Defining and Measuring Resilience in Children with a Chronic Disease: a Scoping Review

UNLABELLED: More than 25% of all children grow up with a chronic disease. They are at higher risk for developmental and psychosocial problems. However, children who function resiliently manage to adapt positively to these challenges. We aim to systematically review how resilience is defined and measured in children with a chronic disease. A search of PubMed, Cochrane, Embase, and PsycINFO was performed on December 9, 2022, using resilience, disease, and child/adolescent as search terms. Two reviewers independently screened articles for inclusion according to predefined criteria. Extraction domains included study characteristics, definition, and instruments assessing resilience outcomes, and resilience factors. Fifty-five out of 8766 articles were identified as relevant. In general, resilience was characterized as positive adaptation to adversity. The included studies assessed resilience by the outcomes of positive adaptation, or by resilience factors, or both. We categorized the assessed resilience outcomes into three groups: personal traits, psychosocial functioning, and disease-related outcomes. Moreover, myriad of resilience factors were measured, which were grouped into internal resilience factors (cognitive, social, and emotional competence factors), disease-related factors, and external factors (caregiver factors, social factors, and contextual factors). Our scoping review provides insight into the definitions and instruments used to measure resilience in children with a chronic disease. More knowledge is needed on which resilience factors are related to positive adaptation in specific illness-related challenges, which underlying mechanisms are responsible for this positive adaptation, and how these underlying mechanisms interact with one another. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42844-023-00092-2

Tracking Mental Wellbeing of Dutch Adolescents During the First Year of the COVID-19 Lockdown: A Longitudinal Study

Purpose: Adolescents might be susceptible to the effects of the COVID-19 lockdown. We assessed changes in mental wellbeing throughout the first year of the pandemic and compared these with prepandemic levels. Methods: This five-wave prospective study among Dutch adolescents aged 12–17 years used data collected before the pandemic (n = 224) (T0), in May (T1), July (T2), and October 2020 (T3), and in February 2021 (T4). Generalized estimating equations were used to assess the association between stringency of the lockdown with mental wellbeing. Results: Adolescents had a lower life satisfaction during the first full lockdown (T1) [adjusted β: −0.36, 95% confidence interval (CI): −0.58 to −0.13], during the partial lockdown (T3) (adjusted β: −0.37, 95% CI: −0.63 to −0.12), and during the second full lockdown (T4) (adjusted β: −0.79, 95% CI: −1.07 to −0.52) compared to before the pandemic (T0). Adolescents reported more internalizing symptoms during only the second full lockdown (T4) (adjusted β: 2.58, 95% CI: 0.41–4.75). During the pandemic [at T1 (adjusted β: 0.29, 95% CI: 0.20–0.38), T2 (adjusted β: 0.36, 95% CI: 0.26–0.46), T3 (adjusted β: 0.33, 95% CI: 0.22–0.45), and T4 (adjusted β: 0.20, 95% CI: 0.07–0.34)], adolescents reported a better psychosomatic health, partly attributable to less trouble falling asleep (p < .01). Discussion: The COVID-19 lockdown measures have had both a negative and positive impact on mental wellbeing of Dutch adolescents. However, mental wellbeing was most impacted during the second full lockdown compared to before the pandemic

The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism

Inborn errors of metabolism (IEMs) comprise a diverse group of individually rare monogenic disorders that affect metabolic pathways. Mutations lead to enzymatic deficiency or dysfunction, which results in intermediate metabolite accumulation or deficit leading to disease phenotypes. Currently, treatment options for many IEMs are insufficient. Rarity of individual IEMs hampers therapy development and phenotypic and genetic heterogeneity suggest beneficial effects of personalized approaches. Recently, cultures of patient-own liver-derived intrahepatic cholangiocyte organoids (ICOs) have been established. Since most metabolic genes are expressed in the liver, patient-derived ICOs represent exciting possibilities for in vitro modeling and personalized drug testing for IEMs. However, the exact application range of ICOs remains unclear. To address this, we examined which metabolic pathways can be studied with ICOs and what the potential and limitations of patient-derived ICOs are to model metabolic functions. We present functional assays in patient ICOs with defects in branched-chain amino acid metabolism (methylmalonic acidemia), copper metabolism (Wilson disease), and transporter defects (cystic fibrosis). We discuss the broad range of functional assays that can be applied to ICOs, but also address the limitations of these patient-specific cell models. In doing so, we aim to guide the selection of the appropriate cell model for studies of a specific disease or metabolic process

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed n

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Gender-Specific Changes in Life Satisfaction After the COVID-19-Related Lockdown in Dutch Adolescents: A Longitudinal Study

Purpose: The purposes of this study were to assess whether mental well-being has changed after introduction of the lockdown measures compared with that before, whether this change differs between boys and girls, and whether this change is associated with COVID-19–related concerns. Methods: This is a two-wave prospective study among Dutch adolescents using data collected up to one year before the COVID-19 pandemic (n = 224) and 5–8 weeks after the first introduction of lockdown measures (n = 158). Mental well-being was assessed by three indicators: life satisfaction, internalizing symptoms, and psychosomatic health. General linear model repeated-measures analysis of variance was used to assess whether mental well-being has changed and if this differed by sex. Univariate linear regressions were used to assess associations between COVID-19–related concerns and a change in mental well-being. Results: Life satisfaction decreased (η2p = .079, p < .001), but no change in internalizing symptoms was observed (η2p = .014, p = .14), and psychosomatic health increased (η2p = .194, p < .001) after the introduction of lockdown measures. Boys scored significantly better on all mental health indicators compared with girls at baseline and follow-up. However, boys' life satisfaction significantly decreased at the follow-up (η2p = .038, p = .015), whereas girls' life satisfaction did not change. Concerns about COVID-19 were significantly associated with a lower life satisfaction and more internalizing symptoms. Conclusions: Adolescents', especially boys', life satisfaction decreased during the lockdown. They reported no change in internalizing symptoms and an improved psychosomatic health. Adolescents' mental well-being is expected to vary during the COVID-19 pandemic and should continue to be monitored

Mental Wellbeing and General Health in Adolescents with Asthma: The PIAMA Birth Cohort Study.

Objectives To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma. Study design Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental wellbeing and perceived general health using generalized estimating equations. Results At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages. Conclusions The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health

Mental Well-being and General Health in Adolescents with Asthma: The Prevention and Incidence of Asthma and Mite Allergy Birth Cohort Study

OBJECTIVES: To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma. STUDY DESIGN: Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental well-being and perceived general health using generalized estimating equations. RESULTS: At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages. CONCLUSIONS: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health

Tracking Mental Wellbeing of Dutch Adolescents During the First Year of the COVID-19 Lockdown: A Longitudinal Study

Purpose: Adolescents might be susceptible to the effects of the COVID-19 lockdown. We assessed changes in mental wellbeing throughout the first year of the pandemic and compared these with prepandemic levels. Methods: This five-wave prospective study among Dutch adolescents aged 12–17 years used data collected before the pandemic (n = 224) (T0), in May (T1), July (T2), and October 2020 (T3), and in February 2021 (T4). Generalized estimating equations were used to assess the association between stringency of the lockdown with mental wellbeing. Results: Adolescents had a lower life satisfaction during the first full lockdown (T1) [adjusted β: −0.36, 95% confidence interval (CI): −0.58 to −0.13], during the partial lockdown (T3) (adjusted β: −0.37, 95% CI: −0.63 to −0.12), and during the second full lockdown (T4) (adjusted β: −0.79, 95% CI: −1.07 to −0.52) compared to before the pandemic (T0). Adolescents reported more internalizing symptoms during only the second full lockdown (T4) (adjusted β: 2.58, 95% CI: 0.41–4.75). During the pandemic [at T1 (adjusted β: 0.29, 95% CI: 0.20–0.38), T2 (adjusted β: 0.36, 95% CI: 0.26–0.46), T3 (adjusted β: 0.33, 95% CI: 0.22–0.45), and T4 (adjusted β: 0.20, 95% CI: 0.07–0.34)], adolescents reported a better psychosomatic health, partly attributable to less trouble falling asleep (p < .01). Discussion: The COVID-19 lockdown measures have had both a negative and positive impact on mental wellbeing of Dutch adolescents. However, mental wellbeing was most impacted during the second full lockdown compared to before the pandemic