Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3-6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3-5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson's trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.
Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30–80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome.
Background Racial and ethnic differences in the use of neuraxial anesthesia compared with general anesthesia are less studied, particularly in obstetrical anesthesia. Here, we aimed to provide an update on the association between race and ethnicity, and the use of neuraxial anesthesia for cesarean delivery in the United States (US). Methods We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File 2019. We extracted cases that had a primary surgery defined with Current Procedural Terminology (CPT) code for cesarean delivery (59510, 59514, and 59515) and cesarean after attempted vaginal delivery in parturients with a prior history of cesarean (59618, 59620, and 59622). Multivariable logistic regression was used to report the association of race and ethnicity with primary anesthetic technique. Results There were 12,876 parturients included in the study. Compared with White parturients, Black (adjusted odds ratio (aOR) = 0.71, 95% confidence interval (CI): 0.57-0.88, p = 0.001) and American Indian or Alaska Native (aOR = 0.22, 95% CI: 0.12-0.40, p < 0.001) parturients had lower odds of receiving neuraxial compared with general anesthesia. There were no significant differences in the odds of neuraxial anesthesia between non-Hispanic and Hispanic cohorts. Conclusions While we do observe racial differences in anesthetic technique, Hispanic patients did not have significantly lower odds of neuraxial anesthesia. This study highlights the importance of an update to prior studies, as the current study suggests a lack of disparity between non-Hispanic and Hispanic parturients. While the results here are encouraging, a multidisciplinary approach is necessary to further address racial disparities.
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