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Monoaminergic modulation of decision-making under risk of punishment in a rat model

Blaes, Shelby L; Orsini, Caitlin A; Mitchell, Marci R; Spurrell, Megan S; Betzhold, Sara M; Vera, Kenneth; Bizon, Jennifer L; Setlow, Barry
The ability to decide advantageously among options that vary in both their risks and rewards is critical for survival and well-being. Previous work shows that some forms of risky decision-making are robustly modulated by monoamine signaling, but it is less clear how monoamine signaling modulates decision-making under risk of explicit punishment. The goal of these experiments was to determine how this form of decision-making is modulated by dopamine, serotonin, and norepinephrine signaling, using a task in which rats choose between a small, 'safe' food reward and a large food reward associated with variable risks of punishment. Preference for the large, risky reward (risk-taking) was reduced by administration of a D2/3 dopamine receptor agonist (bromocriptine) and a selective D2 agonist (sumanirole). The selective D3 agonist PD128907 appeared to attenuate reward discrimination abilities but did not affect risk-taking per se. In contrast, drugs targeting serotonergic and noradrenergic signaling had few if any effects on choice behavior. These data suggest that in contrast to other forms of risky decision-making, decision-making under risk of punishment is selectively modulated by dopamine signaling, predominantly through D2 receptors.
PMID: 30394882
ISSN: 1473-5849
CID: 4851752

Validation of a new American Association for the Surgery of Trauma (AAST) anatomic severity grading system for acute cholecystitis

Vera, Kenneth; Pei, Kevin Y; Schuster, Kevin M; Davis, Kimberly A
BACKGROUND:The American Association for the Surgery of Trauma (AAST) established anatomic grading to facilitate risk stratification and risk-adjusted outcomes in emergency general surgery. Cholecystitis severity was graded based on clinical, imaging, operative, and pathologic criteria. We aimed to validate the AAST anatomic grading system for acute cholecystitis. METHODS:This is a retrospective cohort study including consecutive patients admitted with acute cholecystitis at an urban, tertiary medical center between 2013 and 2016. Grade 1 is acute cholecystitis, Grade 2 is gangrenous or emphysematous cholecystitis, Grade 3 is localized perforation, and Grades 4 and 5 have regional and systemic peritonitis, respectively. Concordance between the AAST grade and outcome including mortality, length of stay (LOS), ICU use, readmission, and complications were assessed using logistic regression. RESULTS:A total of 315 patients were included. There was very good inter-rater (two independent raters) reliability for anatomic grading, κ = 1.00, p < 0.005. The majority of patients were Grade 1 or Grade 2 (94%). Incidence of complications, LOS, ICU use, and any adverse event increased with increasing anatomic grade. When compared to Grade 1 disease, patients with Grade 2 were more likely to undergo cholecystectomy (OR 4.07 [1.93-8.56]). Grade 3 patients were at higher risk of adverse events (OR 3.83 [1.34-10.94]), longer LOS (OR 1.73 [1.03-2.92]), and ICU use (OR 8.07 [2.43-26.80]). CONCLUSIONS:AAST severity scores were independently associated with clinical outcomes in patients with acute cholecystitis. Despite low-grade disease, complications were common, and therefore a refinement of the scoring system may be necessary for more granular prediction. LEVEL OF EVIDENCE:Epidemiologic/prognostic, level III.
PMID: 29271871
ISSN: 2163-0763
CID: 4851742