RESUMO
Gene expression is a critical component of brain physiology, but monitoring this expression in the living brain represents a major challenge. Here, we introduce a new paradigm called recovery of markers through insonation (REMIS) for noninvasive measurement of gene expression in the brain with cell type, spatial, and temporal specificity. Our approach relies on engineered protein markers that are produced in neurons but exit into the brain's interstitium. When ultrasound is applied to targeted brain regions, it opens the blood-brain barrier and releases these markers into the bloodstream. Once in blood, the markers can be readily detected using biochemical techniques. REMIS can noninvasively confirm gene delivery and measure endogenous signaling in specific brain sites through a simple insonation and a subsequent blood test. REMIS is reliable and demonstrated consistent improvement in recovery of markers from the brain into the blood. Overall, this work establishes a noninvasive, spatially specific method of monitoring gene delivery and endogenous signaling in the brain.
Assuntos
Barreira Hematoencefálica , Encéfalo , Transgenes , Animais , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Camundongos , Técnicas de Transferência de Genes , Expressão Gênica , HumanosRESUMO
Gene expression is a critical component of brain physiology and activity, but monitoring this expression in the living brain represents a significant challenge. Here, we introduce a new paradigm called Recovery of Markers through InSonation (REMIS) for noninvasive measurement of gene expression in the brain with cell-type, spatial, and temporal specificity. Our approach relies on engineered protein markers that are designed to be expressed in neurons and exit into the interstitium. By applying ultrasound to targeted brain regions, these markers are released into the bloodstream, where they can be readily detected using biochemical techniques. REMIS can noninvasively confirm gene delivery and measure endogenous signaling in specific brain sites through a simple insonation and a subsequent blood test. Using REMIS, we successfully measured chemogenetic induction of neuronal activity in ultrasound-tar-geted brain regions. REMIS recovery of markers is reliable and demonstrated improved recovery of markers from the brain into the blood in every tested animal. Overall, our work establishes a noninvasive, spatially-specific means of monitoring gene delivery outcomes and endogenous signaling in mammalian brains, opening up possibilities for brain research and noninvasive monitoring of gene therapies in the brain.
RESUMO
STUDY OBJECTIVES: Asian Americans report higher rates of insufficient sleep than non-Hispanic Whites (NHWs). It is unclear how sleep outcomes differ among disaggregated Asian subgroups. METHODS: The National Health Interview Survey (2006-2018) was used to analyze self-reported sleep duration and quality measures for Asian American subgroups (Chinese [n = 11,056], Asian Indian [n = 11,249], Filipino [n = 13,211], and other Asians [n = 21,767]). Outcomes included hours of sleep per day, the number of days reporting trouble falling asleep, staying asleep, waking up rested, and taking sleep medication in the past week. Subsetted multivariate logistic regression was used to assess factors impacting sleep outcomes by ethnicity. RESULTS: 29.2% of NHWs, 26.4% of Chinese, 24.5% of Asian Indians, and 38.4% of Filipinos reported insufficient sleep duration. Filipinos were less likely to report sufficient sleep duration (odds ratio 0.55, [confidence interval 95% 0.50-0.59]) and more likely to report trouble falling asleep (1.16 [1.01-1.33]) than NHWs. Chinese and Asian Indians had less trouble staying asleep (0.67 [0.58-0.77], 0.51 [0.44-0.59]) and falling asleep (0.77 [0.66-0.89], 0.72, [0.62-0.82]) than NHWs, and Asian Indians were more likely to wake feeling well rested (1.66 [1.48-1.87]). All Asian subgroups were less likely to report using sleep medications than NHWs. Foreign-born status had a negative association with sufficient sleep duration in Filipinos but a positive association in Asian Indians and Chinese. CONCLUSIONS: Filipinos report the highest burden of poor sleep outcomes, and Asian Indians report significantly better sleep outcomes. These findings highlight the importance of disaggregating Asian ethnic subgroups to address their health needs. CITATION: Wang RZ, Jamal A, Wang Z, et al. Toward precision sleep medicine: variations in sleep outcomes among disaggregated Asian Americans in the National Health Interview Survey (2006-2018). J Clin Sleep Med. 2023;19(7):1259-1270.