The power of rotation schedules on the career selection decisions of medical students.

Choosing a career pathway in medicine is a high stakes decision for both medical students and the field of medicine as a whole. While past research has examined how characteristics of the medical student or specialties influence this decision, we introduce temporal elements as novel variables influencing career selection decisions in medicine. Specifically, we investigate how timing and duration of residency options, based on a rotation schedule that medical students have limited control over, influence their career selection decisions. An archival study investigating 5 years of medical student rotation schedules (N = 115) reveals that clinical rotation options appearing earlier and more often in the schedule were more likely to be selected. Moreover, timing and duration of exposure interacted such that residency options appearing later in the schedules were more likely to be selected if they also appeared more often. Conditional logistic regressions using student fixed-effects to control for idiosyncratic medical student differences (i.e., gender, & debt, etc.), and residency fixed-effects to control for idiosyncratic residency differences (income, and lifestyle, etc.), revealed the rotation schedule had a significant impact on residency selection decisions even when controlling for factors typically influencing this decision. Medical students' career decisions are influenced by when and how long different choice options appear in their rotation schedule, especially when they have limited influence over this schedule. The results have implications for healthcare policy by highlighting a tool for adjusting physician workforce composition by broadening exposure to a greater array of career options.

Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations.

Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to the evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signaling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g., strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation.

Tyrosine kinase inhibition reverses TDP-43 effects on synaptic protein expression, astrocytic function and amino acid dis-homeostasis.

The trans-activating response of DNA/RNA-binding protein (TDP)-43 pathology is associated with many neurodegenerative diseases via unknown mechanisms. Here, we use a transgenic mouse model over-expressing human wild-type neuronal TDP-43 to study the effects of TDP-43 pathology on glutamate metabolism and synaptic function. We found that neuronal TDP-43 over-expression affects synaptic protein expression, including Synapsin I, and alters surrounding astrocytic function. TDP-43 over-expression is associated with an increase in glutamate and γ-amino butyric acid and reduction of glutamine and aspartate levels, indicating impairment of presynaptic terminal. TDP-43 also decreases tricarboxylic acid cycle metabolism and induces oxidative stress via lactate accumulation. Neuronal TDP-43 does not alter microglia activity or significantly changes systemic and brain inflammatory markers compared to control. We previously demonstrated that brain-penetrant tyrosine kinase inhibitors (TKIs), nilotinib and bosutinib, reduce TDP-43-induced cell death in transgenic mice. Here, we show that TKIs reverse the effects of TDP-43 on synaptic proteins, increase astrocytic function and restore glutamate and neurotransmitter balance in TDP-43 mice. Nilotinib, but not bosutinib, reverses mitochondrial impairment and oxidative metabolism. Taken together, these data suggest that TKIs can attenuate TDP-43 toxicity and improve synaptic and astrocytic function, independent of microglial or other inflammatory effects. In conclusion, our data demonstrate novel mechanisms of the effects of neuronal TDP-43 over-expression on synaptic protein expression and alteration of astrocytic function.