Background: Web-based patient education materials (PEMs) are frequently written above the recommended reading level in North America. Poor PEM readability limits the accessibility of medical information for individuals with average literacy levels or lower. Pediatric hospital and association websites have not only been shown to be a preferred source of information among caregivers but have also become a necessity during the COVID-19 pandemic. The readability of Canadian pediatric association websites has not yet been assessed. Objective: The aim of this study is to determine if the content of PEMs from Canadian pediatric associations is written at a reading level that the majority of Canadians can understand. Methods: A total of 258 PEMs were extracted from 10 Canadian pediatric associations and evaluated for their reading level using 10 validated readability scales. The PEMs underwent a difficult word analysis and comparisons between PEMs from different associations were conducted. Results: Web-based PEMs were identified from 3 pediatric association websites, where the reading level (calculated as a grade level) was found to be an average of 8.8 (SD 1.8) for the Caring for Kids website, 9.5 (SD 2.2) for the Pediatric Endocrine Group website, and 13.1 (SD 2.1) for the Atlantic Pediatric Society website. The difficult word analysis identified that 19.9% (SD 6.6%) of words were unfamiliar, with 13.3% (SD 5.3%) and 31.9% (SD 6.1%) of words being considered complex (≥3 syllables) and long (≥6 letters), respectively. Conclusions: The web-based PEMs were found to be written above the recommended seventh-grade reading level for Canadians. Consideration should be made to create PEMs at an appropriate reading level for both patients and their caregivers to encourage health literacy and ultimately promote preventative health behaviors and improve child health outcomes.

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.

Disorders of developmental delay can occur from pathogenic variants in genes responsible for epigenetic regulation. Heterozygous and biallelic pathogenic variants in TET3 have recently been described in TET3‐related Beck–Fahrner syndrome (TET3‐BEFAHRS), representing an autosomal dominant disorder with variable expressivity. Typical features include intellectual disability and developmental delay. Patients can also present with facial dysmorphism, seizure disorder, ophthalmic findings, and other neurobehavioral features. As the condition has recently been described and few patients have been reported in literature, the full scope of the phenotypic spectrum and approaches to identify them are still emerging. We report an individual meeting the criteria for TET3‐BEFAHRS confirmed through clinical, genetic, and DNA methylation episignature analysis, who uniquely presents with bilateral chorioretinal and unilateral right iris colobomata. This case suggests a broader ophthalmic phenotype to TET3‐BEFAHRS and demonstrates the utility of episignatures for the diagnosis of Mendelian disorders of epigenetic machinery.

High‐dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variants have been implicated, the cumulative impact of genetic variation within relevant biological pathways remains unexplored. We evaluated single nucleotide polymorphisms across 18 pathways previously identified as relevant to mucositis in 278 pediatric patients with acute lymphoblastic leukemia from six academic health centers across Canada. Pathway enrichment was assessed using the Joint Association of Genetic variants tool, and a predictive model was developed using XGBoost, a supervised machine learning algorithm based on gradient‐boosted decision trees. Pathway enrichment identified significant associations in IL6 ( P = 0.04) and WNT/β‐catenin ( P = 0.048) signaling pathways. The predictive model (area under the curve [AUC] = 0.76) highlighted single nucleotide polymorphisms associated with inflammation‐ and mucosa‐related genes, including PRKCD , IL17B , MAST3 , and CAPN9 , with both risk and protective effects. Model performance dropped by 0.15 in AUC (from 0.76 to 0.61) after removing single nucleotide polymorphism features, underscoring their predictive value. This pathway‐informed approach identifies genetic contributors to methotrexate‐induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment‐limiting mucositis in pediatric oncology.

Background: Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitors genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared to TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected. Methods: We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant. Results: Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules, and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3 - diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4 - diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis. Conclusions: This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur. Crown Copyright (c) 2024 Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.