There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [11C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [11C]DPA-713 binding to TSPO, may be linked to history of NFL play. [11C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play.
Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [11C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [11C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test–retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings.
Problem Medical schools face the challenge of developing efficacious resources to promote well-being and foster resilience in students. The authors developed, implemented, and evaluated a shame resilience seminar for second-year clerkship medical students. Approach In February 2018, the authors conducted a 2.5-hour seminar (part of a longitudinal series) about shame, a common and potentially damaging emotion. The seminar consisted of a large-group session to introduce the psychology of shame, during which speakers shared their personal experiences with the emotion. Next, a small-group session allowed students to discuss their reactions to the large-group content in a safe and familiar environment. Before the seminar, faculty development was provided to small-group leaders (upper-level medical students and faculty) to increase their comfort leading discussions about shame. Students completed a pre/post retrospective survey immediately following the seminar. Outcomes The authors found statistically significant increases in students’ confidence in identifying shame and differentiating it from guilt; in their attitudes regarding the importance of identifying shame reactions in themselves and others; and in their willingness to reach out to others during a shame reaction. Surveys of group leaders revealed no reports of significant student distress during or after the seminar. Next Steps This seminar represents a reproducible means of promoting shame resilience in medical students. The speakers’ personal shame experiences and the safety of the small groups for discussions about shame were central to the seminar’s apparent success. Next steps include developing an empirically derived, longitudinal shame resilience curriculum spanning the medical school years.
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