Andrea Markkula

Background: Internalising problems and engagement issues are prevalent among preschool children but often go undetected and untreated. There is a notable lack of longitudinal studies examining their long-term impact on functional outcomes and disability. Further knowledge in this area could support the identification of children at risk and inform the development of targeted interventions. Aim: This study aimed to investigate the longitudinal associations between emotional problems and low engagement on functional outcomes, while controlling for potential confounding variables. Method: Preschool teachers assessed a representative cohort of 617 Swedish preschool children (317 boys and 300 girls, aged 24–71 months). The study consisted of three assessment waves. At baseline (Wave 1), teachers provided ratings of children’s emotional problems, engagement levels, and functional outcomes. Functional outcomes were then reassessed at Waves 2 and 3. Baseline emotional problems and low engagement were used to define risk groups. Associations between these baseline risk groups and functional outcomes across waves were analysed using Generalised Linear Mixed Models (GLMMs). Results: In an interaction model, children with both emotional problems and low engagement exhibited the greatest functional outcome improvement over time (b = 0.063; 95% CI [0.038, 0.088] p < 0.001), suggesting potential for developmental catch-up. In a model excluding interaction terms, both emotional problems and low engagement were associated with lower ratings on functional outcomes. Additionally, increasing age, being female, and being a native speaker were associated with higher functional outcomes.

Supplementary Fig. S1. Effect by caffeine or caffeic acid on apoptotic mediators

Supplementary Fig. S1. Effect by caffeine or caffeic acid on apoptotic mediators

Multiple clinical trials investigate statins’ effects in breast cancer. The ABCB1 genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, ABCB1 genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, ABCB1 C3435T genotype, and HMGCR expression in relation to outcome were analyzed in 985 primary breast cancer patients from a population-based prospective cohort in Sweden from 2002-2012. Preoperative statin use (n=80) was not associated with ABCB1 C3435T genotype (n=576), HMGCR expression (n=848), or clinical outcomes. ABCB1 C3435T TT-carriers had lower risk of breast cancer events than any C-carriers (adjusted hazard ratio (HRadj) 0.74; 95%CI 0.49, 1.12), but only in non-statin users (Pinteraction=0.042). Statin users with TT genotype had higher risk of distant metastasis (HRadj 4.37; 95%CI 1.20, 15.91; Pinteraction=0.009) and shorter overall survival than other patients (HRadj 3.77; 95%CI 1.37, 10.39; Pinteraction=0.019). In conclusion, there were nominally significant interactions between ABCB1 genotype and preoperative statin use on clinical outcomes, while preoperative statin use was not associated with outcomes. Since this is an exploratory study of the impact of the ABCB1 genotype in relation to statin use and clinical outcomes in the breast cancer setting, the results should be interpreted with caution and warrant replication in an independent cohort, preferably in a randomized setting. Since statin use is common in breast cancer patients, it would be of interest to further elucidate the clinical impact of the ABCB1 genotype in breast cancer.