Faculty Bibliography

Background/UNASSIGNED:Implementation science (IS) has the potential to serve an important role in encouraging the successful uptake of evidence-based interventions. The current state of IS awareness and engagement among health researchers, however, is relatively unknown. Methods/UNASSIGNED:To determine IS awareness and engagement among health researchers, we performed an online survey of health researchers in the USA in 2018. Basic science researchers were excluded from the sample. Engagement in and awareness of IS were measured with multiple questionnaire items that both directly and indirectly ask about IS methods used. Unrecognized IS engagement was defined as participating in research using IS elements and not indicating IS as a research method used. We performed simple logistic regressions and tested multivariable logistic regression models of researcher characteristics as predictors of IS engagement. Results/UNASSIGNED:< 0.001). Conclusion/UNASSIGNED:Overall, awareness of IS is high among health researchers, yet there is also a high prevalence of unrecognized IS engagement. Efforts are needed to further disseminate what constitutes IS research and increase IS awareness among health researchers.

Nearly 380,000 U.S. service members between 2000 and 2017 were, and at least 300,000 athletes annually are, diagnosed with concussion. It is imperative to establish a gold-standard diagnostic test to quickly and accurately diagnose concussion. In this non-randomized, prospective study, we examined the reliability and validity of a novel neurocognitive assessment tool, the Defense Automated Neurobehavioral Assessment (DANA), designed to be a more sensitive, yet efficient, measure of concussion symptomatology. In this study, the DANA Brief version was compared to an established measure of concussion screening, the Military Acute Concussion Evaluation (MACE), in a group of non-concussed service members. DANA Brief subtests demonstrated low to moderate reliability, as measured by intra-class correlation coefficient (ICC; values range: 0.28-0.58), which is comparable to other computerized neurocognitive tests that are widely-implemented to diagnose concussion. Statistically significant associations were found between learning and memory components of the DANA Brief and the diagnostic MACE cognitive test score (DANA Brief subtests: CDD: R ² = 0.05, p = 0.023; CDS: R ² = 0.10, p = 0.010). However, a more robust relationship was found between DANA Brief components involving attention and working memory, including immediate memory, and the MACE cognitive test score (DANA Brief subtests: GNG: R ² = 0.08, p = 0.003; PRO: R ² = 0.08, p = 0.002). These results provide evidence that the DANA Rapid version, a 5-min assessment self-administered on a hand-held portable device, based on the DANA Brief version, may serve as a clinically useful and improved neurocognitive concussion screen to minimize the time between injury and diagnosis in settings where professional medical evaluation may be unavailable or delayed. The DANA's portability, durability, shorter test time and lack of need for a medical professional to diagnose concussion overcome these critical limitations of the MACE.

Melanoma brain metastasis is the largest cause of melanoma morbidity and mortality, and melanoma has the highest rate of brain metastasis of any cancer. The mechanisms that mediate melanoma brain metastasis remain poorly understood. We characterized patient-derived Short-Term Cultures (STCs) as a novel model system for the study of melanoma brain metastasis. Unbiased proteomics analysis of STCs revealed striking alterations in brain metastasis vs non-brain metastasis derived STCs in proteins related to neurodegeneration. Through in-vivo assays, we show that loss of Amyloid Precursor Protein (APP) in melanoma cells dramatically inhibits melanoma brain metastasis formation without affecting metastasis to other organs and that amyloid beta is the form of APP critically required for melanoma brain metastasis. Additionally, we demonstrate that APP is required for late growth and survival of melanoma cells in the brain parenchyma. Furthermore, we demonstrate that melanoma-derived amyloid beta polarizes astrocytes to an anti-inflammatory secretory phenotype that inhibits microglial phagocytosis of melanoma cells. Finally, we show that treatment of mice with a beta secretase inhibitor (LY2886721), which prevents amyloid beta production, decreases brain metastatic burden. Our results demonstrate a critical role for amyloid beta in melanoma brain metastasis, establish a novel connection between brain metastasis and neurodegenerative pathologies, and show that amyloid beta is a promising therapeutic target for brain metastasis treatment. Studies to further characterize how amyloid beta acts in the melanoma brain metastasis microenvironment are currently underway