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Background: Fetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L1 cell adhesion molecule (L1) is a target for ethanol (EtOH) developmental neurotoxicity. L1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L1 is also dependent on trafficking through lipid rafts (LRs). Our hypothesis is that L1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L1 phosphorylation/dephosphorylation and LR association in vivo., Methods: Rat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LRs are isolated by sucrose density gradient, and the distribution of L1 in LRs is determined., Results: EtOH at all doses reduced the relative amount of Y1176 dephosphorylation as well as the relative amount of L1 phosphorylated on other tyrosines. The proportion of L1 present in LRs is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls., Conclusions: L1 is a target for EtOH developmental neurotoxicity in vivo., (Copyright © 2012 by the Research Society on Alcoholism.)

Aim: To assess the conclusiveness of the Cochrane Neonatal Reviews (CNRs). We tested the hypotheses that: 1) the majority of the reviews is inconclusive; 2) the majority of reviews recognizes the need for further studies; 3) the ability to reach a conclusion is dependent upon both the number of studies and the number of patients. We also aimed to determine whether the conclusiveness of the CNRs was affected by time., Methods: We selected CNRs available in the Cochrane Library in June 2004. The number of randomized clinical trials (RCTs) found, number of RCTs included for analysis, number of patients enrolled, the stated need for further studies, and the conclusiveness of CNRs were recorded., Results: Out of 170 CNRs, 67.7% were conclusive. The average number of articles was similar, but the total number of patients enrolled was three times higher in the conclusive CNRs. The percentage of articles included in conclusive studies was significantly higher than in inconclusive ones. The vast majority of CNRs recognized the need for further studies. The number of studies included correlated significantly with the total number of patients included. The percentage of conclusive CNRs correlated negatively with year of publication., Conclusion: The majority of CNRs is conclusive, but emphasizes the need for further studies. The ability of a CNR to reach a conclusion is affected by the cumulative sample size and by the number of studies performed. The probability of a newer review to be conclusive is lower than that of an older review.