Reducing Commercial Tobacco Sales to Youth On and Around California Tribal Reservations with a Reward and Reminder Retail Intervention.

INTRODUCTION: High prevalence of commercial tobacco product (CTP) use among American Indian and Alaska Native (AI/AN) youth is a public health crisis. A multi-level Tribal-community-based participatory research project under Tribal public health authority implemented a retailer-focused intervention to reduce AI/AN youth CTP use. METHODS: We sought resolutions in support of a retailer-focused CTP intervention from Tribal Nations organized by a tribally-directed research program. We identified tobacco retail outlets operating on and within 5 miles of 9 Tribal reservations, and CTP products sold at these outlets. We conducted a four-wave Reward and Reminder intervention with apparent minor buyers. Clerks who complied with the law received a modest reward and commendation in social media posts to the local Tribal communities, while clerks who sold without age verification were reminded of the laws. RESULTS: Of 18 retail outlets selling CTP, 8 sold e-cigarettes, and all sold combustible cigarettes. The Reward and Reminder intervention showed an approximate 25% reduction in sales of CTP to apparent minors, with a 33% baseline CTP sales rate without age verification and an 8% intervention CTP sales rate without age verification. CONCLUSIONS: The intervention increased awareness of laws prohibiting CTP sales to minors and mandating age verification for young adults seeking to buy CTP. The intervention, which had support from all governing Tribal Nations, builds the evidence base of effective practices which Tribal public health authorities may utilize to reduce youth access to CTP on and around Tribal reservations. IMPLICATIONS: Sovereign Tribes have authority over commercial businesses operating on their lands. Tobacco 21 laws aiming to restrict commercial tobacco availability to youth are supported by Tribes. A retailer intervention in which apparent minors attempt commercial tobacco purchases can offer accountability feedback to retailers both on and near Tribal reservations. Obtaining Tribal support and publicizing the interventions helps mobilize Tribal communities to support commercial tobacco prevention and promote healthy youth.

Significant improvement of psychotic symptoms in treatment-resistant schizophrenia with clozapine in an adolescent with SHINE syndrome: a case report.

This report highlights a rare single-gene cause of early-onset, treatment-resistant schizophrenia, and its unique responsiveness to clozapine therapy. This case describes a pediatric female who was diagnosed with early-onset schizophrenia and catatonia in her early adolescence, and was later found to have DLG4-related synaptopathy, also known as SHINE syndrome. SHINE syndrome is a rare neurodevelopmental disorder caused by dysfunction of the postsynaptic density protein-95 (PSD-95), encoded by the DLG4 gene. After failing three antipsychotic drug treatments, the patient was started on clozapine, which resulted in significant improvements in positive and negative symptoms. This case illustrates the impact of clozapine in treatment-resistant early-onset psychosis and exemplifies practical implications for genetic testing in early-onset schizophrenia.

Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association.

DM catalyzes the exchange of peptides bound to Class II major histocompatibility complex (MHC) molecules. Because the dissociation and association components of the overall reaction are difficult to separate, a detailed mechanism of DM catalysis has long resisted elucidation. UV irradiation of DR molecules loaded with a photocleavable peptide (caged Class II MHC molecules) enabled synchronous and verifiable evacuation of the peptide-binding groove and tracking of early binding events in real time by fluorescence polarization. Empty DR molecules generated by photocleavage rapidly bound peptide but quickly resolved into species with substantially slower binding kinetics. DM formed a complex with empty DR molecules that bound peptide with even faster kinetics than empty DR molecules just having lost their peptide cargo. Mathematical models demonstrate that the peptide association rate of DR molecules is substantially higher in the presence of DM. We therefore unequivocally establish that DM contributes directly to peptide association through formation of a peptide-loading complex between DM and empty Class II MHC. This complex rapidly acquires a peptide analogous to the MHC class I peptide-loading complex.