Midbrain neurons of the centrally projecting Edinger–Westphal nucleus (EWcp) are activated by alcohol, and enriched with stress-responsive neuropeptide modulators (including the paralog of corticotropin-releasing factor, urocortin-1). Evidence suggests that EWcp neurons promote behavioral processes for alcohol-seeking and consumption, but a definitive role for these cells remains elusive. Here we combined targeted viral manipulations and gene array profiling of EWcp neurons with mass behavioral phenotyping in C57BL/6 J mice to directly define the links between EWcp-specific urocortin-1 expression and voluntary binge alcohol intake, demonstrating a specific importance for EWcp urocortin-1 activity in escalation of alcohol intake.

Accurate assessment of proteinuria in pediatric patients infected with the human immunodeficiency virus (HIV) is limited by constraints imposed by timed urine collections and low creatinine excretion in very ill patients with low muscle mass. We therefore sought to validate the use of random urine specimens to quantitate total protein and creatinine excretion in a population of 236 HIV-positive children. A mathematical derivation for estimating urine volume (V) was constructed. The accuracy of the final calculation [V = 832 (kL/Ucr)BSA] (where k = constant, L body length, UCr urine creatinine and BSA body surface area) was tested by regression analysis comparing the calculated and measured volume of 31 urines from ambulatory HIV-negative patients. The correlation coefficient was highly significant (r = 0.77, P < or = 0.0001). The relationship was also applied to 23 timed urine specimens from HIV-positive patients with similar significance (r = 0.87, P < 0.0001). A regression analysis of measured proteinuria against the urine protein: creatinine ratio (Upr/Ucr) in these same urines from the HIV-positive patients yielded a significant relationship both in the linear (r = 0.95, y = 0.4x) and the logarithmic regression (r = 0.97, y = x + 0.4). These data support the use of random Upr/Ucr ratios to estimate daily proteinuria in HIV-infected pediatric patients despite low creatinine excretion rates. The previously accepted values continue to apply, with Upr/Ucr < or = 2.0 considered normal and > 2.0 representative of nephrotic proteinuria.

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