Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine-and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal dopaminergic neurotransmission while altering ethanol consumption. Examining TBI effects on ethanol responsitivity will improve our understanding of alcohol use post-TBI in humans.

BackgroundPhysician burnout and emotional distress are associated with work dissatisfaction and provision of suboptimal patient care. Little is known about burnout among nephrology fellows.MethodsValidated items on burnout, depressive symptoms, and well being were included in the American Society of Nephrology annual survey emailed to US nephrology fellows in May to June 2018. Burnout was defined as an affirmative response to two single-item questions of experiencing emotional exhaustion or depersonalization.ResultsResponses from 347 of 808 eligible first- and second-year adult nephrology fellows were examined (response rate=42.9%). Most fellows were aged 30–34 years (56.8%), male (62.0%), married or partnered (72.6%), international medical graduates (62.5%), and pursuing a clinical nephrology fellowship (87.0%). Emotional exhaustion and depersonalization were reported by 28.0% and 14.4% of the fellows, respectively, with an overall burnout prevalence of 30.0%. Most fellows indicated having strong program leadership (75.2%), positive work-life balance (69.2%), presence of social support (89.3%), and career satisfaction (73.2%); 44.7% reported a disruptive work environment and 35.4% reported depressive symptoms. Multivariable logistic regression revealed a statistically significant association between female gender (odds ratio [OR], 1.90; 95% confidence interval [95% CI], 1.09 to 3.32), poor work-life balance (OR, 3.97; 95% CI, 2.22 to 7.07), or a disruptive work environment (OR, 2.63; 95% CI, 1.48 to 4.66) and burnout.ConclusionsAbout one third of US nephrology fellows surveyed reported experiencing burnout and depressive symptoms. Further exploration of burnout—especially that reported by female physicians, as well as burnout associated with poor work-life balance or a disruptive work environment—is warranted to develop targeted efforts that may enhance the educational experience and emotional well being of nephrology fellows.

Background Fetal exposure to alcohol can have multiple deleterious effects, including learning disorders and behavioral and executive functioning abnormalities, collectively termed fetal alcohol spectrum disorders. Neonatal mice lacking both calcium/calmodulin-stimulated adenylyl cyclases (ACs) 1 and 8 demonstrate increased vulnerability to ethanol-induced neurotoxicity in the striatum compared to wild type (WT) controls. However, the developmental impact on surviving neurons is still unclear. Methods WT and AC1/8 knock-out (DKO) mice were administered one dose of ethanol (2.5g/kg) between postnatal days 5-7 (P5-7). At P30, brains were removed and processed for Golgi-Cox staining. Medium spiny neurons (MSNs) from the caudate putamen were analyzed for changes in dendritic complexity; number of branches, branch points and terminals, total and average dendritic length; spine density, and soma size. Results Ethanol significantly reduced the dendritic complexity and soma size in surviving MSNs regardless of genotype without affecting spine density. In the absence of ethanol, genetic deletion of AC1/8 reduced the dendritic complexity, number of branch points, spine density and soma size of MSNs compared to WT controls. Conclusion These data indicate that neonatal exposure to a single dose of ethanol is sufficient to cause long-term alterations in the dendritic complexity of MSNs and that this outcome is not altered by the functional status of AC1 and AC8. Therefore, although deletion of AC1/8 demonstrates a role for the adenylyl cyclases in normal morphologic development and ethanol-induced neurodegeneration, loss of AC1/8 activity does not exacerbate the effects of ethanol on dendritic morphology or spine density.

The purpose of this study was to examine the benefits, challenges, program characteristics and instructional approaches of an El Sistema inspired (ESI) after-school string program developed as a university–school partnership. Case study methodology was used to examine the program. Fifth-grade students received 75 minutes of after-school instruction four days per week. Two graduate students in music performance and the elementary school orchestra/general music teacher were the program’s lead teachers. Eight additional university students gave pull-out lessons. The program featured many “distinguishing characteristics” described in the ESI literature. The learning environment included large ensemble, sectional learning, and individual lessons. The repertoire learned was standard for American beginning string classes. Teachers provided rigorous expectations for the students to strive for excellence, a safe and supportive learning environment, flexible teaching, and peer-mentoring opportunities. Benefits included high levels of musical achievement, increased learning opportunities, perceived benefits of discipline, perseverance, positive attitude, and hard work. Instructional challenges included low attendance, curricular balance, and teacher collaboration. The intensity and frequency of instruction were found to be the source of most benefits and challenges reported by the participants.