Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.

Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF-II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway

Interaction Effects of Child Weight Status and Parental Feeding Practices on Children’s Eating Disorder Symptomatology

(1) Background: Research on parental feeding practices and non-normative eating behavior including loss of control (LOC) eating and eating disorder psychopathology indicated separate associations of these variables with child weight status, especially in early childhood. This study cross-sectionally examined interaction effects of restriction, monitoring, pressure to eat, and children’s weight status on disordered eating in children aged 8–13 years. (2) Methods: A population-based sample of N = 904 children and their mothers completed the Eating Disorder Examination Questionnaire for Children and the Child Feeding Questionnaire. Child anthropometrics were objectively measured. Hierarchical linear and logistic regression analyses were conducted for cross-sectionally predicting global eating disorder psychopathology and recurrent LOC eating by feeding practices and child weight status for younger (8–10 years) and older (11–13 years) ages. (3) Results: Restriction x Child weight status significantly predicted global eating disorder psychopathology in younger children and recurrent LOC eating in older children. Monitoring x Child weight status significantly predicted eating disorder psychopathology in older children. A higher versus lower child weight status was associated with adverse eating behaviors, particularly in children with mothers reporting high restriction and monitoring. (4) Conclusions: Detrimental associations between higher child weight status and child eating disorder symptomatology held especially true for children whose mothers strongly control child food intake

Insulin-Like Growth Factor (IGF)-I and -11 and IGFBinding Proteins-l, -2, and -3 in Children and Adolescents with Diabetes Mellitus: Correlation with Metabolic Control and Height Attainment.

The putative effects of diabetes and metabolic control on circulating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) remain controversial. In the present study, serum levels of IGF-I and IGF-II and IGFBP-1, -2, and -3 were measured in 58 patients (age, 0.8-17 yr) with treated (51 subjects) or untreated (7 subjects) insulin-dependent diabetes mellitus (IDDM) and were compared with the levels in normal subjects. In the untreated patients IGF-I and IGF-II were decreased as compared with the healthy controls. In the treated diabetics IGF-I and IGF-II were reduced; IGFBP-2 (only in prepubertal subjects) and IGFBP-3 were increased. Furthermore, age-adjusted values of IGF-I, IGF-II, and IGFBP-3 were lower in prepubertal than in pubertal patients. Regression analysis revealed a negative correlation between hemoglobin (Hb)A1c and standard deviation scores (SDS) of IGF-I and a positive association between HbA1c and IGFBP-1 SDS or IGFBP-2 SDS. In the treated patients HbA1c was positively related to IGFBP-1 SDS and IGFBP-2 SDS when applying simple regression analysis and to IGFBP-2 SDS when using a multiple regression model. Strong correlations were observed between height SDS and IGF-I SDS, IGF-II SDS, and IGFBP-3 SDS in prepubertal subjects who had had IDDM for at least 2 yr, but not in adolescents. Such correlations have also been found in healthy children and adolescents. In conclusion; 1) IDDM is associated with alterations of the IGF-IGFBP system, which are partially accounted for by differences in metabolic control and pubertal status; 2) the lower plasma concentrations of serum IGF-I may play a role in the pathogenesis of growth impairment of poorly controlled prepubertal, but not pubertal, children and adolescents with IDDM; and 3) in addition, a potential role of the altered IGF-IGFBP system for the development of diabetic late complications is hypothesized

Interview-based assessment of avoidant/restrictive food intake disorder (ARFID): A pilot study evaluating an ARFID module for the Eating Disorder Examination

Objective Although avoidant/restrictive food intake disorder (ARFID) has been included as a new diagnostic entity of childhood feeding and eating disorders, there is a lack of measures to reliably and validly assess ARFID. In addition, virtually nothing is known about clinical characteristics of ARFID in nonclinical samples. Method The present study presents the development and validation of an ARFID module for the child and parent version of the Eating Disorder Examination (EDE) in a nonclinical sample of N = 39 children between 8 and 13 years with underweight and/or restrictive eating behaviors. For evaluating the ARFID module's reliability, the convergence of diagnoses between two independent raters and between the child and parent module was determined. The module's validity was evaluated based on the full-length child version of the EDE, a 24 h food record, parent-reported psychosocial functioning and self-reported quality of life, and objective anthropometric measures. Results In total, n = 7 children received an ARFID diagnosis. The ARFID module showed high interrater reliability, especially for the parent version, and high convergence between child and parent report. Evidence for the module's convergent, divergent, and discriminant validity was provided. Specifically, children with versus without ARFID reported significantly less macro- and micronutrient intake and were more likely to be underweight. Discussion This pilot study indicates the child and parent version of the EDE ARFID module to be promising for diagnosing ARFID in a structured way but still necessitates a validation in a larger clinical and community-based sample

Characteristics of avoidant/restrictive food intake disorder in a general pediatric inpatient sample

Objective: Although patients with avoidant/restrictive food intake disorder (ARFID) often consult general pediatric services initially, existing literature mostly concentrated on ntensive eating disorder treatment settings. This cross-sectional study sought to describe symptoms of ARFID and their associations with eating disorder psychopathology, quality of life, anthropometry, and physical comorbidities in a general pediatric sample. Methods: In N = 111 patients (8-18 years) seeking treatment for physical diseases, prevalence of ARFID-related restrictive eating behaviors was estimated by self-report and compared to population-based data (N = 799). Using self-report and medical record data, further ARFID diagnostic criteria were evaluated. Patients with versus without symptoms of ARFID based on self-report and medical records were compared in diverse clinical variables. Results: The prevalence of self-reported symptoms of ARFID was not higher in the inpatient than population-based sample. Only picky eating and shape concern were more common in the inpatient than population-based sample. Although 69% of the inpatient sample reported any restrictive eating behaviors, only 7.2% of patients showed symptoms of ARFID based on medical records in addition to self-report, particularly those with underweight, without significant effects for age, sex, and medical diagnoses. Discussion: The study revealed the importance of considering ARFID within the treatment of children and adolescents with physical diseases, especially for those with underweight. Further research is needed to replicate the findings with interview-based measures and to investigate the direction of effects in ARFID and its physical correlates

Media Use of Mothers, Media Use of Children, and Parent–Child Interaction Are Related to Behavioral Difficulties and Strengths of Children

The present study investigated the associations of media use of children, media use of mothers, and parent-child interactions with behavioral strengths and difficulties in children. Screen time of 553 2- to 9-year-old children and their mothers were indicated by the daily durations of their TV/games console/computer/mobile phone use. The amount of parent–child interaction was indicated by the frequencies of shared activities at home. Behavioral strengths and difficulties of children were investigated using the Strengths and Difficulties Questionnaire. Children whose mothers reported high screen times (>/= 5 h/day) were significantly more likely to show high screen times (>/= 2 h/day). High screen time of children was associated with more conduct problems, more symptoms of hyperactivity/inattention and less prosocial behavior. High screen time of mothers was associated with emotional problems, conduct problems, and symptoms of hyperactivity/inattention. In contrast, a higher frequency of parent–child interactions was associated with fewer conduct problems, fewer peer-relationship problems, and more prosocial behavior of children. Children might use the media behavior of their mothers as a role model for their own media use. Furthermore, the findings suggest that media use of children and mothers and parent–child interaction contribute independently to behavioral strengths and difficulties of children

Relationship between Age-Dependent Body Constitution and Temporomandibular Joint Sounds in Adolescents

To date, risk factors for temporomandibular joint (TMJ) sounds are still not completely understood, and anatomical factors are suspected to influence their occurrence. This study aimed to evaluate the impact of body constitution on temporomandibular joint sounds of adolescents. 10- to 18-year-old participants of the LIFE Child Study were examined for TMJ sounds, and physical parameters such as body height, body weight, and general laxity of joints were measured. Odds ratios (OR) for associations of TMJ sounds and standard deviation scores (SDS) of body height and body weight were calculated by using binary logistic regression, including cofactors such as age and number of hypermobile joints. The OR for TMJ sounds and SDS of body height was 1.28 (95% confidence interval (CI) 1.06; 1.56) in females when the age-adjusted height value was above 0. SDS of body weight indicated significant ORs for TMJ sounds in males with values of 0.81 (95% CI 0.70; 0.94). No correlation was detected for SDS values and TMJ crepitus. Tall female adolescents seem to be more prone to TMJ clicking sounds, while their occurrence seems less likely in male adolescents with higher body weight

FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children: relevance of FTO variants to defend body weight in lean children?

Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. Conclusion: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children

The Influence of Steroid Hormones on Tooth Wear in Children and in Adolescents

(1) Background: From a young age, boys are more often affected by tooth wear than girls. This suggests an influence of the male sex hormone (testosterone) on the aetiology of tooth wear. The aim of the present study was to investigate the incidence of tooth wear in relation to steroid hormone levels in children. (2) Methods: 1022 test persons aged between 10 and 18 (491 male, 531 female) from the LIFE Child study underwent medical and dental examination. Tooth wear was measured through clinical inspection. Blood samples were taken to determine hormone levels (testosterone, SHBG). The level of free testosterone was calculated from the ratio of testosterone to SHBG. Using multivariable methods, the incidence of tooth wear was analyzed as a function of hormone levels, while controlling for confounders such as age, sex, social status, and orthodontic treatment. (3) Results: The incidence of tooth wear increased with age in both sexes. Boys showed significantly more often attrition facets than girls (17.5% vs. 13.2%, p < 0.001). Subjects with tooth wear showed significantly higher free testosterone levels than those without (males: p < 0.001, females: p < 0.05). After controlling for confounding variables, the risk of tooth wear increased by approximately 30.0% with each year of life (odds ratio [OR]boys = 1.29, 95% confidence interval [CI] = 1.04–1.56; [OR]girls = 1.32, 95% CI = 1.08–1.61). In addition, the risk of tooth wear increased by 6.0% per free testosterone scale score only in boys (OR = 1.06, 95% CI = 1.01–1.12). (4) Conclusions: Tooth wear is common in children and in adolescents, and it increases steadily with age in both sexes. The stronger increase and the higher prevalence among male adolescents can be explained by the additional effect of free testosterone

An 8-item short form of the Eating Disorder Examination-Questionnaire adapted for children (ChEDE-Q8)

Objective: Eating disturbances are common in children placing a vulnerable group of them at risk for full-syndrome eating disorders and adverse health outcomes. In order to provide a valid self-report assessment of eating disorder psychopathology in children, a short form of the child version of the Eating Disorder Examination (ChEDE-Q) was psychometrically evaluated. Similar to the EDE-Q, the ChEDE-Q provides assessment of eating disorder psychopathology related to anorexia nervosa, bulimia nervosa, and binge-eating disorder. However, it does not assess symptoms of avoidant/restrictive food intake disorder, pica, or rumination disorder. Method: In 1836 participants ages 7 to 18 years, recruited from two independent population-based samples, the factor structure of the recently established 8-item short form EDE-Q8 for adults was examined, including measurement invariance analyses on age, gender, and weight status derived from objectively measured weight and height. For convergent validity, the ChEDE-Q global score, Body Esteem Scale, Strengths and Difficulties Questionnaire, and sociodemographic characteristics were used. Item characteristics and age- and gender-specific norms were calculated. Results: Confirmatory factor analysis revealed good model fit for the 8-item ChEDE-Q. Measurement invariance analyses indicated strict invariance for all analyzed subgroups. Convergent validity was provided through associations with well-established questionnaires and age, gender, and weight status, in expected directions. Discussion: The newly developed ChEDE-Q8 proved to be a psychometrically sound and economical self-report assessment tool of eating disorder psychopathology in children. Further validation studies are needed, particularly concerning discriminant and predictive validity