Resilience strengthening in youth with a chronic medical condition: a randomized controlled feasibility trial of a combined app and coaching program.

Youth with a chronic medical condition (CMC) are often affected by comorbid mental disorders. Resilience-strengthening interventions can protect youth's mental health, yet evidence-based programs remain scarce. To address this lack, this study aimed to evaluate the feasibility of a dual approach combining app-based resilience training and cognitive behavioral group coaching. Fifty-one youths with CMC treated at a German university children's hospital aged 12-16 years were recruited. They were randomly assigned to a combined app game and coaching intervention or sole app gameplay. At pre-, post-intervention, and at a 2-month follow-up resilience, automatic negative thoughts and an app and coaching evaluation were assessed. Feasibility was defined as a recruitment rate of 70%, an 85% adherence rate for the REThink game, and 70% participation in both coaching sessions. Feasibility criteria were reached for coaching participation but not for recruitment or app adherence. While both the REThink game app and coaching intervention had high acceptance rates among youth with CMC, participants receiving additional coaching sessions showed higher satisfaction and adherence rates. Participants preferred remote to in-person meetings. The findings support a combination of a gamification app approach with online group coaching. Group coaching can improve adherence while online options increase accessibility. Future research should focus on testing in diverse participant samples, language, and age-adapted updates of the REThink game app. These findings provide guidance for increasing adherence in future intervention studies in youth with CMC cohorts.

Altered DNA methylation at age-associated CpG sites in children with growth disorders: impact on age estimation?

Age estimation based on DNA methylation (DNAm) can be applied to children, adolescents and adults, but many CG dinucleotides (CpGs) exhibit different kinetics of age-associated DNAm across these age ranges. Furthermore, it is still unclear how growth disorders impact epigenetic age predictions, and this may be particularly relevant for a forensic application. In this study, we analyzed buccal mucosa samples from 95 healthy children and 104 children with different growth disorders. DNAm was analysed by pyrosequencing for 22 CpGs in the genes PDE4C, ELOVL2, RPA2, EDARADD and DDO. The relationship between DNAm and age in healthy children was tested by Spearman's rank correlation. Differences in DNAm between the groups "healthy children" and the (sub-)groups of children with growth disorders were tested by ANCOVA. Models for age estimation were trained (1) based on the data from 11 CpGs with a close correlation between DNAm and age (R ≥ 0.75) and (2) on five CpGs that also did not present significant differences in DNAm between healthy and diseased children. Statistical analysis revealed significant differences between the healthy group and the group with growth disorders (11 CpGs), the subgroup with a short stature (12 CpGs) and the non-short stature subgroup (three CpGs). The results are in line with the assumption of an epigenetic regulation of height-influencing genes. Age predictors trained on 11 CpGs with high correlations between DNAm and age revealed higher mean absolute errors (MAEs) in the group of growth disorders (mean MAE 2.21 years versus MAE 1.79 in the healthy group) as well as in the short stature (sub-)groups; furthermore, there was a clear tendency for overestimation of ages in all growth disorder groups (mean age deviations: total growth disorder group 1.85 years, short stature group 1.99 years). Age estimates on samples from children with growth disorders were more precise when using a model containing only the five CpGs that did not present significant differences in DNAm between healthy and diseased children (mean age deviations: total growth disorder group 1.45 years, short stature group 1.66 years). The results suggest that CpGs in genes involved in processes relevant for growth and development should be avoided in age prediction models for children since they may be sensitive for alterations in the DNAm pattern in cases of growth disorders.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.