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Childhood adversity has been associated with hypothalamic-pituitary-adrenal axis dysregulation, which is associated with mental and physical health consequences. However, associations between childhood adversity and cortisol regulation in the current literature vary in magnitude and direction. This multilevel meta-analysis examines the association between childhood adversity and diurnal cortisol measures, as well as potential moderators of these effects (adversity timing and type, study or sample characteristics). A search was conducted in online databases PsycINFO and PubMed for papers written in English. After screening for exclusion criteria (papers examining animals, pregnant women, people receiving hormonal treatment, people with endocrine disorders, cortisol before age 2 months, or cortisol after an intervention), 303 papers were identified for inclusion. In total, 441 effect sizes were extracted from 156 manuscripts representing 104 studies. A significant overall effect was found between childhood adversity and bedtime cortisol, r = 0.047, 95% CI [0.005, 0.089], t = 2.231, p = 0.028. All other overall and moderation effects were not significant. The lack of overall effects may reflect the importance of the timing and nature of childhood adversity to adversity's impact on cortisol regulation. Thus, we offer concrete recommendations for testing theoretical models linking early adversity and stress physiology.

Objective: Attachment theory suggests that parent responsiveness to infant distress predicts secure parent-child attachment and subsequent healthy child development. While much is known about microsystem factors that interfere with responsive caregiving, there is a paucity of research investigating how exosystem factors, such as neighborhood crime, affect parenting., Method: In a sample of 200 diverse caregivers and their 5- to 21-month-old infants ( M = 11.82; 49% male), we leveraged data from a randomized clinical trial of Attachment and Biobehavioral Catch-up (ABC), an attachment-based intervention, to assess whether individual level burden (indicated by single-parent status, low income, residential instability, young parenthood, parental psychopathology, and own history of early adversity) and neighborhood crime density (geocoded within a 500 ft radius of parent's residence) were associated with their beliefs about infant crying, an indicator of responsive parenting., Results: Consistent with Bronfenbrenner's ecological systems' theory of development, both greater exposure to individual burden indicators and greater neighborhood crime density predicted greater maladaptive beliefs about infant crying, suggesting that contextual factors outside the household are associated with parenting cognitions. Further, when accounting for the effect of crime and individual burden on parental beliefs about infant crying, participation in the ABC intervention was effective in reducing maladaptive parenting beliefs., Conclusions: We consider implications for multi-level intervention approaches that target family processes, neighborhood-level factors, and policy initiatives to promote community wellbeing and positive child development.

Attachment and Biobehavioral Catch-up (ABC) demonstrates efficacy in improving parent and child outcomes, with preliminary evidence for effectiveness in community settings. The objective of this study was to assess the effectiveness of a community-based ABC implementation in improving parent outcomes as well as to examine potential mediators and moderators of intervention effectiveness. Two hundred parents and their 5- to 21-month-old infants recruited from an urban community were randomly assigned to receive ABC or be placed on a waitlist. The majority of participants had a minority racial or ethnic background. Before intervention, parents completed questionnaires about sociodemographic risk and adverse childhood experiences. At both baseline and follow-up, parents reported depression symptoms and were video-recorded interacting with their infant, which was coded for sensitivity. The ABC intervention predicted significant increases in parental sensitivity and, among parents who completed the intervention, significant decreases in depression symptoms. Changes in parental depression symptoms did not significantly mediate the intervention effects on sensitivity. Risk variables did not moderate the intervention effects. The results indicate that ABC shows promise for improving parent outcomes in community settings, supporting dissemination.

Everyday language use, including the pronouns people choose when speaking to romantic partners, may reflect underlying aspects of relationship functioning and may have important implications for understanding couple conflict and dating aggression more generally. The current study measured couples' hour-to-hour "we," "I," and "you" speech in daily life and examined symmetry in pronoun use, or the extent to which partners mirror each other in the frequency of the pronouns they use. First, we examined associations between symmetry in pronoun use and overall levels of dating aggression. Second, we investigated whether aggressive couples evidence patterns of pronoun use distinct from nonaggressive couples when they become annoyed with each other. Multilevel models showed that symmetry in "we" speech and symmetry in "I" speech each were related to lower levels of dating aggression. In addition, symmetry in couples' "you" speech increased during hours of annoyance, but only among those couples reporting high levels of aggression in their relationships. These results demonstrate how everyday language use relates to couples' general tendencies toward aggression and how such patterns are linked to ongoing fluctuations in the emotional tone of the relationship. The discussion focuses on implications for intervention and the use of novel ambulatory assessment methods for capturing couple processes in real-life contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dysregulation of diurnal cortisol rhythms is often seen among children exposed to early adversity and has been associated with a variety of negative physical and mental health outcomes. The present study examined whether two indicators of deprivation, sociodemographic burden and observed parental insensitivity, were associated with child diurnal cortisol rhythms among a diverse community sample of 250 infants ages 5 to 22 months (M = 12.68 months, 47.2% male). The sample was diverse in terms of socioeconomic status as assessed by household income (M = $59,163, SD = $57,775, range = $0-230,000) and infant race/ethnicity (41.6% African American, 19.2% White, 17.2% multiracial, 14.0% Hispanic/Latin, 2.8% Caribbean, 2.8% other, 1.2% American Indian/Alaska Native, and 1.2% Asian). Sociodemographic burden indicators were assessed through questionnaires completed by the parent. Parental sensitivity was assessed through observations of parents' interactions with their infants during a play interaction task. Cortisol was assayed from infant saliva samples collected at waking and bedtime across 3 days. Structural equation modeling revealed that higher sociodemographic burden, but not parental insensitivity, was associated with blunted diurnal cortisol slopes. Neither sociodemographic burden nor parental insensitivity were associated with the cortisol awakening response. These findings suggest that sociodemographic burden may be an important early predictor of diurnal cortisol slope dysregulation, highlighting the importance of interventions providing support to individuals who experience sociodemographic burden and promoting reduction of these early stressors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Numerous event-related potential (ERP) studies have examined adults' neural responses to child emotional expressions to understand the neurobiological mechanisms contributing to caregiving. It is unclear, however, whether one emotion evokes an enhanced response across components, and whether this pattern differs based on parent status or other sample characteristics. This meta-analysis quantified adult responses to child emotional expressions at the N170 and the late positive potential (LPP) components. Cohen's d reflected the difference between crying and neutral (CN), crying and laughing (CL), and laughing and neutral (LN) N170 and LPP amplitudes. Crying expressions elicited slightly enhanced N170 and LPP amplitudes relative to neutral and laughing expressions (N170 CN: k = 24, d = -0.09, p < 0.001; N170 CL: k = 30, d = -0.07, p = .004; LPP CN: k = 20, d = 0.12, p = .027; LPP CL: k = 27, d = 0.10, p < .001), and laughing expressions elicited slightly enhanced N170 amplitudes relative to neutral expressions (N170 LN : k = 21, d = -0.05, p = .02). Parental status, child age, risk factors for insensitive caregiving, and measurement characteristics moderated some effect sizes, with reference electrode emerging as the most consistent moderator. Results shed light on the typical pattern of neural response to child emotions and characteristics that may moderate this response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Frequently, general pediatricians could face a patient with syncope, which represents approximately 1% to 3% of emergency visits. Micturition syncope is a transient loss of consciousness with onset immediately before, during, or after micturition. Literature evidence indicates that healthy young men are a population with major risk for presenting micturition syncope, with a peak of incidence around 40 to 50 years of age. Usually, this syncope occurs in the morning, after wake-up, or, more generally, when the male patients assume the orthostatic position after a period of supine position in a warm bed. No information on micturition syncope clinical presentation and prevalence in childhood is available in the literature, and probably, this kind of syncope is unrecognized in childhood. We describe 4 unreported pediatric patients with a diagnosis of micturition syncope and well-defined clinical presentation. In all patients, the syncope has been presented in the same conditions: in the morning; after wake-up; in an orthostatic position; just before, after, or during urinary bladder voiding; and with spontaneous recovery in few minutes. Interestingly, 1 patient presented with the syncope during urinary bladder voiding by autocatheterization. In our patients, all investigations made as the first approach in the pediatric emergency department did not show any abnormal results, possibly underlying the syncope episodes. By describing our experience, we want to underline the clinical presentation of micturition syncope and give to the clinicians the elements to recognize and manage it easily in children.

This study examined nonverbal intelligence and scholastic achievement in children with type 1 diabetes. In a retrospective case-control study, 69 children (35 males) ages 5-10 years with type 1 diabetes and 69 healthy controls matched to patients by age, gender and socioeconomic status were compared according to their performance on Raven's Coloured Progressive Matrices and their scholastic grades. No differences in nonverbal intelligence and grades were observed between children with type 1 diabetes and healthy control subjects. Raven's Coloured Progressive Matrices scores inversely correlated with duration of illness both in children with early onset of type 1 diabetes and poor metabolic control. Possible explanations of the results and implications are discussed.

With worries and risky behaviors becoming more prominent in adolescence, this study investigated bidirectional temporal connections between these two important adolescent concerns, that is, whether change in one concern is linked to change in the other either within the same day or during the next day. We also tested whether the coping strategy of seeking support from family and friends moderated the link between worries and risky behaviors. For 10 days, an ethnically and racially diverse sample of adolescents (N = 103; M age = 18.0) reported on 26 common worries, 18 risky behaviors, and the impact of seeking support from others. Multilevel models showed that worries and risky behaviors covaried on the same day and that worries predicted next-day risky behavior for male but not female participants. In contrast, risky behaviors did not predict next-day worries. For adolescents reporting negative experiences of support seeking, worries led to next-day risky behaviors and risky behaviors led to next-day worries. Female adolescents' positive support-seeking experiences buffered the association between risky behaviors and next-day worries. These results were significant beyond any influence of daily negative mood or depressive and anxiety symptoms. The data demonstrate that worries and risky behaviors may be situational triggers for each other and highlight the importance, from intervention perspectives, of adolescents' communication of concerns to others.

Background: Basal levels of androgens, in particular 17-hydroxyprogesterone (17OHP), are widely debated as predictors of non-classical congenital adrenal hyperplasia (NCCAH) among patients with precocious pubarche (PP). Many authors have recommended the use of adrenocorticotropic hormone (ACTH) stimulation test in children with PP. The aim of our study was to identify clinical and biochemical predictors of NCCAH in children with PP., Methods: We conducted a prospective study of 92 patients with PP undergoing an ACTH stimulation test. We tested the association of basal clinical and biochemical parameters with NCCAH diagnosis. Patients were suspected to have NCCAH if their stimulated 17OHP plasma levels were >10 ng/mL. In these patients, the diagnosis was confirmed by genetic test., Results: Seven (7.6%) patients resulted having NCCAH. The best basal biochemical predictor for NCCAH was 17OHP level >2 ng/mL. In fact, a basal 17OHP level >2 ng/mL had 100% (95% confidence interval (CI), 59.04-100) sensitivity and 93% (95% CI, 85.3-97.37) specificity. The area under the receiver-operating characteristic curve for 17OHP was 0.99 (95% CI, 0.98-1.007)., Conclusions: Basal 17OHP cut-off of 2 ng/mL was very effective in predicting NCCAH among our patients with PP. Assay-specific cut-off would probably be the best strategy to avoid unnecessary ACTH test.

Objectives: Existing studies usually do not measure the free vitamin D in pediatric patients with inflammatory bowel disease (IBD) and not consider the effect of inflammation on vitamin D levels. The aim of our study was to evaluate the concentrations of vitamin D-binding protein (VDBP), total and free 25-hydroxyvitamin-D (25(OH)D), and to correlate these values with the disease activity markers., Methods: Newly diagnosed children with IBD and a group of healthy controls (HCs) were enrolled. VDBP and total and free 25(OH)D levels were measured by enzyme-linked immunosorbent assay and compared using the Student t test. In each patient with IBD, the activity scores of disease and the main inflammation markers were correlated to total and free 25(OH)D levels. C-reactive protein was also measured in the control group, and it was related to VDBP by a linear regression test for all the groups., Results: Fifty-one consecutive children were enrolled: IBD = 33, HC = 18. Levels of total 25(OH)D were higher in HC than in patients with IBD (P = 0.01). The free/total 25(OH)D ratio was, however, higher in patients with IBD compared to HC (P < 0.001). Finally, levels of VDBP were lower in patients with IBD than in HC (P = 0.001). A significant direct correlation was found between the free/total 25(OH)D ratio and the activity index of disease (r: 0.17; P = 0.01). Moreover, in patients with IBD and controls we found a significant indirect correlation between VDBP and C-reactive protein (r: 0.12; P = 0.01)., Conclusions: Inflammation inversely correlates to VDBP concentrations and patients with IBD, despite their deficiency in total 25(OH)D, have normal or even higher levels of free 25(OH)D.

Objective: We aimed to investigate which clinical and metabolic factors could influence the estimated glomerular filtration rate (eGFR) levels, evaluating a large population of obese children without suspect of primary kidney disease., Design: Retrospective, cross-sectional study., Setting: Pediatric university department., Subjects: We enrolled 2,957 obese children and adolescents consecutively attending our department between January 2000 and 2017. Inclusion criteria were body mass index (BMI) > 95th percentile and eGFR > 90 mL/min/1.73 m 2 . Exclusion criteria were secondary forms of obesity, eGFR < 90 mL/min/1.73 m 2 , proteinuria/hematuria at urine dipstick, or consumption of any medication., Interventions: Weight, waist circumference, height, waist to height ratio (W/Hr), BMI-standard deviation score (SDS), pubertal stage, systolic blood pressure (SBP) and diastolic blood pressure (DBP), duration of obesity, insulin, eGFR, and homeostasis model assessment (HOMA-IR) were obtained. A general linear model was performed for a multiple variable analysis., Main Outcome Measure: The population was divided in tertiles for BMI-SDS, W/Hr, SBP- and DBP-SDS, HOMA-IR, and duration of obesity. We compared eGFR levels among these tertiles., Results: The eGFR levels significantly increased across both BMI-SDS and W/Hr tertiles. Conversely the eGFR levels significantly decreased across SBP-SDS, HOMA-IR, and duration of obesity tertiles. No significant differences in eGFR levels across DBP-SDS tertiles were detected. Pubertal patients presented significantly lower eGFR values compared with prepubertal patients. A general linear model for eGFR variance including as covariates W/Hr, HOMA-IR, duration of obesity, pubertal stage, BMI-SDS, and SBP-SDS (model R 2 39.7%; model P < .00001) was performed. It confirmed a direct association of eGFR values with BMI-SDS and an indirect association with HOMA-IR, duration of obesity, pubertal stage, and SBP-SDS., Conclusions: We showed a positive correlation of eGFR with both BMI-SDS and a negative one with SBP-SDS, HOMA-IR, pubertal stage, and duration of obesity. The duration of obesity was the variable most significantly associated to eGFR levels., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

Objectives: The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course., Methods: This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected., Results: One hundred eleven patients were enrolled. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%)., Conclusion: Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports.

Objective: To examine changes over a five-year period in body image accuracy and dissatisfaction, as well as relationships with disordered eating behaviors (DEBs), in young patients with type 1 diabetes., Methods: Of 81 children (42 male, 39 female) with type 1 diabetes first assessed at ages 5.1-10.06 years, 67 (83%) were re-enrolled and interviewed as adolescents (aged 10.07-15.08 years) at follow-up. DEBs were assessed using a parent-report standardized measure. Height and weight were determined, and BMI was calculated. Glycemic control was assessed by glycated hemoglobin., Results: BMI increased from childhood to adolescence. The general tendency towards body size underestimation (i.e., perceiving the body to be smaller than it is) and dissatisfaction, already described at baseline, was found unchanged at follow-up, revealing continuing attitude towards body image problems. Body-size perception accuracy, degree of body-size dissatisfaction, and HbA1c did not increase significantly over five years, but the presence of DEBs was observed. Degree of body dissatisfaction was found to be a significant predictor for DEBs (standardized beta = 0.272, p < 0.05)., Conclusion: Body image problems persisted over the five-year study period and were found associated with higher levels of DEBs. Identification of such body image characteristics may be useful in developing strategies for intervention early in the course of illness., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Since standardization of the ICCS terminology, only two small case series of children with extraordinary daytime only urinary frequency (EDOUF) have been published. The aims of the present study were i) to describe a large cohort of children affected by EDOUF, to evaluate its rate among the main micturition pediatric disturbances, and to determine if there is different EDOUF onset among seasons; ii) to investigate possible associations with urodynamic abnormalities by non-invasive techniques; iii) to evaluate whether postponing micturition exercise (PME) can objectively verify the anamnestic data hinting at the EDOUF diagnosis; and iv) to determine the effect of postponing micturition at home., Material and Methods: We reviewed the records of all patients with EDOUF, nocturnal enuresis, and/or overactive bladder firstly examined from March 2012 to February 2016. We evaluated post-void residual and bladder wall thickness by urinary ultrasound and uroflowmetry and recorded the season in which the EDOUF started. Through the PME, the EDOUF diagnosis was confirmed if patients were able to postpone micturition reaching at least 80% of the expected bladder capacity without showing urinary incontinence. At home, we recommended postponing micturition for a maximum of 3 h if EDOUF affected the normal daily activities of both children and parents. We set a telephone interview for 3 months later., Results: The clinical characteristics of the EDOUF population are shown in the Table. The EDOUF rate was 12.1%. The rate of EDOUF onset was significantly lower during the summer than in other seasons (p = 0.02) and the OR for onset of EDOUF in the summer - compared with the other seasons - was 0.37 (95% CI 0.18-0.74; p = 0.005). Eighty-five (80.2%) patients reported an intermittent trend of the EDOUF with variable periods of improvement and worsening. All the EDOUF patients had normal uroflowmetry, 1/106 had post-micturition bladder wall thickness >5 mm and one post-void residual. At the PME, 106 out of 106 (100%) patients with EDOUF were able to reach at least 80% of the EBC without showing urinary incontinence or urgency incontinence. After 3 months, in 98.1% of the patients the symptoms had disappeared or improved., Discussion and Conclusions: Childhood EDOUF is rather common and is generally associated with normal non-invasive urodynamic patterns. The PME allows verification of anamnestic data of EDOUF. The sole recommendation to postpone micturition for a maximum of 3 h or until the micturition postponement became stressful could be considered as a possible approach., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Recently, mutations of makorin RING-finger protein 3 (MKRN3) have been described in familial central precocious puberty. Serum levels of this protein decline before the pubertal onset in healthy girls and boys. The aim of the study is to investigate MKRN3 circulating levels in patients with central precocious puberty., Methods: We performed an observational cross-sectional study. We enrolled 17 patients with central precocious puberty aged 7 years (range: 2-8 years) and breast development onset <8 years; 17 prepubertal control age-matched patients aged 6.3 years (2-8.2); and 10 pubertal stage-matched control patients aged 11.4 years (9-14). Serum values of MKRN3, gonadotropins, (17)estradiol and Anti-Müllerian Hormone were evaluated and the MKRN3 genotyped in central precocious puberty patients., Results: No MKRN3 mutation was found among central precocious puberty patients. MKRN3 levels were lower in patients with central precocious puberty compared to prepubertal age-matched ones (p: 0.0004) and comparable to those matched for pubertal stage. MKRN3 levels were inversely correlated to Body Mass Index Standard Deviations (r:-0.35; p:0.02), Luteinizing Hormone (r:-0.35; p:0.03), FSH (r:-0.37; p:0.02), and (17)estradiol (r: -0.36; p:0.02)., Conclusions: We showed that girls with central precocious puberty had lower peripheral levels of MKRN3 compared to age-matched pairs and that they negatively correlated to gonadotropins, estrogen, and BMI. Our findings support the MKRN3 involvement in central precocious puberty also in absence of deleterious mutations, although our sample size is small. In addition our data suggest the role of MKRN3 in the complex mechanism controlling puberty onset and its interaction with other factors affecting puberty such as nutrition.

Purpose: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury., Materials and Methods: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated., Results: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p <0.001), respectively. Of congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney resulted in significant risk factors for renal injury (HR 8.75, 95% CI 2.77-27.65)., Conclusions: In an evaluation of a large cohort of patients enrolled early with congenital solitary functioning kidney with a prenatal diagnosis, excluding those with neonatal onset of renal damage, the prevalence of renal damage was 3.9%. Among congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney represented the major risk factor., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Bisphenol A (BPA) exposure has been associated with increased incidence of diabetes and obesity in adults., Objectives: To evaluate whether an association between BPA urinary levels and insulin resistance as well as adiponectin and resistin production and serum concentrations may occur in obese children., Methods: Clinical and biochemical features of 141 obese children were collected. Serum resistin and adiponectin were evaluated. Insulin resistance and urinary BPA levels were assessed. Moreover, the effect of BPA on adiponectin and resistin gene expression in adipocytes from eight normal weight prepubertal children was investigated by quantitative real-time RT-PCR (qPCR)., Results: Direct association between BPA and homeostasis model assessment (r = 0.23; p: 0.0069) and a strong inverse association between BPA and adiponectin have been found (r = -0.48; p < 0.0001). In adipocytes, resistin expression was detected only after BPA treatment, while adiponectin expression resulted down-regulated after BPA exposure (p < 0.05 at both 10 and 100 nM BPA concentrations)., Conclusions: We suggest the involvement of BPA in the development of insulin resistance in childhood obesity highlighting that urinary BPA levels are directly associated with insulin resistance regardless of BMI. This association may be explained, at least partly, by the findings that BPA affects resistin and adiponectin production in adipose tissue cultures., (© 2016 World Obesity Federation.)

Background: The N-acetyltransferase 2 ( NAT2 ) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin-resistance-related traits., Objective: Evaluate the association of this polymorphism with anthropometric and metabolic parameters in obese children and adolescents., Subjects: A total of 748 obese children and adolescents were enrolled., Methods: Anthropometric and laboratory data were collected. During oral glucose tolerance test, the presence of a possible exaggerated plasma glucose excursion at 1 h (1HPG) or impaired glucose tolerance (IGT) was considered. Homeostasis model assessment, oral disposition index (oDI) and insulinogenic index (IDI) were calculated. Patients were genotyped for the NAT2 A803G polymorphism., Results: The prevalence of both IGT and elevated-1HPG was higher in children carrying the A803 allele (P = .02 and P = .03). Moreover, this allele was associated with both oDI and IGI reduction (P = .01). No differences among the NAT2 A803G genotypes for the other parameters were shown. Children homozygous for the A allele presented an odds ratio (OR), to show IGT of 4.9 (P = .01). Children both homozygous and heterozygous for the A allele had higher risk to show elevated-1HPG (OR of 2.7, P = .005; and OR = 2.3, P = .005) compared with patients homozygous for the NAT2 803G allele., Conclusions: NAT2 A803 allele seems to play a role in worsening the destiny of obese children carrying it, predisposing them to elevated-1HPG and IGT and then to a possible future type 2 diabetes mellitus throughout an impairment of pancreatic β-cellular insulin secretion as suggested by oDI and IGI reduction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Increased thyroid stimulating hormone (TSH) serum concentration can be a marker of subclinical hypothyroidism (SCH) or transient hyperthyrotropinemia. The aim of our study was to evaluate whether high serum TSH concentrations in allergic children could represent true SCH or isolated and transient hyperthyrotropinemia., Methods: We enrolled 620 allergic children (1.11-12.8 years) consecutively attending to our department. They were classified as atopics and non-atopics on the basis of the atopy work-up and, at baseline, they were investigated for thyroid function and low-grade inflammation state. Further, TSH was evaluated after 6 (T1) and 12 (T2) months., Results: Both atopics and non-atopics showed higher SCH prevalence compared to controls (p=0.0055 and p=0.02, respectively), and a significant association between atopy and SCH (OR 10.11, 95% CI 1.36-75.12) was found. Both at T1 and T2, atopics had a significant risk of developing severe SCH compared to non-atopics (RR 1.8, 95% CI 1.39-2.34 and 1.61, 95% CI 1.21-2.14; respectively)., Conclusions: Our data may suggest that hyperthyrotropinemia in atopic children could be used as a marker of true SCH.

Adiponectin (Acrp30), its high molecular weight (HMW) oligomers, and Irisin are molecules involved in several metabolic processes. To investigate if these cytokines could represent new metabolic markers, we evaluated the expression of Acrp30 and Irisin in serum of obese children from South Italy affected by different degrees of insulin resistance (IR). The anthropometric and metabolic features were evaluated in 27 obese children versus 13 age-matched controls. The expression of Acrp30, its pattern and Irisin were investigated by ELISA, western blotting and fast protein liquid chromatography. The HOMA index was significantly higher in obese children versus controls, and metabolic syndrome was more prevalent in obese children with elevated IR versus those with normal HOMA (38% vs 16%). Total Acrp30 and HMW oligomers were significantly lower in obese than in control children, and the difference was more pronounced in children with HOMA >3.4. In control and obese children, total Acrp30 and HMW oligomers were inversely related to HOMA (r-0.38, p 0.02; r-0.35, p 0.03). Irisin was significantly higher in obese than in control children, and was inversely correlated with Acrp30 and HMW (r-0.32, p 0.04; r-0.39, p 0.01). The inverse correlation of Acpr30 and HMW oligomers with HOMA indicates that Acpr30 is directly involved in IR status. Moreover, the inverse correlation between Irisin and Acrp30 and, more significantly, between Irisin and HMW oligomers suggests that the two cytokines are closely connected. The use of Acrp30, HMW oligomers and Irisin as predictive factors of IR in obese children remains to be further elucidated., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: When the permeability of the glomerular filtration barrier increases, leading to proteinuria, nephrotic syndrome (NS) occurs. First episodes or relapses of NS can be concurrent with acute gastroenteritis (AGE) infections. This condition can cause further deterioration of the hypovolemic state, as intravascular water is lost through both AGE-related vomiting/diarrhea and NS-related fluid shifting into the interstitium. In this case report, we wish to raise the issues about the difficult management of children presenting with both NS and AGE., Case Report: We report two cases characterized by concurrence of NS and AGE. Despite our intervention, case #1 required dialysis, whereas in the case #2 we restored the patient's liquid homeostasis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: No guidelines helping general physicians in the management of children presenting with both NS and AGE are available in the literature. However, it is common for these patients to seek the first line of treatment at emergency departments. In these patients, restoring the liquid homeostasis is a challenge, but some key points can help the physicians with first-line management: 1) carefully evaluate the signs of hypovolemia (edematous state can be misleading); 2) bear in mind that-in hypovolemic, severely hypoalbuminemic (serum albumin levels < 2 g/dL) NS children-initial fluid administration should be followed by a 20% albumin infusion if oligoanuria persists; intravenous 4.5% albumin may be a valid alternative as a first-line therapy instead of crystalloid and 20% albumin; and 3) pay attention when using furosemide; it should only be administered after albumin infusion or after hypovolemia correction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Mutations in the imprinted gene MKRN3 have been described as a common genetic cause of idiopathic central precocious puberty (CPP), in particular in familial cases. However, the exact prevalence of mutations is unknown. Single nucleotide polymorphisms in 2 other imprinted genes, DLK1 and KCNK9, have been associated with age at menarche. We investigated the prevalence of mutations in MKRN3, DLK1, and KCNK9 genes in a cohort of girls with idiopathic CPP., Methods: MKRN3, DLK1, and KCNK9 coding regions were sequenced in 60 girls with idiopathic CPP (familial in 23 cases)., Results: Three mutations, including a new one, in MKRN3 were found in 2 familial cases (c.1229G>A; p.Cys410Ter and c.477&#95;485del; p.Pro160Cysfs*14) (8.7%) and in 1 sporadic case (c.982C>T; p.Arg328Cys) (2.8%). We did not find rare variants in DLK1 and KCNK9 genes., Conclusions: (1) The prevalence of MKRN3 mutations in our cohort was similar to that reported in the literature in sporadic cases but lower than previously described in familial ones. This could be due to different inheritance patterns of families studied; (2) we expanded the phenotype of MKRN3 defects describing 3 more patients with MKRN3 mutations; and (3) point mutations in DLK1 and KCNK9 at least do not seem to be a common cause of CPP in girls., (© 2017 S. Karger AG, Basel.)

Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Context: Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/hypertrophy. Obesity inhibits the "browning" of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce antiobesity effect in mice. A common missense CB2 variant, Q63R, causes CB2-reduced function., Objective: To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of ADP activity and morphology., Design: CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in vitro ADPs obtained from mesenchymal stem cells of adult healthy donors or from sc adipose biopsies of adult nonobese and obese subjects., Setting: Department of Women, Child and General and Specialist Surgery of the Second University of Naples., Patients or Other Participants: A total of 501 obese Italian children (age 11 ± 2.75). Twelve healthy bone marrow donors (age 36.5 ± 15); and 17 subjects, 7 lean (age 42 ± 10) and 10 obese (age 37.8 ± 12) underwent sc adipose tissue biopsies., Main Outcome Measures: Effects of CB2 stimulation on adipokine, perilipin, and uncoupling protein-1 expression., Results: The less-functional CB2-R63 variant was significantly associated with a high z-score body mass index. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects., Conclusion: CB2 receptor is a novel pharmacological target that should be considered for obesity.

Aim: To verify if subclinical hypothyroidism (SCH) could be associated to atopy in children., Methods: Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy, obesity, chronic low grade inflammation, and SCH work up., Results: Four hundred and forty-five out of 705 (63.12%) children affected by allergic disease were diagnosed as atopic and 260 (36.88%) as not atopic. The SCH prevalence was 6.3%. Significant higher prevalence of SCH among atopic children with average (group 2) and high (group 3) low grade chronic inflammation compared to atopic children with mild (group 1) low grade chronic inflammation was present. Moreover, group 1 and group 2 presented an OR to show SCH of 2.57 (95%CI: 1.55-6.26) and 2.96 (95%CI: 1.01-8.65), respectively. Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3 respect to group 2 and group 1. Noteworthy, among atopic patients, also total immunoglobulin E (IgE) serum levels, were significantly higher in group 3 compared to group 2 and group 1 children. In atopic children, C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values, while in not atopic children this phenomenon was not evident., Conclusion: The possibility exists that an increasing atopic inflammation contributes to SCH occurrence. So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.

Background: In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation., Case Presentation: A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months., Conclusions: Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Aims: We aimed at evaluating a standard multiplex ligation-dependent probe amplification (MLPA) probe set for the detection of aneuploidy to diagnose Turner syndrome (TS). We first fixed an MLPA ratio cutoff able to detect all cases of TS in a pilot TS group. We then tested this value on a second group of TS patients and a short-stature population to measure specificity and sensitivity., Methods: 15 TS patients with X mosaicism or X structural abnormalities (Pilot TS Group), 45 TS karyotype-assessed patients (TS Group), and 74 prepubertal female patients with apparent idiopathic short stature (Short-Stature Group) were enrolled. All subjects underwent MLPA and karyotype analysis. In the TS and Short-Stature Groups, MLPA testing was performed in blind., Results: The choice of an MLPA threshold ratio of 0.76 for at least 1 probe allowed us to detect all TS cases, including mosaicisms. Sensitivity and specificity were 100% (CI 95%, 0.92-1) and 88.89% (CI 95%, 0.79-0.94), respectively. The positive predictive value was 88.5%, and the negative predictive value was 100%. MLPA detected the presence of Y chromosome material in 2 patients., Conclusion: MLPA is an accurate and inexpensive tool to screen for TS in girls with short stature. A customized MLPA kit may be useful for the screening of an even larger population., (© 2016 S. Karger AG, Basel.)

Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research.

Background: Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function of this gene is not completely known and the phenotype caused by its defect is not yet fully elucidated. We report a new MKRN3 mutation (Pro160Cysfs*14) causing familial CPP., Case Presentation: The index case is a 7 years old girl showing Tanner stage 3 and pubic hair stage 1. Her bone age evaluated by TW2 method was 10.3 years. Her hormonal data confirmed the diagnosis of central precocious puberty. Familial medical history revealed precocious puberty in a cousin on paternal side. Paternal grandmother had menarche at the age of 9 years and 6 months and premature menopause when she was 36 years old. Genetic analysis revealed a new mutation (c477&#95;485del; Pro160Cysfs*14) in the maternally imprinted MKRN3. Puberty onset was at 5 years in the other affected female family member. Precocious puberty was well controlled by pharmacological therapy., Conclusion: We expand the number of the MKRN3 mutations associated with CPP and highlight the importance of an accurate family medical history to disclose the peculiar pattern of inheritance of this gene.

Background: The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement., Aim: In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls., Methods: We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay., Results: In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1-3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years)., Conclusion: We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls.

Parental anxiety confers risk for the development of an anxiety disorder in children, and this risk may be transmitted through children's stress reactivity. Further, some children may be more vulnerable to reactivity in the presence of parent factors such as anxiety. In this study, we examined whether parents' anxiety symptoms prospectively predict school-aged children's physiological reactivity following stress, assessed through their electrodermal activity (galvanic skin response) during recovery from a performance challenge task, and whether this varies as a function of children's temperamental fearfulness. Parents and their children (N = 68) reported on their anxiety symptoms at Time 1 of data collection, and parents characterized the extent to which their children had fearful temperaments. At Time 2 children completed the performance challenge and two recovery tasks. Greater parental anxiety symptom severity at Time 1 predicted children's higher electrodermal response during both recovery tasks following the failure task. Further, these effects are specific to children with medium and high fearful temperament, whereas for children low in fearfulness, the association between parent anxiety and child reactivity is not significant. Findings provide additional evidence for the diathesis-stress hypothesis and are discussed in terms of their contribution to the literature on developmental psychopathology.

Context: Studies examining vitamin D levels in association with childhood obesity usually do not consider the effect of insulin on vitamin D-binding protein and do not calculate the unbound, bioavailable vitamin D., Objective: This study aimed to evaluate in a group of children 1) the concentrations of both total 25-hydroxyvitamin D and bioavailable fraction, and 2) the potential role of insulin resistance in modulating the concentrations of bioavailable vitamin D. Design, Setting, and Patients or Other Participants: This was a cross-sectional study at a University Pediatric Department in which 63 obese children and 21 lean controls were enrolled., Main Outcome Measures: Total 25-hydroxyvitamin D and vitamin D-binding protein were measured, two single-nucleotide polymorphisms in the coding region of the vitamin D-binding protein (rs4588 and rs7041) were studied, and the vitamin D bioavailable fraction was calculated., Results: Obese children showed total 25-hydroxyvitamin D levels lower compared with nonobese children (21.3 ± 6.7 ng/mL vs 29.6 ± 11.7 ng/mL; P = .0004). Bioavailable 25-hydroxyvitamin D levels were not different among the two groups (3.1 ± 1.6 ng/mL vs 2.6 ± 1.2 ng/mL; P > .05). Insulin-resistant children showed higher bioavailable levels of 25-hydroxyvitamin D compared with noninsulin-resistant children (3.4 ± 1.4 ng/mL vs 2.0 ± 0.9 ng/mL; P = .013) and an inverse correlation between insulin resistance and vitamin D-binding protein was found (r:= -0.40; P = .024)., Conclusions: Obese children present levels of bioavailable 25-hydroxyvitamin D similar to those of normal-weight children due to reduced concentration of vitamin D-binding protein. The insulin resistance could play a role in this reduced concentration.

Objectives: Studies of adults and children with celiac disease have reported an increased risk of overweight during gluten-free diet (GFD). The fat mass and obesity-associated gene (FTO) variant rs9939609 has been associated with increased risk of developing obesity in children and adults., Methods: In our study, we analyzed the effect of this variant on weight gain in a cohort of 280 children with celiac disease on GFD., Results: We found that after a mean follow-up time of 3.0 years on GFD, FTO polymorphism influenced significantly the mean change in body mass index z score (P = 0.01)., Conclusions: We conclude that the FTO gene contributes to determine weight changes in children with celiac disease on GFD.

Classically, the non-alcoholic fatty liver disease (NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis (NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148M, GPR120 R270H and TM6SF2 E167K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity. Therefore, it is involved in the first hit, such as TM6SF2 E167K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.

Background: The prevalence of obesity is increasing among children/adolescents. Subtle cardiovascular abnormalities, responsible for a higher mortality later in life, have been reported in obese children/adolescents. The aims of the study were to evaluate cardiovascular autonomic regulation, by means of spectrum analysis of R-R interval variability, and myocardial function, by means of standard and tissue Doppler echocardiography, in a group of non-hypertensive asymptomatic obese children and adolescents; furthermore, the influence of insulin resistance was tested., Subjects and Methods: R-R interval variability was analyzed during both the 70° head-up tilt and 24-hour electrocardiographic holter monitoring. Spectrum analysis of R-R interval variability provided the indices of sympathetic (low frequency [LFRR]) and vagal (high frequency [HFRR]) modulation of the sinoatrial node. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to classify obese children/adolescents (n=72) as insulin resistant (n=37) and non-insulin resistant (n=35)., Results: In obese subjects: a) left ventricular mass was significantly (p<0.05) increased, whereas both the e/a ratio and the e'/a' ratio were decreased; b) at rest, HFRR was lower, and the LFRR/HFRR ratio was higher; c) during tilting, magnitude of tilt-induced inhibition of HFRR was lower; d) during 24-hour electrocardiographic holter monitoring, LFRR and the LFRR/HFRR ratio were higher, whereas HFRR was lower; e) HOMA-IR inversely correlated with both the e'/a' ratio (r=-0.655; p<0.001) and the tilt-induced LFRR/HFRR ratio (r=-0.933; p<0.001); and, f) the e'/a' ratio correlated with the tilt-induced LFRR/HFRR ratio (r=0.501; p<0.001). Moreover, HFRR at rest, magnitude of tilt-induced HFRR reduction, and the e'/a' ratio in insulin resistant obese children/adolescents were markedly lower when compared with the remaining subjects., Conclusions: Subclinical abnormalities of myocardial function and of cardiac autonomic regulation were closely associated in obese children/adolescents and both correlated with the degree of insulin resistance.

The G-protein-coupled receptor 120 (GPR120) is a receptor for polyunsaturated fatty acids with anti-inflammatory activity. The R270H variant of GPR120 enhances inflammation in adipose and hepatic tissues. We investigated whether the R270H variant could play a role in determining liver injury in children and adolescents with obesity. Five hundred eighty-one children with obesity were studied. No homozygotes and 20 heterozygotes for the 270H allele were found. Heterozygotes showed higher alanine transaminase (ALT) levels (P = 0.01) than wild-type subjects, and also showed an odds ratio to have pathologic ALT of 3.2 (95% confidence interval [CI] 1.2-8.0, P < 0.05). Moreover, we genotyped the same patients for the patatin-like phospholipase-containing domain 3 (PNPLA3) I148M polymorphism, which is implicated in the development of liver steatosis. Stratifying the patients with the GPR120 270H variant on the basis of their PNPLA3 polymorphism, we demonstrated a significant interaction effect on ALT levels (P = 0.00001), suggesting a driving effect of the PNPLA3 148M allele on liver injury in children with obesity carrying this variant.

Objective: Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction consequent to the exposure to causal allergen. Resveratrol is a natural non-flavonoid polyphenol, exerting anti-inflammatory activity; β-glucan is a polysaccharide with immuno-modulatory properties. Thus, this study aimed to investigate whether these combined compounds are able of relieving nasal symptoms in children with AR due to pollen allergy., Research Design and Methods: The present study was conducted as placebo-controlled, double-blinded, and randomized. Globally, 68 children (36 males; mean age 7.9 years) were treated with resveratrol plus β-glucan or placebo (the diluent of active drug) two sprays (100 µL/spray) in each nostril three times/day for 2 months. Nasal symptoms, including itching, sneezing, rhinorrhea, and obstruction, were assessed at baseline and after treatment. Use of rescue medication, such as cetirizine syrup, was also evaluated., Clinical Trial Registration: ClinicalTrials.gov ID NCT02130440., Results: Children treated with active drug achieved a significant reduction in all nasal symptoms: itching (p = 0.0001), sneezing (p = 0.0009), rhinorrhea (p = 0.009), and obstruction (0.002) as well as antihistamine use (p = 0.003). Placebo did not affect nasal complaints and cetirizine use. The intergroup analysis showed that active treatment was significantly superior to placebo about reduction of AR symptoms and rescue medication use., Conclusions: The present preliminary study firstly showed that intranasal resveratrol plus carboxymethyl-β-glucan is capable of significantly improving nasal symptoms in children with pollen-induced AR.

Context: Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects., Objective: The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance., Design and Setting: Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents., Results: At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P < .05) greater than in referent subjects, whereas high-density lipoprotein cholesterol and HFRR were lower; meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P < .001) with meal-induced changes in the LFRR to HFRR ratio among obese subjects., Conclusions: Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

Objective: To evaluate normoglycemic overweight/obese (Ow/Ob) children whose post-load plasma glucose (2hPG) cut-point may be significantly associated with cardiometabolic risk factors (CMRFs) and whether this cut-point predicts preclinical signs of organ damage., Methods: One thousand seven hundred and thrity four normoglycemic Ow/Ob children were stratified into quintiles of 2hPG, the sixth group was constituted by 101 children with impaired glucose tolerance (IGT)., Results: Moving from the lower quintiles of 2hPG to IGT, the groups differed for Prepubertal stage, BMI, fasting PG, insulin levels, blood pressure, and lipids. To evaluate the best cut-off of 2hPG related to CMRFs, the area under the receiver operating characteristic curve and the Youden's index was calculated. Insulin resistance, high blood pressure, and high triglyceride/HDL-C ratio were associated with a 2hPG cut-off of 110 mg/dl. Children with 2hPG ≥110 mg/dl showed 1.3-3.2 fold higher risk to have high levels of ALT (as surrogate of nonalcoholic fatty liver disease) or increased carotid intima-media thickness., Conclusions: This study, performed in a large cohort of Ow/Ob children, shows that an atherogenic risk profile and preclinical signs of organ damage are associated with post-challenge elevations in plasma glucose still considered in the high normal range., (Copyright © 2014 The Obesity Society.)

Background: The epidemiological decrease of Helicobacter pylori (Hp) infection has been recently associated to the increase of several extra-intestinal allergic disorders., Objective: We investigated the role of specific Hp IgG production in the development of IgE or not IgE mediated food allergy (FA) in children affected by atopic dermatitis (AD)., Methods: From January 2010 to July 2013, 290 South Italian children, aged between 26 and 142 months, were consecutively referred to the Pediatric Clinic of the Pediatric Department at Second University of Naples and were diagnosed as affected by AD. The patients were classified in two groups on the basis of diagnosis of food allergy (88 FA affected and 202 not FA affected) and further divided on the basis of the diagnosis of atopy (63 IgE mediated and 23 not IgE mediated). Hp serum IgG was detected using an enzyme linked immunosorbent assay (ELISA) kit (Wampole® Helicobactor pylori IgG ELISA II, Wampole Laboratories, Cranbury, NJ) and Hp stool antigens using enzyme immunoassay (Premier Platinum HpSa plus, Cincinnati OH)., Results: We found a statistically significant higher prevalence of Hp serology positivity in not FA vs. FA AD-affected children (p = 0.032) and a significant inverse association between FA and Hp immunization (1/OR 0.32 95% CI 0.11-0.95). Further, we identified an absolute prevalence Hp serology positivity in not-IgE-mediated rather than in IgE-mediated FA AD-affected patients (p = 0.0006)., Conclusion: We hypothesize that specific Hp IgG production could protect against the development of both FA and atopy in AD-affected children.

Background & Aims: The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection., Methods: We studied 169 consecutive patients with asymptomatic chronic hepatitis (tested positive for anti-HCV and HCV RNA) at 2 liver units in southern Italy. First, liver biopsy samples were collected from July 2009 through December 2011. All patients were naive to antiviral therapy; CNR2 genotype was determined by polymerase chain reaction analysis., Results: Patients with the CB2-63 QQ variant had higher serum levels of aminotransferase than those with the CB2-63 QR or RR variants; they also had higher histologic activity index (HAI) scores (8.6 ± 3.8) than patients without the CB2-63 RR variant (5.3 ± 3.6; P < .005) or those with the CB2-63 QR variant (5.8 ± 3.3; P < .001). Patients with the different variants of CNR2 did not differ in fibrosis stage or steatosis score. Moderate or severe chronic hepatitis (HAI score, >8) was identified more frequently (55.5%) in patients with the CB2-63 QQ variant than in those with the 63 QR (20%; P < .005) or RR variants (17.4%; P < .005). In logistic regression analysis, the CB2-63 QQ variant and fibrosis score were independent predictors of moderate or severe chronic hepatitis (HAI score, >8; P < .0001)., Conclusions: The CB2-63 QQ variant of CNR2 is associated with more severe inflammation and hepatocellular necrosis in patients with HCV infection., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)