A Survey of Demographics, Symptom Course, Family History, and Barriers to Treatment in Children with Pediatric Acute-Onset Neuropsychiatric Disorders and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections.

Few large-scale studies of pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) have been conducted, and thus demographic data on these conditions are limited. The current study describes comorbid medical and psychiatric conditions in a self-referred cohort of children with PANS/PANDAS, along with treatment history, barriers to treatment, family medical and psychiatric history, and perceived caregiver burden in these conditions. A total of 441 primary caregivers of patients with infection-triggered PANS/PANDAS under the age of 18 were included in this online anonymous survey, reporting on a total of 490 children (due to some caregivers reporting multiple children in the family with PANS/PANDAS).

The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy.

The current study assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS, a condition characterized by sudden-onset obsessive-compulsive, tic, or restrictive eating symptoms following infection. We conducted an anonymous survey between February and June 2021 of 254 self-reported caregivers of minors with PANS/PANDAS. Caregivers answered questions regarding PANS/PANDAS symptoms, telehealth care, and intention to vaccinate their child against COVID-19.

Design, Synthesis, and Evaluation of Thienodiazepine Derivatives as Positron Emission Tomography Imaging Probes for Bromodomain and Extra-Terminal Domain Family Proteins.

To better understand the role of bromodomain and extra-terminal domain (BET) proteins in epigenetic mechanisms, we developed a series of thienodiazepine-based derivatives and identified two compounds, and , as potent BET inhibitors. Further pharmacokinetic studies and analysis of metabolic stability of revealed excellent brain penetration and reasonable metabolic stability. Compounds and were radiolabeled with fluorine-18 in two steps and utilized in positron emission tomography (PET) imaging studies in mice.

Synthesis and Characterization of a Positron Emission Tomography Imaging Probe Selectively Targeting the Second Bromodomain of Bromodomain Protein BRD4.

Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target.

Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome.

We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain.