Patient-Reported oral health outcome measurement for children and adolescents

BACKGROUND: Oral health is an important component of daily functioning and well-being. A comprehensive patient-reported oral health measure is needed to gauge the impact of oral health status on children and adolescents. This study aims to develop oral health item banks and associated short-form surveys for children and adolescents 2–17 year olds. METHODS: Using children and adolescents, ages 2–17 years, selected from diverse dental sites in Greater Los Angeles Area, we propose to develop state-of-the-science methods to create oral health item banks to effectively measure oral health outcomes for children and adolescents. Methods include a literature review of existing measures, focus groups, cognitive interviews, drafting and field testing of survey items, and evaluation of the psychometric properties of the measures. RESULTS: Based on the systematic literature search and focus groups, we identified core (physical health, mental health, and social function domains) and peripheral (e.g., need and access) oral health domains. We then drafted survey items and revised them based on 66 cognitive interviews (27 children/adolescents and 39 parents) with 39 families. The revised items will be administered in a field test of 500 children and adolescents ages 2–17, and their parents. CONCLUSIONS: The qualitative methods used in the initial phases of the project (focus group and cognitive interviews) are the initial steps in the development of oral health item banks and associated short-form surveys for children and adolescents. The oral health items can potentially be used to create effective computerized adaptive test and/or create ad hoc short forms targeting specific areas of oral health to survey large populations of children with much less cost compared with traditional clinical oral health examination

Balloon cells promote immune system activation in focal cortical dysplasia type 2b

AIMS: Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian target of rapamycin (mTOR) pathway. Histopathologically, FCD 2 is subdivided into FCD 2a and FCD 2b, the only discriminator being the presence of balloon cells (BCs) in FCD 2b. While pro‐epileptogenic immune system activation and inflammatory responses are commonly detected in both subtypes, it is unknown what contextual role BCs play. METHODS: The present study employed RNA sequencing of surgically resected brain tissue from FCD 2a (n = 11) and FCD 2b (n = 20) patients compared to autopsy control (n = 9) focusing on three immune system processes: adaptive immunity, innate immunity and cytokine production. This analysis was followed by immunohistochemistry on a clinically well‐characterised FCD 2 cohort. RESULTS: Differential expression analysis revealed stronger expression of components of innate immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, particularly complement activation and antigen presentation. Immunohistochemical analysis confirmed these findings, with strong expression of leukocyte antigen I and II in FCD 2b as compared to FCD 2a. Moreover, T‐lymphocyte tissue infiltration was elevated in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in subcortical white matter. Lastly, antigen presentation was strongly correlated with BC load in FCD 2b lesions. CONCLUSION: We conclude that, next to mutation‐driven mTOR activation and seizure activity, BCs are crucial drivers of inflammation in FCD 2b. Our findings indicate that therapies targeting inflammation may be beneficial in FCD 2b

microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus

The ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7R-gated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7(−/−) mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain