Annual Research Review: Health anxiety in children and adolescents-developmental aspects and cross-generational influences.

Health anxiety involves excessive worries about one's health along with beliefs one has an illness or may contract a serious disease. Concerning evidence suggests that health anxiety is on the rise in society, possibly further fueled by the COVID-19 pandemic. Recent classification systems acknowledge that impairing health-related worries and beliefs can emerge in early childhood with significant levels of symptoms persisting throughout childhood, and possibly continuous with diagnostic considerations in adulthood. This narrative review summarizes recent research advances in health anxiety in children and adolescents, focusing on various developmental aspects of health anxiety and related concepts in youths. Findings suggest that health anxiety symptoms in young age groups are associated with impairment, distress, and increased healthcare use, as well as substantial comorbidity with mainly other emotional problems and disorders. Furthermore, longitudinal studies suggest that childhood health anxiety can persist across adolescence, perhaps with links to chronic courses in adulthood. The growing literature was further reviewed, thus extending our understanding of early risk factors, including the potential role of exposure to serious illness and transgenerational transmission of health anxiety. Learning more about developmental trajectories will be highly relevant to inform strategies for early detection and prevention. While modified cognitive behavioral therapies in adults are successful in treating health anxiety, specific interventions have not yet been tested in youths. Given substantial overlaps with other psychopathology, it could be important to develop and explore more transdiagnostic and scalable approaches that take advantage of common factors in psychotherapy, while also including a wider perspective on potential familiar maladaptive illness cognitions and behaviors.

Development of Noncovalent Small-Molecule Keap1-Nrf2 Inhibitors by Fragment-Based Drug Discovery.

Targeting the protein-protein interaction (PPI) between the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its repressor, Kelch-like ECH-associated protein 1 (Keap1), constitutes a promising strategy for treating diseases involving oxidative stress and inflammation. Here, a fragment-based drug discovery (FBDD) campaign resulted in novel, high-affinity (Ki = 280 nM), and cell-active noncovalent small-molecule Keap1-Nrf2 PPI inhibitors. We screened 2500 fragments using orthogonal assays─fluorescence polarization (FP), thermal shift assay (TSA), and surface plasmon resonance (SPR)─and validated the hits by saturation transfer difference (STD) NMR, leading to 28 high-priority hits. Thirteen co-structures showed fragments binding mainly in the P4 and P5 subpockets of Keap1's Kelch domain, and three fluorenone-based fragments featuring a novel binding mode were optimized by structure-based drug discovery. We thereby disclose several fragment hits, including their binding modes, and show how FBDD can be performed to find new small-molecule Keap1-Nrf2 PPI inhibitors.

The association between psychosocial interventions and fertility treatment outcome: A systematic review and meta-analysis.

OBJECTIVE: Does psychosocial intervention affect pregnancy outcomes in women and couples undergoing assisted reproductive technology (ART) treatment?. DESIGN: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) evaluating the efficacy of psychosocial intervention on pregnancy outcomes in women and couples undergoing ART treatment. The primary outcome was Pregnancy Rates. Secondary outcomes were Live Birth Rate (LBR) and Abortion Rate (AR). MATERIALS AND METHODS: Databases searched were Pubmed, PsycINFO, Embase, CINAHL and The Cochrane Library. 1439 records were screened, 15 were eligible and included in the meta-analyses (N = 2434). Data was extracted using the Covidence software. Effect sizes were reported as relative risks with 95% confidence-intervals and p-values. RESULTS: A positive association was found between psychosocial intervention and pregnancy rates (RR = 1.12 CI=(1.01;1.24), p = 0.033). Long-duration interventions and mind-body intervention types were found to be associated with increased pregnancy rates (RR 1.21, CI= (1.04;1.43), p = 0.017) and (RR = 1.25, CI= (1.00;1.55), p = 0.046) respectively. Q and I2tests suggested no to low heterogeneity. Funnel plots, Trim and Fill analyses and Fail-safe numbers were applied to adjust for possible publication bias. CONCLUSIONS: Our findings suggest a positive association between psychosocial interventions, particularly long-duration interventions, and pregnancy rate in infertile women and couples in ART treatment. The findings are in line with findings from other reviews and meta-analyses exploring the same topic. More good quality RCTs need to be performed to increase the quality of guidance for infertile women and couples. The effect of psychosocial interventions on LBR and AR remain to be examined.