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Phytochemical investigation of the leaf extract of Uvaria grandiflora Roxb. ex Hornem led to the isolation and identification of two new highly oxygenated cyclohexenes, uvariagrandols A (1) and B (2), together with seven known compounds (3–9). Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. The (1S,2S,3R,6S) absolute configuration of uvariagrandols A and B was established by the comparison of the experimental and calculated electronic circular dichroism (ECD). (+)-Grandifloracin (9) displayed cytotoxicity against SW480 and K562 cell lines with IC50 values of 154.9 and 60.9 μM, respectively. 6-Methoxyzeylenol (5) had α-glucosidase inhibitory activity with the IC50 value of 34.1 μM.

Aim: This study examines trends in paracetamol overdoses among Danish adolescents during and following the COVID-19 pandemic., Methods: A retrospective observational study was conducted using data from the national databases, covering all paediatric departments in Denmark from January 2016 to December 2023. Patients between 10 and 19 years of age diagnosed with paracetamol overdose were stratified by sex, age and number of hospital admissions. As the dataset covers the entire population, observed values reflect true parameters. A one-sample t-test compared post-COVID-19 values to the pre-COVID-19 mean., Results: A total of 4.448 patients accounted for 5.794 hospital admissions due to paracetamol overdoses, with a majority being girls. During the second year of the pandemic (2021), a rise in overdose cases (26.5%) and hospital admissions (30.3%) was observed, especially among girls. The average number of admissions per patient increased, indicating repeated self-harm attempts. Cases of severe overdoses leading to acute liver failure increased at Rigshospitalet. These trends reversed post-pandemic., Conclusion: The findings suggest an association between pandemic-related isolation and an increase in adolescent paracetamol overdoses. While rates began to normalise after restrictions were lifted, further research is needed to assess the long-term mental health impact of such restrictions., (© 2025 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and non-genetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Transition to adult care is a challenging and complex process for youth and emerging adults with chronic health and/or mental health conditions. Patient navigation has been proposed to improve care during transition, but previous studies have used single disease cohorts with a nonrandomized design., Objective: To compare the effectiveness of a patient navigator service to reduce emergency department (ED) use among adolescents and emerging adults with chronic health and/or mental health conditions undergoing transition to adult-oriented health care., Design, Setting, and Participants: This was a pragmatic, parallel-group, nonblinded randomized clinical trial design. Patients were followed up for a minimum 12 months and maximum 24 months after enrollment. The setting was the Canadian province of Alberta, with a population of 4.3 million inhabitants, having 3 tertiary care pediatric hospitals serving the entire population with universal health coverage. Participants included youth aged 16 to 21 years, followed up within a diverse array of chronic care clinics, expected to be transferred to adult care within 12 months, residing in Alberta, Canada., Interventions: A 1:1 allocation to either access to a personalized navigator, an experienced social worker within the health services environment, or usual care, for up to 24 months after randomization., Main Outcomes and Measures: All-cause ED visit rate while under observation., Results: A total of 335 participants were randomized over a period of 45 months, 164 (49.0%) to the intervention arm and 171 (51.0%) to usual care. After 1 patient withdrew, 334 participants (usual care: mean [SD] age, 17.8 [0.7] years; 99 female [57.9%]; intervention: mean [SD] age, 17.7 [0.6] years; 81 male [49.7%]) were included in the final data analysis. Among the participants, 131 (39.2%) resided in a rural location, and 126 (37.7%) had a self-reported mental health comorbidity during baseline assessment. We observed significant effect modification in the relationship between intervention and ED visits based on mental health comorbidity. Among those with a self-reported mental health condition, ED visit rates were lower in those with access to the navigator, but the association was not significant (adjusted incidence rate ratio [IRR] 0.75; 95% CI, 0.47-1.19). Among those with no mental health comorbidity, the corresponding adjusted IRR was 1.45 (95% CI, 0.95-2.20)., Conclusions and Relevance: In this randomized clinical trial, the navigator intervention was not associated with a significant reduction in ED visits among youth with chronic health conditions transitioning to adult care. The study did not accrue sufficient sample size to demonstrate a significant difference between groups should it exist., Trial Registration: ClinicalTrials.gov Identifier: NCT03342495.

Importance: Current upper-extremity therapies provide inconsistent outcomes for children with unilateral cerebral palsy. Noninvasive brain stimulation, specifically transcranial direct current stimulation, may enhance motor gains when combined with therapy., Objective: To determine whether the addition of neurostimulation to upper-extremity therapy enhances motor function in children with perinatal stroke and unilateral cerebral palsy., Design, Setting, and Participants: This multicenter, randomized, sham-controlled phase 3 trial was conducted from July 2017 through March 2023. Investigators, treating therapists, outcome assessors, parents, and participants were blinded to intervention allocation. The study took place at 3 tertiary care Canadian pediatric rehabilitation hospitals. From a population-based sample of children 6 to 18 years old with perinatal stroke and disabling unilateral cerebral palsy, 196 children were approached and 107 were excluded., Intervention: Participants were randomly assigned in permuted blocks of 2 (1:1) to receive daily sham or cathodal stimulation to the contralesional motor cortex during 10 days of high-dose, child-centered intensive upper-extremity therapy., Main Outcomes and Measures: The primary end points were changes from baseline to 6 months posttherapy in affected hand function and attainment of child-identified functional goals assessed by the Assisting Hand Assessment and Canadian Occupational Performance Measure. Safety was assessed, including any decrease in the function of either hand. Analysis was intention to treat., Results: Eighty-nine children were enrolled with 45 randomized to sham (62% male, 38% female; mean [SD] age, 10.7 [2.8] years) and 44 to stimulation (52% male, 48% female; mean [SD] age, 10.7 [2.1] years). Eighty-three participants had complete outcome data (42 sham, 41 stimulation). High proportions of children in both groups demonstrated significant functional gains sustained at 6 months (P < .001) with large effect size (Cohen d > 1). There were no differences between groups for mean (SD) change in hand function (5.2 [5.3] vs 4.6 [5.7]; P = .63) or goal attainment (3.0 [2.0] vs 3.6 [2.3]; P = .25). Procedures were safe and well tolerated with no serious adverse events., Conclusions and Relevance: In this study, results showed that patient-centered intensive motor learning programs could produce marked and sustained improvements in upper-extremity function in children with perinatal stroke and unilateral cerebral palsy. The addition of 1 milliampere contralesional motor cortex transcranial direct current stimulation did not improve outcomes compared with sham stimulation., Trial Registration: ClinicalTrials.gov Identifier: NCT03216837.