of culture-proven BSI in the control group was 10.545 (95% CI 1.227-90.662, p = 0.026). BSI occurred in 75% of neonates without risk factors of infection in the control group compared to none in the study group. The use of a closed catheter access system reduced the BSI in low birth weight preterm infants. Choosing the right device design, proper disinfection of device, and appropriate frequency of connector change should be done simultaneously.
 
A representative example of the CIMVA fHRV analysis of RMSSD at (top) 1000 Hz and (bottom) 4 Hz. Note the gradual rise of RMSSD with worsening acidemia (pH decreasing) and an overestimation of RMSSD at baseline in 4 Hz sampled fHRV. Mild, mod and sev = mild, moderate, and severe UCO series, respectively.
FHRV analysis of RMSSD changes during worsening acidemia (black) at 1000 Hz and (gray) 4 Hz sampling rates. Animals reached pH nadir <7.00 between the time points “severe UCO 40 min” and “severe UCO 100 min.” Accordingly, sample sizes of these time points were lower where indicated. For other time points, N = 9. Mean ± SEM. *p < 0.05 versus baseline for 1000 Hz sampled fHRV; # versus baseline for 4 Hz sampled fHRV.
Background: To evaluate the impact of sampling rate on the predictive capability of continuous fetal heart rate (FHR) variability (fHRV) monitoring for detecting fetal acidemia during labor, we tested the performance of the root mean square of successive differences (RMSSD) in R-R intervals from the ECG when acquired with the sampling rate of 4 Hz currently available in FHR monitors, in comparison to the gold standard of 1000 Hz. Methods: Near-term ovine fetuses (N = 9) were chronically prepared with precordial electrodes for recording ECG, vascular catheters for blood sampling, and an umbilical cord occluder. For 1 min every 2.5 min, animals underwent mild partial umbilical cord occlusions (UCO) × 1 h, moderate partial UCO × 1 h, then complete UCO × 2 h, or until arterial pH reached <7.00. Arterial blood samples were drawn at baseline and every 20 min during the UCO series. RMSSD was calculated continuously in 5 min windows using an automated, standardized system (CIMVA.com). RESULTS are presented as mean ± SEM with significance assumed for p < 0.05. Results: Repetitive UCO resulted in pH decreasing from 7.35 ± 0.01 to 7.00 ± 0.03. In all nine animals, RMSSD increased from 16.7 ± 1.0 ms at baseline to 44.4 ± 2.3 ms, 70 ± 15 min prior to reaching the pH nadir when sampled at 1000 Hz. When sampled at 4 Hz, RMSSD at baseline measured 36.1 ± 6.0 ms and showed no significant increase during the UCO series until the pH nadir was reached. Consequently, early detection of severe hypoxic-acidemia would have been missed in all fetuses. Conclusion: RMSSD as a measure of fHRV when calculated from FHR sampled at 1000 Hz allowed for the early detection of worsening hypoxic-acidemia in each fetus. However, when calculated at the low sampling rate of 4 Hz used clinically, RMSSD remained unchanged until terminally when the nadir pH was reached. For early detection of fetal acidemia during labor, more sensitive means of acquiring FHR are therefore recommended than currently deployed, e.g., trans-abdominal fetal ECG.
 
Clinical course of the presented subject and his family history. The triangle indicates the day of specimen collection for the subject. Detected pathogens were indicated above each triangle. Days post-onset refer to the time-course of symptoms in the subject. Please see the main text for details. Abbreviations: HHV-6, human herpesvirus type-6; EV68, enterovirus 68; HPeV, human parechovirus; CVA6, coxsachievirus A6; MDZ, midazolam; mPSL, methylpredonisolone; EDV, edaravone; RhV, rhinovirus; and Echo18, echovirus 18.
Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE.
 
Cascade of inflammatory pathway in brain after acute HI. Resting microglia get activated to M1 type through classical pathway and M2 type through alternate pathway. M1 microglia release inflammatory cytokines, which cause disruption of blood–brain barrier (BBB). The BBB disruption promotes infiltration of macrophages, which further release inflammatory cytokines. Active microglia and macrophages release reactive oxygen species (ROS) and reactive nitrogen species (RNS), which contribute to the secondary neuronal injury. M2 microglia release trophic factors, which contribute to the neuronal repair. TNF-α, a potent proinflammatory cytokine contributes to peripheral immune cell recruitment and proliferation in the brain, neuronal apoptosis, oligodendrocytes, and axonal injury after HI (94). IL-1β blocks oligodendrocyte proliferation (95) and elevates levels of circulating IL-6, another potent cytokine that contributes to early neurologic deterioration after brain ischemia (95, 96). Matrix metalloproteinases (MMPs) disrupt the BBB and allow peripheral leukocyte infiltration (97). Macrophage colony stimulating factor (MCSF), released mainly by macrophages, T cells, B cells, and microglia, induces proliferation, migration, and activation of microglia and regulates the release of proinflammatory cytokines from macrophages (98, 99). MCP-1, a chemokine secreted by active microglia and astrocytes in response to injury (100), mediates the migration of microglia, monocytes, and lymphocytes to the site of injury in the CNS (101, 102).
|The M1 (classical) and M2 (alternate) phenotypes of microglia.
Whole-body hypoxia-ischemia activates central and peripheral immune components. The whole-body HI not only induces neuroinflammation and necrosis and apoptosis in brain but also potentially exerts different effects in peripheral immune organs like spleen, which is influenced by the autonomic nervous system. Microglial activation after global HI leads to secondary neuronal injury. The cytokines and chemokines released by activated microglia, astrocytes, mast cells, and peripheral immune cells cause secondary neuronal damage, degrade BBB for leukocyte recruitment from blood stream, and eventually also contribute to tissue repair. Primed and polarized T cells enter CNS in response to HI, recognize neuronal surface receptors like major histocompatibility complex, and interact with damaged neurons for repair. Macrophages and neutrophils also enter the CNS in response to HI for clearance of debris. Under pathologic conditions, neurotransmitter and neuroinflammatory substances interact with peripheral immune system for priming and activating immunologic pathways for clearance of pathogen and/or debris. Due to cross talk between peripheral and central immune systems, the effects of peripheral immune organs like thymus, liver, spleen, gut associated lymphoid tissues and bone marrow on neuroinflammation, and secondary neuronal injury after whole-body HI need to be studied. Mic, microglia; N, neuron; A, astrocyte; Mas, mast cell; Mac, macrophage; Tc, T cell; Neu, neutrophil; T, thymus; TD, thoracic duct; L, liver; S, spleen; GALT, gut-associated lymphoid tissue; BM, bone marrow.
Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia - the so-called "brain macrophages," infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds.
 
Histopathological findings – Aschoff nodules (arrows) in samples of myocardium from the papillary muscles of the excised mitral valve (A). The arrows in sample (B) indicate Anitschkow cells. Photo courtesy of Dr. Lea M. M. F. Demarchi from the Laboratory of Pathology, Heart Institute (InCor), University of São Paulo Medical School.
| Frequency of Aschoff bodies in specimens obtained after elective cardiac surgery in various reports.
Rheumatic fever (RF) remains endemic in many countries and frequently causes heart failure due to severe chronic rheumatic valvular heart disease, which requires surgical treatment. Here, we report on a patient who underwent an elective surgical correction for mitral and aortic valvular heart disease and had a post-operative diagnosis of acute rheumatic carditis. The incidental finding of Aschoff bodies in myocardial biopsies is frequently reported in the nineteenth-century literature, with prevalences as high as 35%, but no clinical or prognostic data on the patients is included. The high frequency of this finding after cardiac surgery in classical reports suggests that these patients were not using secondary prophylaxis for RF. We discuss the clinical diagnosis of acute rheumatic myocarditis in asymptomatic patients and the laboratorial and imaging methods for the diagnosis of acute rheumatic carditis. We also discuss the prognostic implications of this finding and review the related literature.
 
Six scenarios were held fortnightly and then each was repeated once over the next 3 months. Participants were assessed by two questionnaires (A and B), one initially and one 6 months after completion of scenario sessions.
| Simulated critical case descriptions.
| Baseline characteristics of participants in the simulation study.
| Regression analysis of post-scenario confidence levels.
Objectives Nationally accredited simulation courses such as Advance Paediatric Life Support (APLS) and Pediatric Advance life support (PALS) are recommended for health care professionals (HCPs) at 2 yearly intervals as a minimum requirement, despite literature evidence suggesting rapid decline in knowledge shortly after course completion. The objective of this study was to evaluate an observation-based, educational intervention program aimed at improving previously acquired knowledge and confidence in managing critical illnesses. Methods A prospective cohort longitudinal study was conducted over a 6 month period. Participants were assessed with a knowledge based questionnaire immediately prior to and after observing 12 fortnightly critical illness scenario demonstrations (CISD). The outcome measure was performance on questionnaires. Regression analysis was used to adjust for potential confounders. Questionnaire practice effect was evaluated on 30 independent HCPs not exposed to the CISDs. Results Fifty-four HCPs (40 doctors and 14 nurses) participated in the study. All participants had previously attended nationally accredited simulation courses with a mean time since last attendance of 1.8 ± 0.4 years. The median number of attendances at CISD was 6 [2-12]. The mean questionnaire scores at baseline (17.2/25) were significantly lower than the mean post intervention questionnaire scores (20.3/25), p=0.003. The HCPs self-rated confidence in managing CISD was 6.5 times higher at the end of the program in the intervention group (p=0.002) than at baseline. There was no practice effect for questionnaires demonstrated in the independent sample. Conclusions The educational intervention program significantly improved the knowledge and confidence of the participants in managing paediatric critical illnesses. The CISD program provides an inexpensive, practical and time effective method of facilitating knowledge acquisition and retention. Despite the dis
 
Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of social enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or social enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by social enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p, and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, glutamate, and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression.
 
Influence of vasodilatory agents on pulmonary and systemic arterial pressures. The mean pulmonary arterial pressures and the mean systemic arterial pressures for 13 patients during five phases of heart catheterization are shown. The mean pulmonary arterial pressure was lower during oxygen with nitric oxide and baseline 1 (*p < 0.05). The mean systemic arterial pressure during treatment with an intravenous infusion of sildenafil was lower than the mean systemic arterial pressure during oxygen, oxygen with nitric oxide, and baseline 2 (*p < 0.05). The corresponding mean pulmonary arterial wedge pressures are shown in black with the mean pulmonary arterial pressures. The corresponding right atrial pressures are shown in black with the mean systemic arterial pressures.
Differences in the pulmonary vasodilatory effects for oxygen with nitric oxide and sildenafil. The percent decrease in pulmonary vascular resistance with oxygen and nitric oxide and the percent decrease in pulmonary vascular resistance with sildenafil for each patient are shown. There is no linear correlation for the pulmonary vasodilatory effects of these agents (r2 = 0.011, p = 0.738). There is no correlation for patients with an initial baseline mean pulmonary arterial pressure ≥35 mm Hg (dark circles) or for patients with an initial baseline mean pulmonary arterial pressure <35 mm Hg (light circles). Rp, pulmonary vascular resistance index.
| Arterial blood gases, heart rate, blood flow, and vascular resistance.
A Bland Altman plot for the comparison between differences in the percent decrease in pulmonary vascular resistance for oxygen with nitric oxide and sildenafil. There is statistical evidence of agreement between the pulmonary vasodilatory effects for oxygen with nitric oxide and sildenafil. The mean difference between the percent decrease in pulmonary vascular resistance for oxygen with nitric oxide and sildenafil is −2.8 (solid line). All values fall within the 95% confidence intervals (±1.96 standard deviations, dashed lines). However, the difference between the percent decrease for oxygen with nitric oxide and sildenafil exceeds 20% for 7 of the 13 patients. This appears to be true for patients with an initial baseline mean pulmonary arterial pressure ≥35 mm Hg (dark circles) and for patients with an initial baseline mean pulmonary arterial pressure <35 mm Hg (light circles). Rp, pulmonary vascular resistance index.
| Number of responsive patients.
Objective: Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to long-term vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods: A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21-53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21-51% oxygen, and 21-51% oxygen with 0.05-0.29 mg/kg intravenous sildenafil) of the procedures were compared using analysis of variance. A linear regression analysis and a Bland Altman plot were used to compare the percent change in mean pulmonary arterial pressure and the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil. Results: Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide and 21-51% oxygen with sildenafil. Pulmonary blood flow during sildenafil was greater than pulmonary blood flow during 100% oxygen and 100% oxygen with nitric oxide. The pH, right atrial pressure, and left atrial pressure did not change during the five phase of heart catheterization. Mean pulmonary arterial pressure (millimeter of mercury, mean ± standard error of the mean) was 38 ± 4 during 21-53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21-51% oxygen, and 32 ± 2 during 21-51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r (2) = 0.011, p = 0.738). The Bland Altman analysis demonstrated statistical agreement between the effects of oxygen with nitric oxide and sildenafil. However, differences were large enough to limit the interchangeable use of these vasodilators in a clinical setting. Conclusion: Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide do not reliably predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.
 
| Correlations with quality of life in adolescents with diabetes or juvenile rheumatoid arthritis at T2 (2011): parents' perceptions. 
Purpose: To (i) investigate the influence of general self-efficacy on quality of life outcomes over time among adolescents with type I diabetes or juvenile rheumatoid arthritis (JRA), (ii) investigate parents’ perceptions of general self-efficacy and quality of life of adolescents with diabetes or JRA over time, and (iii) identify possible differences in the evaluations of adolescents and parents. Methods: This study included adolescents aged 12–25 years with type I diabetes or JRA and their parents. At T1, 171/573 (30% response rate) adolescents with diabetes or JRA and 229/563 (41% response rate) parents completed the questionnaire. At T2, 230/551 (42% response rate) adolescents and 220/559 (39% response rate) parents still participating in the study completed the questionnaire. A total of 112 adolescents and 143 parents filled in the questionnaires at both T1 and T2. Results: Adolescents perceived significant improvement in their general self-efficacy and reduced quality of life over time, whereas parents’ perceptions did not change. According to adolescents and parents, physical functioning was better among adolescents with diabetes than among those with JRA. Regression analyses of adolescents’ data showed that general self-efficacy at T1 (β = 0.13; p ≤ 0.10) and changes in general self-efficacy (β = 0.22; p ≤ 0.01) predicted quality of life at T2. Parents’ responses revealed that adolescents’ general self-efficacy at T1 (β = 0.16; p ≤ 0.05) and changes in adolescents’ general self-efficacy (β = 0.18; p ≤ 0.05) predicted adolescents’ quality of life at T2. Conclusion: General self-efficacy and changes therein positively affected quality of life in adolescents with diabetes or JRA over time, as perceived by adolescents and parents. These findings emphasize the need for the implementation of interventions aiming to improve general self-efficacy in these populations.
 
| Effect of family types (intact vs. non-intact) on positive youth development, psychological well-being, and adolescent behaviors. 
This study investigated whether Chinese adolescents living in intact and non-intact families differed in their positive development, life satisfaction, and risk behavior. A total of 3,328 Secondary 1 students responded to measures of positive youth development (such as resilience and psychosocial competencies), life satisfaction, and risk behavior (substance abuse, delinquency, Internet addiction, consumption of pornographic materials, self-harm, and behavioral intention to engage in problem behavior). Findings revealed that adolescents growing up in intact families reported higher levels of positive developmental outcomes and life satisfaction as compared with adolescents from non-intact families. Adolescents in non-intact families also reported higher levels of risk behaviors than those growing up in intact families.
 
| Demographic, laboratory, and sleep parameters of the subjects. 
| Laboratory and PSG parameters of the 15 subjects before and after treatment. 
Objective: This study aimed to evaluate circulating natriuretic peptides (NP) concentration in obese and non-obese children and adolescents with and without obstructive sleep apnea (OSA), and their levels following OSA treatment. Methods: Subjects with habitual snoring and symptoms suggestive of OSA were recruited. They underwent physical examination and overnight polysomnography (PSG). OSA was diagnosed if obstructive apnea–hypopnea index (OAHI) was ≥1/h. Fasting serum atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were taken after overnight PSG. The subjects were divided into obese, non-obese, with and without OSA groups for comparisons. Results: One hundred fourteen children (77 were boys) with a median [interquartile range (IQR)] age of 10.8 (8.3–12.7) years (range: 2.4–11.8 years) were recruited. Sixty-eight subjects were found to have OSA. NP levels did not differ between subjects with and without OSA in both obese and non-obese groups. Stepwise multiple linear regressions revealed that body mass index (BMI) z-score was the only independent factor associated with NP concentrations. Fifteen children with moderate-to-severe OSA (OAHI >5/h) underwent treatment and there were no significant changes in both ANP and BNP levels after intervention. Conclusion: Body mass index rather than OSA was the main determinant of NP levels in school-aged children and adolescents.
 
Objectives/hypothesis: Congenital aural atresia is a rare condition affecting 1 in 10,000–20,000 children a year. Surgery is required to restore hearing to facilitate normal development. The objective of this study was to compare outcomes in hearing, complications, and quality of life of surgical reconstruction of the external auditory canal reconstruction (EACR) and bone-anchored hearing aid (BAHA) in a pediatric population with congenital aural atresia. Study design: Subjects were children who had a diagnosis of congenital aural atresia or stenosis and who received either BAHA or EACR. Methods: The medical records of 68 children were reviewed for operative complications and audiometric results. A quality of life questionnaire was prospectively administered to a subset of subjects. Results: Pre-operatively, air conduction threshold was not significantly different between groups at 500, 1000, 2000, and 4000 Hz (p > 0.05). Post-operatively, the BAHA group (44.3 ± 14.3 and 44.5 ± 11.3) demonstrated a significantly larger hearing gain than the EACR group (20.0 ± 18.9 and 15.3 ± 19.9) in both the short and long-term periods (p < 0.001). Overall, the incidence of complications and need for revision surgery were comparable between groups (p > 0.05). Quality of life assessment revealed no statistical significance between the two groups (p > 0.05). Conclusion: Although the quality of life and incidence of surgical complications between the two interventions was not significantly different, BAHA implantation appears to provide a better, more reliable audiologic outcome than EACR.
 
| Summary of data subdivided by gender.
Correlation between Cobb angle and FVC.
Lack of correlation between Cobb angle and age.
Historically, thoracic kyphosis has been reported to be common amongst patients with cystic fibrosis (CF). The mechanisms leading to the development of this abnormality of the chest wall are not fully understood. In order to explore the prevalence of the condition amongst children with CF in the early twenty-first century and to explore factors that might be contributing to its development, a retrospective cross sectional study was undertaken in a regional CF unit. Data were obtained from 74 children with CF aged 8-16 years attending for their annual review. Thoracic kyphosis was measured from lateral chest X-ray using an alternative Cobb method. Lung function, disease severity, and nutritional status were also recorded. Correlations between measures were explored using a multiple linear regression model. The range of Cobb angles measured was 5.4-44.3° with thoracic kyphosis identified in only two subjects. There was no correlation between age and thoracic kyphosis, however, there was a significant correlation between lung function and thoracic kyphosis (p = 0.004). Regression coefficient (b) was -0.26 (95% CI: -0.44, -0.08). The prevalence of thoracic kyphosis is significantly less amongst children with CF than previously reported. This appears likely to be associated with the overall improvements in pulmonary status. Studies of older populations may bring further understanding of increasing thoracic kyphosis in people with CF.
 
Congenital adrenal hyperplasia (CAH) most commonly due to 21-hydroxylase deficiency is the most common type of disorder of sex development. This review will focus on CAH addressing historical and current surgical techniques with their anatomical foundations, with special attention to long-term results and outcomes on sexual function, patient satisfaction, patient attitude toward surgery, and ongoing controversies in management of these patients.
 
| Demographic information of participants (N = 114). 
| Results from the factor analysis. 
| Factor loadings. 
| Cronbach's Alpha scores. 
Parenting anticipatory guidance is one way to promote optimal child health and development and minimize disparities between children from lower socio-economic status families and their higher income peers. However, low rates of attendance at and completion of parenting programs has been demonstrated. Understanding barriers to participation has important implications. The Obstacles to Engagement Scale (OES) has been used in some populations but it has not been evaluated for use with low-income African American samples. The aim of the current study is to evaluate the factor structure of the OES with a sample of low-income, African American parents. Parents or legal guardians with children aged 3-8 years completed a survey in the waiting room of a primary care pediatric academic practice in an urban location in the southern United States of America (N = 114). Almost 87% had <12th grade education and 93% of the children received Medicaid services. The OES was one measure from a larger study and only participants with complete data on the OES were included in the exploratory factor analysis (EFA). The EFA did not support the previous 4-factor solution (intervention demands, personal or family stressors or obstacles, relevance of or trust in intervention, and time and scheduling demands. Instead, a 3-factor statistical solution emerged but not all items held together conceptually. The current study supports the necessity for evaluating study instruments for use with specific populations. Larger samples are needed to disentangle the effects of educational and poverty status from race and ethnicity and to develop and validate instruments that are appropriate for the study population.
 
| Description of participants. 
Childhood obesity is a growing problem for children in the United States, especially for children from low-income, African American families. The purpose of this qualitative study was to understand facilitators and barriers to engaging in healthy lifestyles faced by low-income African American children and their families. This qualitative study used semi-structured focus group interviews with eight African American children clinically identified as overweight or obese (BMI ≥ 85) and their parents. An expert panel provided insights in developing culturally appropriate intervention strategies. Child and parent focus group analysis revealed 11 barriers and no definitive facilitators for healthy eating and lifestyles. Parents reported confusion regarding what constitutes nutritional eating, varying needs of family members in terms of issues with weight, and difficulty in engaging the family in appropriate and safe physical activities; to name a few themes. Community experts independently suggested that nutritional information is confusing and, often, contradictory. Additionally, they recommended simple messaging and practical interventions such as helping with shopping lists, meal planning, and identifying simple and inexpensive physical activities. Childhood obesity in the context of low-resource families is a complex problem with no simple solutions. Culturally sensitive and family informed interventions are needed to support low-income African American families in dealing with childhood obesity.
 
Background: Mucus transport mediated by motile cilia in the airway is an important defense mechanism for prevention of respiratory infections. As cilia motility can be depressed by hypothermia or exposure to anesthetics, in this study, we investigated the individual and combined effects of dexmedetomidine (dex), fentanyl (fen), and/or isoflurane (iso) at physiologic and low temperatures on cilia motility in mouse tracheal airway epithelia. These anesthetic combinations and low temperature conditions are often used in the setting of cardiopulmonary bypass surgery, surgical repair of congenital heart disease, and cardiac intensive care. Methods: C57BL/6J mouse tracheal epithelia were excised and cilia dynamics were captured by videomicroscopy following incubation at 15, 22–24, and 37°C with different combinations of therapeutic concentrations of dex (10 nM), fen (10 nM), and iso (0.01%). Airway ciliary motion was assessed and compared across conditions by measuring ciliary beat frequency and ciliary flow velocity. Statistical analysis was carried out using unpaired t-tests, analysis of variance, and multivariate linear regression. Results: There was a linear correlation between cilia motility and temperature. Fen exerted cilia stimulatory effects, while dex and iso each had ciliodepressive effects. When added together, fen + iso, dex + iso, and dex + fen + iso were all cilia inhibitory. In contrast fenl + dex did not significantly alter ciliary function. Conclusion: We show that ciliary motility is stimulated by fen, but depressed by dex or iso. However, when used in combination, ciliary motility showed changes indicative of complex drug–drug and drug–temperature interactions not predicted by simple summation of their individual effects. Similar studies are needed to examine the human airway epithelia and its response to anesthetics.
 
Enzymatic reactions catalyzed by PLD. PLD is associated with membrane receptors including G-protein coupled receptors (GPCR), receptor tyrosine kinases, or integrins, which all activate PLD. Shown is GPCR-coupled PLD, which, upon activation under physiological conditions, hydrolyzes phosphatidylcholine (PC) to produce choline and phosphatidic acid (PA), a lipid second messenger that binds and activates several signaling molecules including RAF, Akt, mTOR, and p70S6K and stimulates several cell functions including proliferation, cell trafficking, and cell survival. The PLD signaling pathway is disrupted by ethanol, which competes with water leading to the formation of phosphatidylethanol (PEth) at the expenses of phosphatidic acid, therefore, inhibiting phosphatidic acid-activated signaling and functions.
A–C) Ethanol-treated astrocytes inhibits hippocampal neuron neurite outgrowth. Hippocampal neurons plated on top of ethanol-pre-treated astrocytes (75 mM) display reduced neurite outgrowth. Shown are representative fields (20×) of neurons incubated with control (A) and ethanol-treated (B) astrocytes; insets show the same fields at a lower magnification (10×). (C) Quantification of the length of the longest neurite and of minor neurite in 60 cells per treatment was carried out using the software Image J. ***p < 0.001, Student’s t test. (D–F) Neonatal ethanol exposure inhibits dendrite outgrowth in PD9 rats. Male rat pups were intubated with 5 g/kg ethanol or were sham (control) intubated from PD4 to PD9 and sacrificed on PD9. The brains were stained using the Golgi-Cox procedure. Representative CA1 neurons in control (D) and ethanol-exposed rats (E) are shown (10×); insets show the same fields at a lower magnification (4×). Dendrite length was measured using the software Neurolucida (F). ***p < 0.001 by Student’s t test. (G–I) Neonatal ethanol exposure reduces dendrite length in PD36 rats. Female rat pups were intubated with 5 g/kg/day of ethanol or were sham (control) intubated from PD4 to PD9 and sacrificed on PD36. Brains were stained using the Golgi-Cox procedure. Shown are representative CA1 hippocampal neurons in control (G) and ethanol-exposed rats (H) (10×); insets show the same fields at a lower magnification (4×). Dendrite length was measured using the software Neurolucida (I). **p < 0.01, Student’s t test.
Model for interactions of astrocytes and neurons in cholesterol clearance and dysregulation by ethanol. (A) Cholesterol is produced by both astrocytes and neurons. Astrocytes produce and release nascent, lipid-poor lipoproteins through the lipidation of apoE via the membrane-bound ABCA1. In the brain parenchyma, nascent lipoproteins stimulate cholesterol efflux through their interaction with ABCA1 and ABCG1 in astrocytes and ABCG4 in neurons. Lipoprotein-associated cholesterol exits the brain through the cerebrospinal fluid. (B) Ethanol upregulates ABCA1 and ABCG1 in astrocytes, and increases the formation of astrocyte lipoproteins, which extract more cholesterol from astrocytes and neurons (pathways upregulated by ethanol are in red). Neurons are sensitive to changes in cholesterol content and, upon protracted induction of cholesterol efflux, decrease their cholesterol content and undergo cell death. Chol, cholesterol.
Representation of the main effects exerted by ethanol on astrocytes, oligodendrocytes, and microglia that may play a role in the neuropathology of FASD.
During the last 20 years, new and exciting roles for glial cells in brain development have been described. Moreover, several recent studies implicated glial cells in the pathogenesis of neurodevelopmental disorders including Down syndrome, Fragile X syndrome, Rett Syndrome, Autism Spectrum Disorders, and Fetal Alcohol Spectrum Disorders (FASD). Abnormalities in glial cell development and proliferation and increased glial cell apoptosis contribute to the adverse effects of ethanol on the developing brain and it is becoming apparent that the effects of fetal alcohol are due, at least in part, to effects on glial cells affecting their ability to modulate neuronal development and function. The three major classes of glial cells, astrocytes, oligodendrocytes, and microglia as well as their precursors are affected by ethanol during brain development. Alterations in glial cell functions by ethanol dramatically affect neuronal development, survival, and function and ultimately impair the development of the proper brain architecture and connectivity. For instance, ethanol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination; furthermore, ethanol induces microglia activation and oxidative stress leading to the exacerbation of ethanol-induced neuronal cell death. This review article describes the most significant recent findings pertaining the effects of ethanol on glial cells and their significance in the pathophysiology of FASD and other neurodevelopmental disorders.
 
The Inflammatory Bowel Diseases (IBDs) are diagnosed more commonly in children and adolescents. Following diagnosis, the key objectives are to achieve and then maintain remission. Although some therapies are able to effectively modify and modulate inflammatory events, none of the available interventions cure these conditions. Consequently, children and their parents face uncertainty and may look to alternative management options as ways to help their child, which may include various complementary and alternative medicines (CAMs). A number of studies have shown that many children with IBD receive or are given CAM agents. This article reviews the rates and patterns of CAM use in children with IBD, and emphasizes the increasing importance of these aspects of the management of children with IBD.
 
The prevalence of developmental disabilities in the young age is of the order of 15%. When behavioral and social-emotional disorders, physical impairments, and sensory disorders are included, the need for special intervention increases to one out of four children. As the sensitivity and specificity of the best screening tests are in the range of 70-80%, their predictive value is controversial. The cost of conducting definitive tests and repeat screening for those who fail the screening tests is high. Children with severe disorders can be identified clinically without a screening test. The poor predictability, difficulty in implementation, and the high costs of developmental testing suggest that children, particularly those in high-risk communities, might be better served by implementing intervention programs for all, instead of trying to identify the outliers through screening.
 
Summary of results of seromuscular colocystoplasty line with urothelium in publications that listed pressure specific BC. 
Alternatives to conventional enterocystoplasty have been developed in order to avoid the most common complications derived from contact of the urine with intestinal mucosa. In this article critically we review the literature on the topics: ureterocystoplasty, detrusorectomy, detrusorotomy, seromuscular gastroenterocystoplasty, use of off the shelf biomaterials, and bladder augmentation by bioengineering. Recognizing the difficulty of deciding when a child with a history of posterior urethral valves requires and augmentation and that the development of a large megaureter in cases of neurogenic dysfunction represents a failure of initial treatment, we conclude that ureterocystoplasty can be useful in selected cases when a large dilated ureter is available. Seromuscular colocystoplasty lined with urothelium (SCLU) has been urodynamically effective in several series when the outlet resistance is high and no additional intravesical procedures are necessary. Seromuscular gastrocystoplasty lined with urothelium seems to offer no distinct advantages and involves a much more involved operation. The use of seromuscular segments without urothelial preservation, with or without the use of an intravesical balloon has been reported as successful in two centers but strict urodynamic evidence of its effectiveness is lacking. The published evidence argues strongly against the use of detrusorectomy or detrusorotomy alone because of the lack of significant urodynamic benefits. Two recent reports discourage the use of small intestinal submucosa patches because of a high failure rate. Finally, research into the development of a bioengineered bladder constructed with cell harvested from the same patient continues but is fraught with technical and conceptual problems. In conclusion of the methods reviewed, only ureterocystoplasty and SCLU have been proven urodynamically effective and reproducible.
 
In recent decades, new research into the developmental defects and pathophysiological basis of congenital diaphragmatic hernia (CDH) has revealed opportunities for the development of innovative therapies. Importantly, the use of animal models to represent this anomaly in the laboratory has resulted in the discovery of many important genetic, epigenetic, and other molecular contributors to this condition. In this review, the most commonly used and newly devised animal models of CDH are presented to familiarize the reader with the latest innovations in the basic sciences.
 
Immunization protocol for the induction of autoimmune valvulitis in Lewis rats and the immunological, histological, and functional changes following immunization with recombinant streptococcal M protein. (A) The induction of valvulitis in the rat autoimmune valvulitis (RAV) model of RF/RHD involves a primary immunization of female Lewis rats (under isoflurane anesthesia) with 500 μg GAS rM5 protein (or PBS as a negative control) in complete Freund’s adjuvant (CFA) administered subcutaneously (s.c.) in the hock on day 0. On days 1 and 3, rats are injected intraperitoneally (i.p.) with an additional adjuvant being either 0.3 μg commercially purchased pertussis toxin [PTx; (7)] or 1010 CFU formalin-killed Bordetella pertussis (6, 8, 9) each in 200 μl PBS. On day 7, rats receive a booster immunization with 500 μg GAS rM5 protein (or PBS as a negative control) in incomplete Freund’s adjuvant (IFA) administered s.c. in the flank under anesthesia. On day 21, the rats are euthansed by CO2 asphyxiation to harvest blood and organs for histological examination of heart tissue and determination of GAS rM5-specific antibody levels and assessment of T cell function. (B) GAS rM5-specific IgG antibodies in rat (n = 5) serum were detected by ELISA. The highest serum dilution that was positive for GAS rM5-specific IgG antibodies (cut-off value 3 SD higher than the mean for the known negative control serum) was recorded as the serum titer. Serum from rats immunized with GAS rM5 contained significantly higher GAS rM5-specific antibodies compared to control (P = 0.007). (C) Proliferative response of GAS rM5-specific T cells from spleens of rats (n = 5) was determined by 3H-thymidine incorporation assay and found to be significantly higher than in controls immunized with PBS (P = 0.009). Bars depict the mean ± SEM. **P ≤ 0.01. Immunohistological changes (D,E) in representative valvular tissue and myocardium (inset) from (D) controls and (E) rM5-immunized animals. Immunohistochemical staining of infiltrating mononuclear cells demonstrates the presence of CD4+ T cells in rM5-immunized animals compared to controls. Scale bar indicates 50 μM (DAB staining). (F) ECG complexes from a control and a rM5-immunized rat demonstrate significantly longer P-R interval in the rM5-immunized rats (Images courtesy of Dr Lisa Chilton, James Cook University). (G) Echocardiographs from control and an rM5-immunized rat demonstrate reduction in fractional shortening due to reduced LV contractility. Bars represent the width of the left ventricle (LV) chamber during contraction (*Images courtesy of Drs Lisa Chilton and Jane Day, James Cook University).
| Immunopathological changes in rodents investigated as models for rheumatic heart disease.
Rheumatic fever (RF) and rheumatic heart disease (RHD) are sequelae of group A streptococcal (GAS) infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unraveled partly due to experimentation on animal models. RF/RHD is a uniquely human condition and modeling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM) and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model. In Lewis rats immunized with rM, the development of hallmark histological features akin to RF/RHD, both in the myocardial and in valvular tissue have been reported, with the generation of heart tissue cross-reactive antibodies and T cells. Recently, a Lewis rat model of Sydenham's chorea and related neuropsychiatric disorders has also been described. Rodent models are very useful for assessing disease mechanisms due to the availability of reagents to precisely determine sequential events following infection with GAS or post-challenge with specific proteins and or carbohydrate preparations from GAS. However, studies of cardiac function are more problematic in such models. In this review, a historical overview of animal models previously used and those that are currently available will be discussed in terms of their usefulness in modeling different aspects of the disease process. Ultimately, cardiologists, microbiologists, immunologists, and physiologists may have to resort to diverse models to investigate different aspects of RF/RHD.
 
INTRODUCTIONSystemic venous anomalies are quite rare and can be associated with congenital heart disease requiring surgery.MATERIALS AND METHODS All consecutive patients (pts) undergoing surgery for congenital heart defects were retrospectively analyzed for presence of systemic venous anomalies: a) persistent left superior vena cava (PLSVC)b) inferior vena cava (IVC) interruptionc) retro-aortic innominate vein. RESULTSFrom 9/2010 to 5/2012 155 pts, median age 7 months, mean age 1.3 years (3days-50years), median weight 4 kg, mean weight 7.2 kg (0.6-110kg) underwent congenital heart surgery. Twenty-nine systemic venous anomalies were identified in 28/155 patients (=18.1%). PLSVC was present in 21 pts (=13.5%), median age 4 months, mean age 2.7 years (3days-22years), median weight 6 kg, mean weight 10.1 kg (2.4-43.0 kg). IVC interruption was identified in 5 pts (=3.2%), median age 2 months, mean age 5.4 years (30days-26years), median weight 3.7kg, median weight 17 kg (2.3-68.0kg). Retro-aortic innominate vein was diagnosed in 3 pts (=1.9%), median age 5 years, mean age 3.7 years (10months-5years), median weight 12 kg, mean weight 10.1 kg (4.5-14kg). Complete pre-operative diagnosis was obtained in 14/28 (=50%) pts with echocardiography and in other 8/28 (=28.6%) only after computed tomography (CT) scan, for a total of 22/28 (=78.6%) correct pre-operative diagnosis. In 6/28 (=21.4%) patients the diagnosis was intra-operative.Total incidence of systemic venous anomalies was 18.1% (vs 4% in the literature, P=0.0009), with presence of PLSVC = 13.5% (vs 0.3-4.0%, respectively P=0.0004 and P=0.0012), IVC interruption = 3.2% (vs 0.1-1.3%,N.S.), and retro-aortic innominate vein = 1.9% (vs 0.2-1%,N.S.).CONCLUSIONS Our study showed an incidence of systemic venous anomalies in Middle Eastern pts with congenital heart defects higher than previously reported. In 78.6% of pts the diagnosis was correctly made before surgery (echocardiography or CT scan), with 21.4%
 
Voiding cystourethrogram (VCUG) showing thickened bladder neck and dilated urethra proximal to the anterior urethral valve.
Male patient with anterior urethral diverticulum. (A) Prenatal ultrasound showing large cystic mass in the genital area. (B) Enlarged urethral bulging mass, megalourethra. (C) Picture depicting anterior urethral valve during open urethroplasty.
Purpose: Anterior urethral valves (AUVs) is an unusual cause of congenital obstruction of the male urethra, being 15-30 times less common than posterior urethral valves (PUVs). It has been suggested that patients with congenital anterior urethral obstruction have a better prognosis than those with PUV, with less hydronephrosis, and a lower incidence of chronic renal insufficiency (5 vs. 30%). The long-term prognosis of AUVs is not clear in the literature. In this report we describe our experience and long-term follow up of patients with anterior urethral valve. Materials and methods: We retrospectively identified 13 patients who presented with the diagnosis of AUVs in our institutions between January 1994 and June 2012. Two patients were excluded: one patient had no follow up after intervention; the other had a follow up <1 year. From the 11 patients included, we evaluated the gestational age, prenatal and postnatal ultrasound findings, voiding cystourethrogram findings, age upon valve ablation, micturition pattern, creatinine, and clinical follow up. Results: Between 1994 and 2012 we evaluated 150 patients with the diagnosis of urethral valves. Of this group, 11 patients (7.3%) had AUVs and an adequate follow up. Mean follow up is 6.3 years (2.5-12 years). Five (45.4%) patients had prenatal diagnosis of AUV. The most common prenatal ultrasonographic finding was bilateral hydronephrosis and distended bladder. One patient showed a large perineal cystic mass, which was confirmed to be a dilated anterior urethra. The mean gestational age was 37.6 weeks (27-40 WGA). Postnatally, 90% had trabeculated bladder, 80% hydronephrosis, and 40% renal dysplasia. The most common clinical presentation was urinary tract infection in five patients (45.4%), followed by weak urinary stream found in four patients (36.3%). The age at initial surgical intervention ranged between 7 days and 13 years. Seven (63.6%) patients had primary transurethral valve resection or laser ablation and three patients (27.2%) had primary vesicostomies. One boy (9.1%) had penile urethrostomy with excision of urethral diverticulum. Two (18.2%) patients developed end-stage renal disease. Conclusion: Anterior urethral valve is a rare congenital entity affecting the genitourinary system in males. Early urinary tract obstruction resulted in end-stage renal disease in 18% of our patient population. In our series, the complication rate and the evolution to renal failure are high and similar to patients with PUV. In patients with AUVs we recommend long-term follow up and close evaluation of patient's bladder and renal function.
 
Atresia of the aortic arch is a rare congenital heart defect with a high mortality when associated with other intracardiac defects. Cardiac magnetic resonance (CMR) provides the exact anatomy of the aortic arch and collateral circulation and is useful to diagnose-associated aortic arch anomalies. This report describes the case of a 4-year-old child with atresia of the aortic arch, referred to our institution with the diagnosis of aortic coarctation and bicuspid aortic valve. On clinical exam, the femoral pulses were not palpable and there was a significant differential blood pressure between the upper and lower limbs. The echocardiography showed a severely stenotic bicuspid aortic valve but was limited for the exact description of the aortic arch. CMR showed absence of lumen continuity between the ascending and descending aorta distal to the left subclavian artery, extending over 5 mm, with the presence of a bend in the arch and diverticulum on either side of the zone of discontinuity, suggesting the diagnosis atresia of the aortic arch rather than coarctation or interruption. The patient benefited from a successful surgical commissurotomy of the aortic valve and reconstruction of the aortic arch with a homograft. The post-operative CMR confirmed the good surgical result. This case emphasizes the utility of CMR to provide good anatomical information to establish the exact diagnosis and the operative strategy.
 
Diagram of intrinsic and extrinsic pathways of apoptosis. (A) In the intrinsic pathway, the proapoptotic BH3-only family members activate Bax or Bak, leading to mitochrondrial outer membrane permeabilization, which drives formation of the apoptosome, activation of the executioner caspases, 3 and 7, and subsequent apoptosis. The proapoptotic BH3-only proteins are inhibited via interactions with the anti-apoptotic Bcl-2 family of proteins. (B) In the extrinsic pathway, ligands such as Fas, tumor necrosis factor (TNF), or tumor necrosis factor-related apoptosis-inducing (TRAIL) ligand bind to death receptors. This results in the recruitment of Fas-associated death domain protein (FADD) and activation of caspase 8. Caspase 8 directly activates caspase 3 and 7. The two pathways interact via caspase 8-mediated cleavage of Bid.
Diagram of kidney development. Kidney development begins with the outgrowth of the ureteric bud (red) from the Wolffian duct into the metanephric mesenchyme (light blue). In response to signals from the ureteric bud, the metanephric mesenchyme condenses around the ureteric bud tip, becoming specified as nephron progenitors (dark blue). Nephron progenitors give rise to multiple cell types of the nephron, including podocytes, proximal tubules, loops of Henle, and distal tubules. The ureteric bud branches in response to signals from the metanephric mesenchyme to form the collecting system of the kidney.
Apoptosis is essential to remodel developing structures and eliminate superfluous cells in a controlled manner during normal development, and continues to be an important component of tissue remodeling and regeneration during an organism's lifespan, or as a response to injury. This mini review will discuss recent studies that have provided insights into the roles of apoptosis in the determination of nephron number and pattern, during normal and abnormal kidney development. The regulation of congenital nephron endowment has implications for risk of chronic kidney disease in later life, whereas abnormalities in nephron pattern are associated with congenital anomalies of the kidney and urinary tract (the leading cause of renal disease in children). Tight regulation of apoptosis is required in normal renal morphogenesis, although many questions remain regarding the regulation of apoptosis by genetic, epigenetic, and environmental factors, in addition to the functional requirement of different components of the apoptotic pathway.
 
| Juvenile myelomonocytic leukemia diagnostic criteria a . 
| Juvenile myelomonocytic leukemia high-risk features. 
Juvenile myelomonocytic leukemia (JMML) is a rare childhood leukemia that has historically been very difficult to confidently diagnose and treat. The majority of patients ultimately require allogeneic hematopoietic cell transplantation (HCT) for cure. Recent advances in the understanding of the pathogenesis of the disease now permit over 90% of patients to be molecularly characterized. Pre-HCT management of patients with JMML is currently symptom-driven. However, evaluation of potential high-risk clinical and molecular features will determine which patients could benefit from pre-HCT chemotherapy and/or local control of splenic disease. Furthermore, new techniques to quantify minimal residual disease burden will determine whether pre-HCT response to chemotherapy is beneficial for long-term disease-free survival. The optimal approach to HCT for JMML is unclear, with high relapse rates regardless of conditioning intensity. An ongoing clinical trial in the Children's Oncology Group will test if less toxic approaches can be equally effective, thereby shifting the focus to post-HCT immunomanipulation strategies to achieve long-term disease control. Finally, our unraveling of the molecular basis of JMML is beginning to identify possible targets for selective therapeutic interventions, either pre- or post-HCT, an approach which may ultimately provide the best opportunity to improve outcomes for this aggressive disease.
 
Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.
 
Pulmonary arterial hypertension (PAH) is a syndrome that is idiopathic in origin or arises in association with a large number of disease processes. Biomarkers for PAH should correlate in some fashion to a hemodynamic measurement such as PA pressure, PA wedge pressure, pulmonary vascular resistance, etc., and/or to a clinical measurement such as survival, pulmonary function test, etc. Since the pathobiology of PAH is multifactorial and complex, it should not be surprising that potential biomarkers will likely reflect aspects of the underlying disease process.
Therapeutic approaches in pediatric pulmonary arterial hypertension (PAH) are based primarily on clinician experience, in contrast to the evidence-based approach in adults with pulmonary hypertension. There is a clear and present need for non-invasive and objective biomarkers to guide the accurate diagnosis, treatment, and prognosis of this disease in children. The multifaceted spectrum of disease, clinical presentation, and association with other diseases makes this a formidable challenge. However, as more progress is being made in the understanding and management of adult PAH, the potential to apply this knowledge to children has never been greater. This review explores the state of the art with regard to non-invasive biomarkers in PAH, with an eye toward those adult PAH biomarkers potentially suitable for application in pediatric PAH.
 
Questionnaire sent to Swiss pediatric infectious diseases specialists following HIV-infected children.
Since the advent of highly active anti-retroviral therapy, HIV-related mortality has decreased dramatically. As a consequence, patients are living longer, and HIV infection is becoming a chronic disease. Patients and caretakers have to deal with chronic complications of infection and treatment, such as cardiovascular diseases, which now represent an important health issue, even in the pediatric population. Prevalence of pulmonary arterial hypertension (PAH) in the adult HIV population is around 0.4-0.6%, which is around 1000- to 2500-fold more prevalent than in the general population. In recent adult PAH registries, HIV has been identified as the fourth cause of PAH, accounting for approximately 6-7% of cases. Therefore, regular screening is recommended in HIV-infected adults by many experts. If HIV-associated PAH is mainly reported in HIV-infected adults, pediatric cases have also been, albeit rarely, described. This scarcity may be due to a very low PAH prevalence, or due to the lack of systematic cardiovascular screening in pediatric patients. As PAH may manifest only years or decades after infection, a systematic screening should perhaps also be recommended to HIV-infected children. In this context, we retrospectively looked for PAH screening in children included in our national Swiss Mother and Child HIV cohort study. A questionnaire was sent to all pediatric infectious disease specialists taking care of HIV-infected children in the cohort. The questions tried to identify symptoms suggestive of cardiovascular risk factors and asked which screening test was performed. In the 71 HIV-infected children for which we obtained an answer, no child was known for PAH. However, only two had been screened for PAH, and the diagnosis was not confirmed. In conclusion, PAH in HIV-infected children is possibly underestimated due to lack of screening. Systematic echocardiographic evaluation should be performed in HIV-infected children.
 
The L–R pattering is caused at the node by an early breaking of bilateral symmetry. The nodal gene is essential in this function and the midline acts as a physical and molecular barrier to determine correct side-specific gene expression. The leftward Nodal flow (arrow) transport to the left wall of the node the nodal vesicular parcels. At this level Nodal interplays with other signalings including Notch, LeftyA, Cryptic, Pitx2, etc. (Modified from Zhu et al 2006; 14:14–25)
A) Anatomical aspect of normal heart with situs solitus. Note the right-handed spiral pattern of outflow tract and great arteries. (B) Right-handed shell of the snail Amphidromus perversus rufocinctus.
Transposition of great arteries (TGA) is one of the most common and severe congenital heart diseases (CHD). It is also one of the most mysterious CHD because it has no precedent in phylogenetic and ontogenetic development, it does not represent an alternative physiological model of blood circulation and its etiology and morphogenesis are still largely unknown. However, recent epidemiologic, experimental, and genetic data suggest new insights into the pathogenesis. TGA is very rarely associated with the most frequent genetic syndromes, such as Turner, Noonan, Williams or Marfan syndromes, and in Down syndrome, it is virtually absent. The only genetic syndrome with a strong relation with TGA is Heterotaxy. In lateralization defects TGA is frequently associated with asplenia syndrome. Moreover, TGA is rather frequent in cases of isolated dextrocardia with situs solitus, showing link with defect of visceral situs. Nowadays, the most reliable method to induce TGA consists in treating pregnant mice with retinoic acid or with retinoic acid inhibitors. Following such treatment not only cases of TGA with d-ventricular loop have been registered, but also some cases of congenitally corrected transposition of great arteries (CCTGA). In another experiment, the embryos of mice treated with retinoic acid in day 6.5 presented Heterotaxy, suggesting a relationship among these morphologically different CHD. In humans, some families, beside TGA cases, present first-degree relatives with CCTGA. This data suggest that monogenic inheritance with a variable phenotypic expression could explain the familial aggregation of TGA and CCTGA. In some of these families we previously found multiple mutations in laterality genes including Nodal and ZIC3, confirming a pathogenetic relation between TGA and Heterotaxy. These overall data suggest to include TGA in the pathogenetic group of laterality defects instead of conotruncal abnormalities due to ectomesenchymal tissue migration.
 
| Characteristics of South Asian immigrant studies. 
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract associated with significant morbidity. While IBD occurs in genetically susceptible individuals, the etiology is multifactorial, involving environmental influences, intestinal dysbiosis, and altered immune responses. The rising incidence of IBD in industrialized countries and the emergence of IBD in countries with traditionally low prevalence underscore the importance of environmental influences in the pathobiology of the disease. Moreover the high incidence of IBD observed in the South Asian immigrant population in the United Kingdom and Canada further supports the influence of environmental factors.
 
Chest radiograph on admission showing right-sided changes.
Repeat chest radiograph 1 day after admission demonstrating resolution of the changes within 24 h.
Post-aspiration chest x-ray showing well-defined radio-dense opacities through all zones of the right lung and similar but less extensive changes on the right.
Tracheoesophageal cleft with nasojejunal tube visible in the esophagus. Note the absence of a “fistula” or “tube connection” but a confluence of the tracheal and esophageal lumens.
We describe a case of bilateral inhalation of barium in an infant following a barium swallow for investigation of dusky spells associated with feeds. A bronchoscopy subsequently revealed the presence of a mid-tracheal tracheo-esophageal cleft. To date, little has been reported on barium aspiration in children and there is no consensus for management. We review the literature on barium aspiration, its consequences, and make recommendations for management. © 2014 Jackson, Kapur, Goyal, Choo, Sarikwal, Masters and Isles.
 
Background: It is well established that people with intellectual disabilities are at higher risk of developing mental illnesses. This study aimed to assess the need for a specialized service for people (children and adults) with intellectual disabilities and mental health problems living in Israel. Methods: Our research question was: is there a need for a specialist mental health service for people with intellectual disabilities living in Israel and, if so, what type of service would be most appropriate? We conducted a qualitative study using semi-structured interviews with 14 major stakeholders to identify key themes in response to our research question. The data were coded and themes were identified. Results: Participants were generally not satisfied with current mental health care for people with intellectual disabilities and there was a general agreement that services are in need of improvement. We identified three major themes from the data. These were: current services, future services, and ways to facilitate change. Conclusion: We hope that our findings will be instrumental in shaping the ongoing debate about the best form of delivery of services to this population in Israel. Specifically, we suggest the development of a more specialized system, with the formation of multidisciplinary regional assessment and treatment units in parallel with improved relevant training for all mental health workers and the possibility of referral to specialized teams in more complex cases.
 
Surgical correction of tetralogy of Fallot is still one of the most frequently performed intervention in pediatric cardiac surgery, and in many cases, it is far from being a complete and definitive correction. It is rather an excellent palliation that solves the problem of cyanosis, but predisposes the patients to medical and surgical complications during follow-up. The decision-making process regarding the treatment of late sequel is among the most discussed topics in adult congenital cardiology. In post-operative Fallot patients, echocardiography is used as the first method of diagnostic imaging and currently allows both a qualitative observation of the anatomical alterations and a detailed quantification of right ventricular volumes and function, of the right ventricular outflow tract, and of the pulmonary valve and pulmonary arteries. The literature introduced many quantitative echocardiographic criteria useful for the understanding of the pathophysiological mechanisms involving the right ventricle and those have made much more objective any decision-making processes.
 
| A brief overview of the use of genetic testing in the US and France.
| Sample characteristics. France, N (%) US, N (%) p GENDER OF THE RESPONDERS
Changes in age of ASD diagnosis in France during the last 40 years [extracted from Ref. (46); courtesy of Claude Bursztejn]. *The dot line indicates that the 2001–2005 result should be regarded with caution as based on only N = 19 cases.
Background: There are many societal and cultural differences between healthcare systems and the use of genetic testing in the US and France. These differences may affect the diagnostic process for autism spectrum disorder (ASD) in each country and influence parental opinions regarding the use of genetic screening tools for ASD. Methods: Using an internet-based tool, a survey of parents with at least one child with ASD was conducted. A total of 162 participants from the US completed an English version of the survey and 469 participants from France completed a French version of the survey. Respondents were mainly females (90%) and biological parents (94.3% in the US and 97.2% in France). Results: The mean age of ASD diagnosis reported was not significantly different between France (57.5 ± 38.4 months) and the US (56.5 ± 52.7 months) (p = 0.82) despite significant difference in the average age at which a difference in development was first suspected [29.7 months (±28.4) vs. 21.4 months (±18.1), respectively, p = 7 × 10−4]. Only 27.8% of US participants indicated that their child diagnosed with ASD had undergone diagnostic genetic testing, whereas 61.7% of the French participants indicated this was the case (p = 2.7 × 10−12). In both countries, the majority of respondents (69.3% and 80% from France and the US, respectively) indicated high interest in the use of a genetic screening test for autism. Conclusion: Parents from France and the US report a persistent delay between the initial suspicion of a difference in development and the diagnosis of ASD. Significantly fewer US participants underwent genetic testing although this result should be regarded as exploratory given the limitations. The significance of these between country differences will be discussed.
 
| Follow-up period and percentage of lost to follow-up in randomly selected recent retrospective case series from 2013 (as sorted in 
| Recent hypospadias assessment tools and their pros and cons. 
| Follow-up parameters after hypospadias surgery. 
Hypospadias is a challenging field of urogenital reconstructive surgery with different techniques being currently used. Modern surgery claims that it is possible to create a functionally and cosmetically normal penis. Continuous re-evaluation and assessment of outcome may have a major impact on future clinical practice. Assessment of outcome includes: complication rate, cosmetic appearance of the penis, functional outcome (micturition, sexuality), and psychological factors such as quality of life and psychosexual life. This article briefly reviews current strategies of outcome assessment. Somehow in the future, we will be able to give an accurate estimation of the long-term consequences of being born with hypospadias.
 
| Food use by age group. 
| Association of six types of foods with infant health, age < 6 months. 
| Association of six types of foods with infant health, age 6 months to 1 year. 
The health benefits of exclusive breastfeeding are well-known, but the relative detrimental impacts of other foods on infant health are unknown. Because infants in developing countries are fed a wide range of food, quantifying the burden of these diverse feeding practices on infant health is essential for public health policy. We used data from the Demographic Health Survey from 20 developing countries over multiple years to examine the independent association of six different types of food (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods) with five measures of infant health (length, weight, diarrhea, fever, and cough). We estimated associations with regression analysis, controlling for confounding factors with infant, mother, and household factors and community-year fixed effects. We used these estimates in a simulation model to quantify the burden of different combinations of food on infant health. We show that for an infant younger than 6 months old, following current guidelines and exclusively breastfeeding instead of giving the infant solid foods may increase length by 0.75 cm and weight by 0.25 kg and decrease diarrhea, fever, and cough prevalence by 8, 12, and 11%, respectively. We found that the burden on infant health of some feeding practices is less than others. Although all other feeding practices are associated with worse health outcomes than exclusive breastfeeding, breastfeeding supplemented with liquids has a lower burden on infant health than solid foods and infant formula has a lower burden than milk or non-milk liquids as measured by four of five health metrics. Providing specific quantified burden estimates of these practices can help inform public health policy related to infant feeding practices.
 
Esophageal atresia with or without tracheoesophageal fistula (EA ± TEF) occurs in 1 out of every 3000 births. Current survival approaches 95%, and research is therefore focused on morbidity and health-related quality of life issues. Up to 50% of neonates with EA ± TEF have one or more additional malformations including those of the respiratory tract that occur in a relatively high proportion of them and particularly of those with vertebral, anal, cardiac, tracheoesophageal, renal, and limb association. Additionally, a significant proportion of survivors suffer abnormal pulmonary function and chronic respiratory tract disease. The present review summarizes the current knowledge about the nature of these symptoms in patients treated for EA ± TEF, and explores the hypothesis that disturbed development and maturation of the respiratory tract could contribute to their pathogenesis.
 
Bladder augmentation was first described in 1899. The goal at the time was to establish the ideal method to create a simple capacious reservoir for the safe storage of urine. That simple idea has over the last 100 years grown into one of the most dynamic areas in Pediatric Urology. Creative minds and hands from individuals in multiple disciplines have led us from creating a reservoir to the threshold of recreating a functional organ. In this review, we look at the historical evolution of bladder augmentation and how it exponentially grew in scope from those initial descriptions of intestinocystoplasty to the work being reported today in the field of tissue engineering.
 
| Demographic characteristics of transplanted children with an AC and transplanted controls.
Graft survival curves for children with AC prior to transplantation compared to those transplanted without AC.
Objective: Studies evaluating renal transplant (RT) outcome in children who underwent an augmentation cystoplasty (AC) are contradictory and the current knowledge is based on studies with a limited number of patients. The aim of this study is to compare RT outcome between children who underwent AC and those without augmentation. Patients and methods: A total of 20p who underwent an AC prior to the RT (12 with ureter and 8 with intestine) were enrolled in the study and were compared to a control group of 24p without AC, transplanted in the same time period (1991-2011). Data including; age at transplant, allograft source, urological complications, urinary tract infections (UTI) incidence, the presence of VUR, and patient and graft survival were compared between the groups. Results: Mean age at RT and mean follow-up were 9.7 vs. 7.9 years and 6.9 vs. 7.9 years in the AC group and control group, respectively (NS). The graft originated in living donors for 60% of AC patients and 41.6% of the control RT patients. The rate of UTI were 0.01 UTI/patient/year and 0.004 UTI/patient/year in the augmented group and controls, respectively (p = 0.0001). In the AC group of 14p with UTIs, 10 (71%) had VUR and 5p out of 8 (62.5%) in the control group had VUR. In the AC group, of the 7p with ≥3 UTIs, 3 (43%) were non-compliant with CIC and the incidence of UTIs was not related with the type of AC or if the patient did CIC through a Mitrofanoff conduit or through the urethra. Graft function at the end of study was 92.9 ± 36.85 ml/min/m(2) in the AC group and 88.17 ± 28.2 ml/min/m(2) in the control group (NS). Graft survival at 10 years was also similar 88% in the AC group and 84.8% in controls. In the AC group 3p lost their grafts and 5 in the control group with respective mean follow-up of 10.6 ± 4.3 and 7.1 + 4.7 years. Conclusion: There are no significant differences in the RT outcome between children transplanted with AC or without. However, recurrent UTIs are more frequent in the former group and these UTIs are related with non-compliance with CIC or the presence of VUR but, even so, UTIs will not lead to impaired graft function in most of the patients.
 
Flow chart of the inclusion of pregnancies in the study.
The association between increasing maternal BMI and BW z-score in babies of GDM and non-GDM women, adjusted for all confounding factors. Interaction GDM × maternal BMI (p < 0.001). GDM , non-GDM .
The association between increasing maternal BMI and the mean differences between BW and BL z-scores in GDM and non-GDM women. Interaction GDM × maternal BMI (p < 0.01). GDM , non-GDM .
Objective: To investigate the effect of the interaction between gestational diabetes mellitus (GDM) and maternal body mass index (BMI) on the individual neonatal growth parameters. Design: Retrospective cohort study. Setting: A tertiary maternity service in Sydney, Australia, between 2005 and 2009. Population: A cohort of 8859 women. Methods: Generalized linear models. Main outcome measures: Neonatal growth parameters, represented by z-scores for infant birth weight (BW), birth length (BL), and head circumference (HC) in GDM and non-GDM groups. Results: Only GDM alone had an independent and positive effect on BL (p = 0.02) but not on BW or HC. In addition, in pregnancies complicated with GDM, the association between maternal weight and BW was significantly stronger (p < 0.001). In combination, GDM and maternal BMI significantly affected z-score differences between BW and BL (p < 0.001), in that underweight mothers had babies that were lighter relative to their length and inversely obese mothers had babies that were heavier relative to their length. Conclusion: GDM independently influences BL and increases the association between maternal BMI and BW. In accordance with the hypothesis of the fetal origins of health and disease, the pronounced effects of GDM on fetal growth patterns demonstrated in this study are likely to influence long-term health outcomes in children.
 
A simplified diagram on the development of severe lung disease in adulthood (blue) and the possible factors (yellow) that likely influence the progression of disease. COPD, chronic obstructive pulmonary disease; CSLD, chronic suppurative lung disease; ETS, environmental tobacco smoke exposure.
Addressing health issues in childhood is needed to reduce the long-term impairment and social disadvantage in adults. This paradigm is striking for lung health for many reasons, including the impact of respiratory infections and environmental insults upon post-natal lung development, which increase the risk of future lung disease, such as COPD and bronchiectasis. We have briefly presented our framework for the development of severe COPD and/or bronchiectasis (Figure (Figure1)1) and our model of research and care. In our second annual workshop, we also highlighted several questions concerning the airway microbiome and related host responses in children with CSLD/bronchiectasis. Through our CRE, we have built partnerships with Indigenous leaders, scientists, and clinicians working toward a common goal of reducing disparity though high-quality science and care. While we are beginning to improve lung health in Indigenous children through several projects addressing various clinically feasible interventions, much work is still to be done in reducing disparity in lung health between Indigenous and non-Indigenous Australian and NZ peoples.
 
Top-cited authors
Shyamali Chandrika Dharmage
  • University of Melbourne
Adnan Custovic
  • Imperial College London
Clair-Yves Boquien
  • French National Institute for Agriculture, Food, and Environment (INRAE)
Arjan B Te Pas
  • Leiden University Medical Centre
Aleksandra Wesolowska
  • Medical University of Warsaw