Trajectories of school refusal: sequence analysis using retrospective parent reports.

School refusal (SR) is a form of school attendance problem (SAP) that requires specific mental health care. Despite improvements in the definition of SAPs, the course of SR is not well characterized. To explore three-year patterns of SR course in children, as reported by their parents, we deployed an anonymous web-based survey. We defined SR onset as the absence of ≥ 2 school weeks during one academic year, combined with emotional distress. We defined standard SR trajectories using sequence analysis of parents' recollection of three consecutive years of school attendance. We obtained 1970 responses, 1328 (67%) completed by a parent and meeting the definition of SR. Of these, 729 (55%) responses included three years of school attendance recollection. We identified five prototypical trajectories of SR: two profiles for children: beaded absences (n = 272), and rapid recovery (n = 132); and three for adolescents: prolonged recovery (n = 93), gradual decline (n = 89), and rapid decline (n = 143). We found five distinct trajectories of retrospective recall of SR course. Through pattern recognition, this typology could help with timely identification of SR and implementation of evidence-based interventions to optimize outcomes. Prospective replication of these findings and their field application is warranted.

Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole.

Exposure to endocrine-disrupting chemicals (EDCs) during development may cause reproductive disorders in women. Although female reproductive endpoints are assessed in rodent toxicity studies, a concern is that typical endpoints are not sensitive enough to detect chemicals of concern to human health. If so, measured endpoints must be improved or new biomarkers of effects included. Herein, we have characterized the dynamic transcriptional landscape of developing rat ovaries exposed to two well-known EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ), by 3' RNA sequencing. Rats were orally exposed from day 7 of gestation until birth, and from postnatal day 1 until days 6, 14 or 22. Three exposure doses for each chemical were used: 3, 6 and 12 µg/kg bw/day of DES; 3, 6, 12 mg/kg bw/day of KTZ. The transcriptome changed dynamically during perinatal development in control ovaries, with 1137 differentially expressed genes (DEGs) partitioned into 3 broad expression patterns. A cross-species deconvolution strategy based on a mouse ovary developmental cell atlas was used to map any changes to ovarian cellularity across the perinatal period to allow for characterization of actual changes to gene transcript levels. A total of 184 DEGs were observed across dose groups and developmental stages in DES-exposed ovaries, and 111 DEGs in KTZ-exposed ovaries across dose groups and developmental stages. Based on our analyses, we have identified new candidate biomarkers for female reproductive toxicity induced by EDC, including Kcne2, Calb2 and Insl3.