Multidisciplinary Management of Rett Syndrome: Twenty Years' Experience.

Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome. We aim to improve awareness and understanding of Rett syndrome amongst pediatricians, pediatric subspecialists and allied health professionals to enable early diagnosis and a streamlined enrolment approach for future clinical trials. Rett syndrome, a complex X-linked condition, affecting mainly females, is due to pathogenic variants of the MECP2 gene in most affected individuals. The Rett syndrome Multidisciplinary Management clinic at The Children's Hospital at Westmead, Sydney, Australia, was established in 2000. This retrospective analysis of individuals who attended the clinic from 2000 to 2020 was performed to identify the incidence and predicted age of onset of Rett syndrome related comorbidities, disease progression and to review management principles. Data collected included age of Rett syndrome diagnosis, MECP2 genotype, clinical features and medical comorbidities, such as sleep disturbance, seizures, breathing irregularities, scoliosis, mobility, hand stereotypies, hand function, constipation, feeding ability, use of gastrostomy, communication skills, QTc prolongation, anthropometry, and bruxism. Analysis of 103 girls who fulfilled the clinical diagnostic criteria for classical Rett syndrome with a pathogenic variant of the MECP2 gene showed a median age of diagnosis of 3 years. The most frequent MECP2 variant was c.502 C>T.

Near-infrared emitting dual-stimuli-responsive carbon dots from endogenous bile pigments.

Carbon dots are biocompatible nanoparticles suitable for a variety of biomedical applications. Careful selection of carbon dot precursors and surface modification techniques has allowed for the development of carbon dots with strong near-infrared fluorescence emission. However, carbon dots that provide strong fluorescence contrast would prove even more useful if they were also responsive to stimuli. In this work, endogenous bile pigments bilirubin (BR) and biliverdin (BV) were used for the first time to synthesize stimuli-responsive carbon dots (BR-CDots and BV-CDots respectively). The precursor choice lends these carbon dots spectroscopic characteristics that are enzyme-responsive and pH-responsive without the need for surface modifications post-synthesis. Both BV- and BR-CDots are water-dispersible and provide fluorescence contrast, while retaining the stimuli-responsive behaviors intrinsic to their precursors. Nanoparticle Tracking Analysis revealed that the hydrodynamic size of the BR-CDots and BV-CDots decreased with exposure to bilirubin oxidase and biliverdin reductase, respectively, indicating potential enzyme-responsive degradation of the carbon dots. Fluorescence spectroscopic data demonstrate that both BR-CDots and BV-CDots exhibit changes in their fluorescence spectra in response to changes in pH, indicating that these carbon dots have potential applications in pH sensing. In addition, BR-CDots are biocompatible and provide near-infrared fluorescence emission when excited with light at wavelengths of 600 nm or higher. This work demonstrates the use of rationally selected carbon sources for obtaining near-infrared fluorescence and stimuli-responsive behavior in carbon dots that also provide strong fluorescence contrast.