Stroke Ready Intervention: Community Engagement to Decrease Prehospital Delay.

BACKGROUND: Time-limited acute stroke treatments are underused, primarily due to prehospital delay. One approach to decreasing prehospital delay is to increase stroke preparedness, the ability to recognize stroke, and the intention to immediately call emergency medical services, through community engagement with high-risk communities. METHODS AND RESULTS: Our community-academic partnership developed and tested "Stroke Ready," a peer-led, workshop-based, health behavior intervention to increase stroke preparedness among African American youth and adults in Flint, Michigan. Outcomes were measured with a series of 9 stroke and nonstroke 1-minute video vignettes; after each video, participants selected their intended response (primary outcome) and symptom recognition (secondary outcome), receiving 1 point for each appropriate stroke response and recognition. We assessed differences between baseline and posttest appropriate stroke response, which was defined as intent to call 911 for stroke vignettes and not calling 911 for nonstroke, nonemergent vignettes and recognition of stroke. Outcomes assessments were performed before workshop 1 (baseline), at the conclusion of workshop 2 (immediate post-test), and 1 month later (delayed post-test). A total of 101 participants completed the baseline assessment (73 adults and 28 youths), 64 completed the immediate post-test, and 68 the delayed post-test. All participants were African American. The median age of adults was 56 (interquartile range 35-65) and of youth was 14 (interquartile range 11-16), 65% of adults were women, and 50% of youths were women. Compared to baseline, appropriate stroke response was improved in the immediate post-test (4.4 versus 5.2, P<0.01) and was sustained in the delayed post-test (4.4 versus 5.2, P<0.01). Stroke recognition did not change in the immediate post-test (5.9 versus 6.0, P=0.34), but increased in the delayed post-test (5.9 versus 6.2, P=0.04). CONCLUSIONS: Stroke Ready increased stroke preparedness, a necessary step toward increasing acute stroke treatment rates. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01499173.

C/EBP homologous protein-induced macrophage apoptosis protects mice from steatohepatitis.

Nonalcoholic fatty liver disease is a heterogeneous disorder characterized by liver steatosis; inflammation and fibrosis are features of the progressive form nonalcoholic steatohepatitis. The endoplasmic reticulum stress response is postulated to play a role in the pathogenesis of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. In particular, C/EBP homologous protein (CHOP) is undetectable under normal conditions but is induced by cellular stress, including endoplasmic reticulum stress. Chop wild type (Chop(+/+)) and knock-out (Chop(-/-)) mice were used in these studies to elucidate the role of CHOP in the pathogenesis of fatty liver disease. Paradoxically, Chop(-/-) mice developed greater liver injury, inflammation, and fibrosis than Chop(+/+) mice, with greater macrophage activation. Primary, bone marrow-derived, and peritoneal macrophages from Chop(+/+) and Chop(-/-) were challenged with palmitic acid, an abundant saturated free fatty acid in plasma and liver lipids. Where palmitic acid treatment activated Chop(+/+) and Chop(-/-) macrophages, Chop(-/-) macrophages were resistant to its lipotoxicity. Chop(-/-) mice were sensitized to liver injury in a second model of dietary steatohepatitis using the methionine-choline-deficient diet. Analysis of bone marrow chimeras between Chop(-/-) and Chop(+/+) mice demonstrated that Chop in macrophages protects from liver injury and inflammation when fed the methionine-choline-deficient diet. We conclude that Chop deletion has a proinflammatory effect in fatty liver injury apparently due to decreased cell death of activated macrophages, resulting in their net accumulation in the liver. Thus, macrophage CHOP plays a key role in protecting the liver from steatohepatitis likely by limiting macrophage survival during lipotoxicity.