Preclinical and clinical studies on the co-regulation of tumor-induced angiogenesis and dendritic cell suppression

Giaccone, G. [Promotor]Hoekman, K. [Copromotor]Gruijl, T.D. de [Copromotor

Socioeconomic hardship, uncertainty about the future, and adolescent mental wellbeing over a year during the COVID-19 pandemic

Socioeconomic vulnerabilities put adolescents at risk for mental wellbeing issues, also in times of a pandemic. In the present longitudinal online survey study, we explored changes in mental wellbeing (i.e., mood and life satisfaction) during the COVID-19 pandemic. Second, we examined how socioeconomic hardship in online home schooling predicted adolescents’ mental wellbeing 1 year later. Third, we tested whether this relation was mediated by feelings of uncertainty about the future. Fourth, we tested whether this relation was moderated (in terms of a protective factor) by self-efficacy. In total, 177 Dutch-speaking adolescents aged 10–18 years (Mage = 15.64, SDage = 1.72, 79% females) participated in all three 6-month separated waves (T1 = May 2020, T2 = November 2020, and T3 = May 2021). Mood results demonstrated that feelings of vigor decreased between T1 and T2, and feelings of tension and depression increased between T1, T2, and T3. Socioeconomic hardship in online home schooling in the early phase of the pandemic was negatively associated with both baseline mental wellbeing and 1 year later. Socioeconomic hardship at T1 predicted higher feelings of future uncertainty at T2, and higher levels of future uncertainty were associated with lower feelings of vigor, and higher feelings of tension and depression at T3. However, we found no evidence for mediation or moderation effects. In conclusion, the present findings illustrate the complexity of disentangling the adverse effects of socioeconomic hardship on adolescent mental wellbeing.</p

From developmental neuroscience to policy:A novel framework based on participatory research

Insights from developmental neuroscience are not always translated to actionable policy decisions. In this review, we explore the potential of bridging the gap between developmental neuroscience and policy through youth participatory research approaches. As the current generation of adolescents lives in an increasingly complex and rapidly changing society, their lived experiences are crucial for both research and policy. Moreover, their active involvement holds significant promise, given their heightened creativity and need to contribute. We therefore advocate for a transdisciplinary framework that fosters collaboration between developmental scientists, adolescents, and policy makers in addressing complex societal challenges. We highlight the added value of adolescents' lived experiences in relation to two pressing societal issues affecting adolescents’ mental health: performance pressure and social inequality. By integrating firsthand lived experiences with insights from developmental neuroscience, we provide a foundation for progress in informed policy decisions.</p

From developmental neuroscience to policy:A novel framework based on participatory research

Insights from developmental neuroscience are not always translated to actionable policy decisions. In this review, we explore the potential of bridging the gap between developmental neuroscience and policy through youth participatory research approaches. As the current generation of adolescents lives in an increasingly complex and rapidly changing society, their lived experiences are crucial for both research and policy. Moreover, their active involvement holds significant promise, given their heightened creativity and need to contribute. We therefore advocate for a transdisciplinary framework that fosters collaboration between developmental scientists, adolescents, and policy makers in addressing complex societal challenges. We highlight the added value of adolescents' lived experiences in relation to two pressing societal issues affecting adolescents’ mental health: performance pressure and social inequality. By integrating firsthand lived experiences with insights from developmental neuroscience, we provide a foundation for progress in informed policy decisions.</p

Defective Differentiation of Myeloid and Plasmacytoid Dendritic Cells in Advanced Cancer Patients is not Normalized by Tyrosine Kinase Inhibition of the Vascular Endothelial Growth Factor Receptor

Tumor-derived vascular endothelial growth factor (VEGF) has previously been identified as a causative factor in the disturbed differentiation of myeloid dendritic cells (DC) in advanced cancer patients. Here, we investigated the potential of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase (TK) inhibition to overcome this defective DC differentiation. To this end, peripheral blood DC (PBDC) precursor and subset frequencies were measured in 13 patients with advanced cancer before and after treatment with AZD2171, a TK inhibitor (TKI) of VEGFR, coadministered with gefitinib, and an epidermal growth factor receptor (EGFR) TKI. Of note, not only myeloid DC but also plasmacytoid DC frequencies were significantly reduced in the blood of the cancer patients prior to treatment, as compared to healthy controls. Moreover, besides an accumulated population of immature myeloid cells (ImC), a population of myeloid suppressor cells (MSC) was significantly increased. Upon systemic VEGFR TK inhibition, DC frequencies did not increase, whereas the rate of circulating MSC showed a slight, but not significant, decrease. In conclusion, TK inhibition of VEGFR with AZD2171 does not restore the defective PBDC differentiation observed in advanced cancer patients

The Role of the Epinephrine Test in the Diagnosis and Management of Children Suspected of Having Congenital Long QT Syndrome

The epinephrine test has been shown to be a powerful tool to predict the genotype of congenital long QT syndrome (LQTS). The aim of this study was to evaluate its role in the diagnosis and management of LQTS in children. The test (using the Shimizu protocol) was conducted in patients with some evidence of LQTS but in whom clinical and management decisions were challenging (n = 41, age 9.6 ± 3.9 years, 19 female). LQT1, LQT2, and negative responses to epinephrine were obtained in 16, 5, and 20 subjects, respectively. LQTS gene positivity was obtained in two subjects. Beta-blocker therapy was started in all subjects with a positive epinephrine response (n = 21) and in some negative responders because of their strong LQTS phenotype (n = 10). No therapy was given to the subset with less convincing features of LQTS who had also responded negatively to epinephrine (n = 10). Follow-up for 3.0 ± 2 years was uneventful in both management groups. Due to the discordance with genotyping, the epinephrine test cannot be used to diagnose genotype-positive LQTS but when used in combination with phenotype assessment and genetic screening, it could enable better management decisions

Socioeconomic hardship, uncertainty about the future, and adolescent mental wellbeing over a year during the COVID-19 pandemic

Socioeconomic vulnerabilities put adolescents at risk for mental wellbeing issues, also in times of a pandemic. In the present longitudinal online survey study, we explored changes in mental wellbeing (i.e., mood and life satisfaction) during the COVID-19 pandemic. Second, we examined how socioeconomic hardship in online home schooling predicted adolescents’ mental wellbeing 1 year later. Third, we tested whether this relation was mediated by feelings of uncertainty about the future. Fourth, we tested whether this relation was moderated (in terms of a protective factor) by self-efficacy. In total, 177 Dutch-speaking adolescents aged 10–18 years (Mage = 15.64, SDage = 1.72, 79% females) participated in all three 6-month separated waves (T1 = May 2020, T2 = November 2020, and T3 = May 2021). Mood results demonstrated that feelings of vigor decreased between T1 and T2, and feelings of tension and depression increased between T1, T2, and T3. Socioeconomic hardship in online home schooling in the early phase of the pandemic was negatively associated with both baseline mental wellbeing and 1 year later. Socioeconomic hardship at T1 predicted higher feelings of future uncertainty at T2, and higher levels of future uncertainty were associated with lower feelings of vigor, and higher feelings of tension and depression at T3. However, we found no evidence for mediation or moderation effects. In conclusion, the present findings illustrate the complexity of disentangling the adverse effects of socioeconomic hardship on adolescent mental wellbeing

How can care settings for people with intellectual disabilities embed health promotion?

Background: People with intellectual disabilities (ID) depend on their environment to live healthily. Asset-based health promotion enhances a settings’ health-promoting capacity starting with identifying protective or promotive factors that sustain health. Method: This inclusive mixed-methods study used group sessions to generate and rank ideas on assets supporting healthy nutrition and physical activity in Dutch intellectual disability care settings. Participants included people with moderate intellectual disabilities and family and care professionals of people with severe/profound intellectual disabilities. Results: Fifty-one participants identified 185 assets in group sessions. They include the following: (i) the social network and ways “people” can support, (ii) assets in/around “places,” and person–environment fit, and (iii) “preconditions”: health care, prevention, budget, and policy. Conclusion: This inclusive research provides a user perspective on assets in the living environment supporting healthy living. This gives insight in contextual factors needed for development and sustainable embedment of health promotion in the systems of intellectual disability support settings