Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0.05). In the transport study, exosomes also enhanced the permeability of rhodamine 123 in a co-cultured monolayer of brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.

The key factor in accomplishing this DM program is meeting the health care needs of a unique population-the Hispanic-American community. Clinicians, administrators, and public health officials should note that understanding the broad parameters of a culture is essential to providing quality care to individuals, families, and communities.

Background Despite the empirical literature demonstrating the efficacy of antidepressant medications for treatment of depression disorder, these medications’ effect on patients’ overall well-being and health-related quality of life (HRQoL) remains controversial. This study investigates the effect of antidepressant medication use on patient-reported HRQoL for patients who have depression. Methods A comparative cohort, secondary database analysis was conducted using data from the United States’ Medical Expenditures Panel Survey for patients who had depression. HRQoL was measured using the SF-12 and reported as physical and mental component summaries (PCS and MCS). A cohort of patients that used antidepressant medications were compared to a cohort of patients that did not. Univariate and multivariate difference-in-differences (D-I-D) analyses were used to assess the significance of the mean difference of change on the PCS and MCS from baseline to follow-up. Results On average, 17.5 million adults were diagnosed with depression disorder each year during the period 2005–2016. The majority were female (67.9%), a larger proportion of whom received antidepressant medications (60.5% vs. 51.5% of males). Although use of antidepressants was associated with some improvement on the MCS, D-I-D univariate analysis revealed no significant difference between the two cohorts in PCS (–0.35 vs. –0.34, p = 0.9595) or MCS (1.28 vs. 1.13, p = 0.6405). The multivariate D-I-D analyses ensured the robustness of these results. Conclusion The real-world effect of using antidepressant medications does not continue to improve patients’ HRQoL over time. Future studies should not only focus on the short-term effect of pharmacotherapy, it should rather investigate the long-term impact of pharmacological and non-pharmacological interventions on these patients’ HRQoL.

Background:The primary objective of our study was to investigate the prevalence of off-label antidepressant drug use in insomnia. The secondary objective was to compare prescribing patterns between off-label antidepressants vs hypnotics approved by the US Food and Drug Administration for insomnia, with particular emphasis on socioeconomic characteristics of patients and physicians.Methods:We undertook a secondary data analysis using the national longitudinal database from the 2006 National Ambulatory Medical Care Survey. Subjects were identified from outpatient visits in which at least one insomnia drug was prescribed. A series of weighted Chi-squared statistics was used to compare drug use for insomnia across various patient and physician characteristics. Multivariate logistic regression was conducted to identify factors associated with off-label antidepressant drug use.Results:Among 901.95 million outpatient visits that took place in the US in 2006, an estimated 30.43 million visits included at least one drug prescription for insomnia. Off-label antidepressants were prescribed significantly more frequently (45.1%) than nonbenzodiazepine z-hypnotics (43.2%) and benzodiazepines (11.7%). Insomnia prescribing patterns were significantly influenced by physician specialty and physician office settings. Pediatricians (odds ratio [OR]: 65.892; 95% confidence interval [CI]: 5.536–810.564) and neurologists (OR: 4.784; 95% CI: 2.044–11.201) were more likely to prescribe off-label antidepressants than psychiatrists. Self-paying patients were more likely to receive off-label antidepressants as treatment for insomnia than patients with private insurance (OR 2.594; 95% CI: 1.128–5.967).Conclusion:Our findings indicate significant socioeconomic disparities in the use of off-label antidepressants. Future studies might explore interventional and educational strategies to ensure well informed clinical decisions that can withstand pharmaceutical marketing strategies and diagnostic uncertainties regarding the treatment of insomnia.

No outside funding supported this study. The authors report no potential conflicts of interest relevant to this research. Lai and Ting contributed to study concept and design and collected the data, along with the other authors. Data interpretation was performed by Lai, Koh, Obi, Ho, and Ting. The manuscript was written and revised by Lai, Koh, and Ho, with assistance from Ting and Obi.