Academic Productivity of Applicant and Program as Predictors of a Future Academic Career in Neurosurgery.

BACKGROUND AND OBJECTIVES: Academic productivity is viewed as a critical objective factor for a neurosurgery residency applicant. There has been a consistent rise in academic productivity over the last decade, but a lack of consistent data on the utility of this in helping neurosurgery residency programs identify which applicants will enter academic neurosurgery. This cross-sectional study evaluates the predictiveness of academic productivity before and during residency on career choice, both independent and dependent of training environment. METHODS: The 116 accredited neurosurgery residency programs were split into 4 quartile groups based on their 2022 Doximity rankings. Six neurosurgery residency programs were randomly selected from each quartile. Publicly available information including number and type (before or during residency) of publication and type of employment (academic vs nonacademic) was collected on neurosurgeons who matriculated into residency in the year 2000 or later. Multivariable logistic regression was used to explore the associations among neurosurgeon and program characteristics, and an academic career. RESULTS: A total of 557 neurosurgeons were identified. Group 1 (n = 194) had the highest median publications during residency total (12) and first author (5), as well as the highest percentage of neurosurgeons who attended a top 20 medical school (38.7%), hold a higher educational degree (20.6%), and pursued an academic career (72.2%). Neither attending a top 20 medical school, holding a higher educational degree, nor publications were significant multivariable predictors of an academic career. Being in group 1 was the only significant predictor of entering an academic career across analyses. CONCLUSION: Only residency group ranking, not academic productivity, predicted a future academic career. For residency programs evaluating applicants as future academic neurosurgeons, this suggests that program environment is more predictive than traditionally valued characteristics such as research productivity. Additional work is needed to elucidate characteristics or practices by which future academic neurosurgeons can be identified.

Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy.

This article describes the critical role of neurosteroids in postpartum depression (PPD) and outlines the landmark pharmacological journey of brexanolone as a first-in-class neurosteroid antidepressant with significant advantages over traditional antidepressants. PPD is a neuroendocrine disorder that affects about 20% of mothers after childbirth and is characterized by symptoms including persistent sadness, fatigue, dysphoria, as well as disturbances in cognition, emotion, appetite, and sleep. The main pathology behind PPD is the postpartum reduction of neurosteroids, referred to as neurosteroid withdrawal, a concept pioneered by our preclinical studies. We developed neurosteroid replacement therapy (NRT) as a rational approach for treating PPD and other conditions related to neurosteroid deficiency, unveiling the power of neurosteroids as novel anxiolytic-antidepressants. The neurosteroid, brexanolone (BX), is a progesterone-derived allopregnanolone that rapidly relieves anxiety and mood deficits by activating GABA-A receptors, making it a transformational treatment for PPD. In 2019, the FDA approved BX, an intravenous formulation of allopregnanolone, as an NRT to treat PPD. In clinical studies, BX significantly improved PPD symptoms within hours of administration, with tolerable side effects including headache, dizziness, and somnolence. We identified the molecular mechanism of BX in a neuronal PPD-like milieu. The mechanism of BX involves activation of both synaptic and extrasynaptic GABA-A receptors, which promote tonic inhibition and serve as a key target for PPD and related conditions. Neurosteroids offer several advantages over traditional antidepressants, including rapid onset, unique mechanism, and lack of tolerance upon repeated use. Some limitations of BX therapy include lack of aqueous solubility, limited accessibility, hospitalization for treatment, lack of oral product, and serious adverse events at high doses. However, the unmet need for synthetic neurosteroids to address this critical condition supersedes these limitations. Recently, we developed novel hydrophilic neurosteroids with a superior profile and improved drug delivery. Overall, approval of BX is a major milestone in the field of neurotherapeutics, paving the way for the development of novel synthetic neurosteroids to treat depression, epilepsy, and status epilepticus.

Efficacy of the FDA-approved cannabidiol on the development and persistence of temporal lobe epilepsy and complex focal onset seizures.

Presently there is no drug therapy for curing epilepsy. Despite many advancements in epilepsy research, nearly 30% of people with epilepsy remain refractory to current antiseizure medications (ASM). Cannabidiol (CBD) has recently been approved as an ASM for pediatric refractory seizures, but it has not been widely tested for adult epileptogenesis and focal onset seizures. In this study, we investigated the efficacy of the FDA-approved CBD in controlling epileptogenesis and complex focal onset seizures using the mouse kindling model of human temporal lobe epilepsy. We also tested combination regimens of CBD with other ASMs. The two primary outcome measures were disease modification and suppression of generalized seizures. In the epileptogenesis study, CBD had a striking effect in attenuating kindling development, with a dose-dependent decrease in behavioral and electrographic seizure activity. In the retention study, mice previously treated with CBD had significantly reduced overall seizure burden, suggesting disease modification. In a fully-kindled seizure study, CBD produced rapid and atypical U-shaped dose-dependent protection against generalized seizures (ED50, 52 mg/kg, i.p.). In a time-course study, CBD showed a maximal protective effect within 1 h of injection, and it declined within 4 h with a biphasic response. In the combination study, CBD produced synergistic/ additive protection when given with midazolam and ganaxolone but not with tiagabine, indicating its strong potential as an adjunct ASM. Finally, the protective effects of CBD were not associated with motor and functional impairments. These preclinical findings demonstrate the potential of adjunct CBD for controlling adult complex focal onset seizure conditions.