Shua Wong

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.The congenital disorder 22q11.2 deletion syndrome, characterized by a hemizygous deletion of 1.5-3 Mb on chromosome 22 at locus 11.2, is the most common microdeletion disorder and the second risk factor for schizophrenia. Nine of - 30 genes involved in 22qDS have the potential of disrupting mitochondrial metabolism. Deficits in bioenergetics during early postnatal brain development could set the basis for a disrupted neuronal metabolism or synaptic signaling, partly explaining the higher incidence in developmental and behavioral deficits in these individuals. Here, we investigated whether mitochondrial outcomes and metabolites from 22qDS children segregated with the altered dosage of one or several of these mitochondrial genes contributing to 22qDS etiology and/or morbidity. Plasma metabolomics, lymphocytic mitochondrial outcomes, and epigenetics were evaluated in samples from 11 22qDS children and 13 age- and sex-matched neurotypically developing controls. Metabolite differences between 22qDS children and controls reflected a shift from oxidative phosphorylation to glycolysis accompanied by an increase in reductive carboxylation of α-ketoglutarate. Altered metabolism in 22qDS reflected a critical role for the haploinsufficiency of the mitochondrial citrate transporter SLC25A1, further enhanced by HIF-1α, MYC, and metabolite controls. This comprehensive profiling served to clarify the biochemistry of this disease underlying its broad, complex phenotype.

Objectives. We conducted a dissemination and implementation study to translate an intervention protocol for Asian-language smokers froman efficacy trial into an effective and sustainable multistate service. Methods. Three state tobacco programs promoted a multistate cessation quitline to 3 Asian-language-speaking communities: Chinese, Korean, and Vietnamese. The California quitline provided counseling centrally to facilitate implementation. Threemore states joined the program during the study period. We assessed the provision of counseling, quitting outcomes, and dissemination of the program. Results. A total of 2004 smokers called for the service, with 88.3% opting for counseling. Among those opting for counseling, the 6-month abstinence rate was similar to results of the earlier efficacy trial. Conclusions. The intervention protocol, based on an efficacy trial, was successfully translated into amultistate service and further disseminated. This project paved theway for the establishment of a national quitline for Asian-language speakers, which serves as an important strategy to address disparities in access to care.