Lifetime non-fatal overdose experiences among at-risk adolescents and young adults in the emergency department with past-year opioid use in the USA.

BACKGROUND: Adolescents and young adults with risk factors for opioid misuse and opioid use disorder are at elevated risk for overdose. We examined prior non-fatal overdose experiences among at-risk adolescents/young adults to inform prevention efforts. METHODS: Adolescents/young adults (ages 16-30) in two US emergency departments self-reporting past year opioid misuse or opioid use plus a misuse risk factor completed a baseline survey as part of an ongoing randomised controlled trial. We describe baseline factors associated with (a) overall non-fatal overdose experiences and (b) groups based on substance(s) used during the worst overdose experience. RESULTS: Among 771 participants (27.9% male), 40.7% reported a non-fatal overdose experience. Compared with those without a prior overdose experience, those with prior overdose experience(s) were less likely to be heterosexual, and more likely to report a prior suicide attempt and greater peer substance misuse. Regarding the worst overdose experience, substance(s) included: 36.6% alcohol only, 28.0% alcohol and cannabis, 22.6% alcohol with other substance(s) and 12.7% other substance(s) only (eg, opioids). Compared with the alcohol only group, the alcohol and cannabis group were younger and less likely to be heterosexual; the alcohol with other substance(s) group were older and had greater peer substance misuse; and the other substance(s) only group were more likely to be male, receive public assistance, screen positive for anxiety and less likely to be heterosexual. CONCLUSIONS: Among at-risk adolescents/young adults, findings support the need for tailored overdose prevention efforts based on substance(s) used, with consideration of sexuality, mental health and peer substance use. TRIAL REGISTRATION NUMBER: NCT04550715.

Recruitment & Retainment of Vascular Surgeons: Prophylactic Measures to Improve the Current Workforce Crisis.

BACKGROUND: The vascular surgery workforce is in jeopardy with the current and increasing shortages. This study explores target populations for recruitment and aims to identify potential modifiable and nonmodifiable risk factors associated with reduced job satisfaction among practicing vascular surgeons to improve retention and prevent early retirement. METHODS: A cross-sectional national survey of surgeons (n = 1,043) was conducted from September 2016 to May 2017. Data included, demographic and occupational characteristics, as well as psychological, work-life balance, work-environment, and job-satisfaction variables. Surgeons were grouped into general surgery (n = 507), obstetrics and gynecology (n = 272), surgical subspecialties (n = 212), and vascular surgery (n = 52). Vascular surgeons were recategorized as more satisfied and less satisfied, and potential risk factors for job dissatisfaction were identified. RESULTS: As compared with general surgeons, obstetrics and gynecology, as well as other surgical subspecialties, vascular surgery tended to be male-dominated with higher rates of non-white, minority groups (P < 0.05). Less vascular surgery respondents were found in the Midwest (P < 0.001). Vascular surgeons worked more hours on average than other surgical fields and were less satisfied with work (P < 0.05). Potential job dissatisfaction risk factors among vascular surgeons include: unhealthy work-life balance, poor camaraderie/coworker dissatisfaction, insufficient hospital support, hostile hospital culture, discontent with supervision, minimal patient diversity, dissatisfaction with work in general, and unhappiness with career choice (P < 0.05). CONCLUSIONS: Recruiting new vascular surgery trainees while simultaneously preventing early retirement and attrition is critical to combatting the current workforce crisis. Potential interventions include (1) re-branding of the field with prioritization of work-life balance, (2) increasing hospital administration's support, (3) creating a collaborative work environment, and (4) facilitating personal accomplishment in work.

Recruitment of General Surgery Residents into Vascular Surgery.

BACKGROUND: Vascular surgery fellowship applications among general surgery residents have declined. Given this steady downward trend in vascular applicants in conjunction with a predicted critical shortage of vascular surgeons, a call to action for increased recruitment is needed. To improve recruitment efforts, a subgroup analysis of general surgery residents was performed to explore factors that influence interest in vascular surgery. METHODS: A cross-sectional national survey of residents (n = 467) was conducted from September 2016 to May 2017. In addition to collection of demographic and occupational characteristics, assessment of psychological, work-life balance, and job-satisfaction variables were obtained. Residents were grouped based on their interest in pursuing a fellowship. Chi-squared and Fisher's exact test was performed to determine significant variables. RESULTS: Residents were grouped into "interest in non-vascular fellowship" (n = 350), "interest in vascular fellowship" (n = 21), and "not interested in fellowship" (n = 96). Significant variables between the groups included age, geographic location, residency size, and type of institution (p < 0.05). Those interested in vascular surgery tended to be older. Residents not interested in fellowship were more commonly located in the Midwest and at smaller, community residencies. No significant difference was found between mental wellness and work-life balance variables. Those residents interested in a vascular surgery fellowship were more dissatisfied with their current salary as compared to other residents (p = 0.021). CONCLUSIONS: There is a predicted critical shortage in the vascular surgery workforce making recruitment of the best and brightest residents into the specialty vital to its future. In order to invigorate and broaden our group of vascular surgeons, focused recruitment of younger, Midwest, general surgery residents at smaller, community programs may provide the most yield. Publicizing the strengths of a vascular surgery career including the diversity of patients, continuity of care, proficiency in technical skill, and higher monetary rewards should be emphasized in recruiting these target populations.

Ubiquitination of alpha-synuclein by Siah-1 promotes alpha-synuclein aggregation and apoptotic cell death.

Point mutations and gene multiplication of alpha-synuclein cause autosomal dominant familial Parkinson's disease (PD). Moreover, alpha-synuclein- and ubiquitin-positive inclusion bodies are the pathological hallmarks of PD and several other neurodegenerative diseases, such as dementia with Lewy bodies and multiple system atrophy. Despite the presence of ubiquitinated alpha-synuclein species in Lewy bodies, the regulation of alpha-synuclein ubiquitination and its role in Lewy body formation and neurodegeneration remain poorly understood. Here, we report that alpha-synuclein interacts and colocalizes with mammalian seven in absentia homologue-1 (Siah-1), a RING-type E3 ubiquitin-protein ligase. Siah-1 binds the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 and facilitates mono- and di-ubiquitination of alpha-synuclein in vivo. The ubiquitination of alpha-synuclein by Siah-1 is disrupted by the PD-linked A30P mutation but not by A53T mutation. We find that Siah-1-mediated ubiquitination does not target alpha-synuclein for degradation by the proteasome, but rather, it promotes alpha-synuclein aggregation and enhances alpha-synuclein toxicity. Our findings suggest that Siah-1-mediated alpha-synuclein ubiquitination may play a critical role in Lewy body formation and PD pathogenesis.

Regulation of synaptophysin degradation by mammalian homologues of seven in absentia.

Synaptophysin is an integral membrane protein of synaptic vesicles characterized by four transmembrane domains with both termini facing the cytoplasm. Although synaptophysin has been implicated in neurotransmitter release, and decreased synaptophysin levels have been associated with several neurodegenerative diseases, the molecular mechanism that regulates the degradation of synaptophysin remains unsolved. Using the cytoplasmic C terminus of synaptophysin as bait in a yeast two-hybrid screen, we identified two synaptophysin-binding proteins, Siah-1A and Siah-2, which are rat homologues of Drosophila Seven in Absentia. We demonstrated that Siah-1A and Siah-2 associate with synaptophysin both in vitro and in vivo and defined the binding domains of synaptophysin and Siah that mediate their association. Siah proteins exist in both cytosolic and membrane-associated pools and co-localize with synaptophysin on synaptic vesicles and early endosomes. In addition, Siah proteins interact specifically with the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 and facilitate the ubiquitination of synaptophysin. Furthermore, overexpression of Siah proteins promotes the degradation of synaptophysin via the ubiquitin-proteasome pathway. Our findings indicate that Siah proteins function as E3 ubiquitin-protein ligases to regulate the ubiquitination and degradation of synaptophysin.