Progress After Placement

The chapter explores the progress made by the 93 adoptees in the core follow-up sample in terms of physical and mental health and education from the time they entered their adoptive homes until they were followed up, on average 18 years later. It draws on data collected through responses to an online survey concerning 93 adoptees (44% of the cohort) completed at follow-up, and interviews focusing on 24 adult adoptees. On entering their placements, 40% of adoptees were developmentally delayed; 13% had poor physical health; 38% were in poor mental health. Emotional and behavioural problems affected their academic progress; 76% required specialist help. After placement, 74% improved in physical health, 66% in mental health and 68% in academic performance. The challenges faced by adoptive parents provide a powerful case for careful preparation and long-term post-adoption support.

P.100 A Retrospective Study of Alberta Emergency Room Utilization by Pediatric Epilepsy Patients

Background: Epilepsy, a common neurologic condition, instigates a large number of emergency room (ER) visits annually. This project aims to retrospectively review the patterns and characteristics of Alberta ER visits by pediatric epilepsy patients. Methods: Methods: Alberta Health administrative databases, including the Inpatient Discharge Abstract Database, the National Ambulatory Care Reporting System, Diagnostic Imaging and Medical Laboratory, were used to identify ER utilization patterns among children with epilepsy in Alberta, Canada between 2012–2018. Results: Results: Of 5,419 pediatric epilepsy ER patients between 2012–2018 in Alberta, 59% were developmentally delayed children. Children in this particular group, when compared to developmentally normal children with epilepsy, had the following characteristics: they were significantly more likely to utilize ERs in children’s hospitals versus other hospitals; they presented at a significantly younger age; they had a significantly longer length of stay; they had higher triage scores; they were subjected to significantly more investigations; and they had significantly more hospital admissions for epilepsy. Conclusions: Discussion: This novel Alberta-wide study of resource utilization of pediatric epilepsy patients shows that developmentally delayed children with epilepsy use significantly higher resources compared to developmentally normal children with epilepsy. Whether this is justified or not requires further study.

Comparative Hessian Fly Larval Transcriptomics Provides Novel Insight into Host and Nonhost Resistance

The Hessian fly is a destructive pest of wheat. Employing additional molecular strategies can complement wheat’s native insect resistance. However, this requires functional characterization of Hessian-fly-responsive genes, which is challenging because of wheat genome complexity. The diploid Brachypodium distachyon (Bd) exhibits nonhost resistance to Hessian fly and displays phenotypic/molecular responses intermediate between resistant and susceptible host wheat, offering a surrogate genome for gene characterization. Here, we compared the transcriptomes of Biotype L larvae residing on resistant/susceptible wheat, and nonhost Bd plants. Larvae from susceptible wheat and nonhost Bd plants revealed similar molecular responses that were distinct from avirulent larval responses on resistant wheat. Secreted salivary gland proteins were strongly up-regulated in all larvae. Genes from various biological pathways and molecular processes were up-regulated in larvae from both susceptible wheat and nonhost Bd plants. However, Bd larval expression levels were intermediate between larvae from susceptible and resistant wheat. Most genes were down-regulated or unchanged in avirulent larvae, correlating with their inability to establish feeding sites and dying within 4–5 days after egg-hatch. Decreased gene expression in Bd larvae, compared to ones on susceptible wheat, potentially led to developmentally delayed 2nd-instars, followed by eventually succumbing to nonhost resistance defense mechanisms.

Maintenance Electroconvulsive Therapy Is an Essential Medical Treatment for Patients With Catatonia: A COVID-19 Related Experience

Aim: Describe naturalistic clinical course over 14 weeks in a mixed adolescent and a young-adult patient group diagnosed with developmental delays and catatonia, when the frequency of maintenance electroconvulsive therapy (M-ECT) was reduced secondary to 2020 COVID-19 pandemic restrictions.Methods: Participants were diagnosed with catatonia, and were receiving care in a specialized clinic. They (n = 9), F = 5, and M = 4, ranged in age from 16 to 21 years; ECT frequency was reduced at end of March 2020 due to institutional restrictions. Two parents/caregivers elected to discontinue ECT due to concern for COVID-19 transmission. Majority (n = 8) were developmentally delayed with some degree of intellectual disability (ID). Observable symptoms were rated on a three point scale during virtual visits.Results: All cases experienced clinically significant decline. Worsening of motor symptoms (agitation, aggression, slowness, repetitive self-injury, stereotypies, speech deficits) emerged within the first 3 weeks, persisted over the 14 week observation period and were more frequent than neurovegetative symptoms (appetite, incontinence, sleep). Four participants deteriorated requiring rehospitalization, and 2 among these 4 needed a gastrostomy feeding tube.Conclusion: Moderate and severe symptoms became apparent in all 9 cases during the observation period; medication adjustments were ineffective; resuming M-ECT at each participant's baseline schedule, usually by week 7, resulted in progressive improvement in some cases but the improvement was insufficient to prevent re-hospitalization in 4 cases. In summary, rapid deterioration was noted when M-ECT was acutely reduced in the setting of COVID-19 related restrictions.

Performance of Cornell Assessment of Pediatric Delirium Scale in Mechanically Ventilated Children

Accuracy of delirium diagnosis in mechanically ventilated children is often limited by their varying developmental abilities. The purpose of this study was to examine the performance of the Cornell Assessment of Pediatric Delirium (CAPD) scale in these patients. This is a single-center prospective observational study of patients requiring sedation and mechanical ventilation for 2 days or more. CAPD scale was implemented in our unit for delirium screening. Each CAPD assessment was accompanied by a physician assessment using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Sensitivity analysis was performed to determine the best cut-off score in our target population. We also evaluated ways to improve the accuracy of this scale in patients with and without developmental delay. A total of 837 paired assessments were performed. Prevalence of delirium was 19%. Overall, CAPD score ≥ 9 had sensitivity of 81.8% and specificity of 44.8%. Among typically developed patients, the sensitivity and specificity were 76.7 and 65.4%, respectively, whereas specificity was only 16.5% for developmentally delayed patients. The best cut-off value for CAPD was 9 for typically developed children and 17 for those with developmental delay (sensitivity 74.4%, specificity 63.2%). Some CAPD questions do not apply to patients with sensory and neurocognitive deficits; upon excluding those questions, the best cut-off values were 5 for typically developed and 6 for developmentally delayed children. In mechanically ventilated patients with developmental delay, CAPD ≥ 9 led to a high false-positive rate. This emphasizes the need for either a different cut-off score or development of a delirium scale specific to this patient population.

EHMT2 Controls Transcriptional Noise and the Developmental Switch after Gastrulation in the Mouse Embryo

Embryos that carry zygotic or parental mutations in Ehmt2, the gene encoding the main euchromatic histone H3K9 methyltransferase, EHMT2, exhibit variable developmental delay. We asked the question whether the delayed embryo is different transcriptionally from the normally developing embryo when they reach the same developmental stage. We collected embryos carrying a series of genetic deficiencies in the Ehmt2 gene and performed total RNA sequencing of somite stage-matched individual embryos. We applied novel four-way comparisons to detect differences between normal versus deficient embryos, and between 12-somite and 6-somite embryos. Importantly, we also identified developmental changes in transcription that only occur during the development of the normal embryo. We found that at the 6-somite stage, gastrulation-specific genes were not precisely turned off in the Ehmt2-/- embryos, and genes involved in organ growth, connective tissue development, striated muscle development, muscle differentiation, and cartilage development were not precisely switched on in the Ehmt2-/- embryos. Zygotic EHMT2 reduced transcriptional variation of developmental switch genes and at some repeat elements at the six-somite stage embryos. Maternal EHMT2-mutant embryos also displayed great transcriptional variation consistent with their variable survival, but transcription was normal in developmentally delayed parental haploinsufficient embryos, consistent with their good prospects. Global profiling of transposable elements in the embryo revealed that specific repeat classes responded to EHMT2. DNA methylation was specifically targeted by EHMT2 to LTR repeats, mostly ERVKs. Long noncoding transcripts initiated from those misregulated driver repeats in Ehmt2-/- embryos, and extended to several hundred kilobases, encompassing a multitude of additional, similarly misexpressed passenger repeats. These findings establish EHMT2 as an important regulator of the transition between gastrulation programs and organ specification programs and of variability.

FBXO11-Mediated Proteolysis of BAHD1 Relieves PRC2-dependent Transcriptional Repression in Erythropoiesis

The histone mark H3K27me3 and its reader/writer Polycomb repressive complex 2 (PRC2) mediate widespread transcriptional repression in stem and progenitor cells. Mechanisms that regulate this activity are critical for hematopoietic development but poorly understood. Here we show that the E3 ubiquitin ligase FBXO11 relieves PRC2-mediated repression during erythroid maturation by targeting its newly identified substrate BAHD1, an H3K27me3 reader that recruits transcriptional co-repressors. Erythroblasts lacking FBXO11 are developmentally delayed, with reduced expression of maturation-associated genes, most of which harbor bivalent histone marks (activating H3K4me3 and repressive H3K27me3), bind BAHD1, and fail to recruit the erythroid transcription factor GATA1. The BAHD1 complex interacts physically with PRC2 and depletion of either component restores FBXO11-deficient erythroid gene expression. Our studies identify BAHD1 as a novel effector of PRC2-mediated repression and reveal how a single E3 ubiquitin ligase eliminates PRC2 repression at developmentally poised bivalent genes during erythropoiesis.