Magnetic Resonance Prediction of Lung Maturity in Fetuses With Congenital Diaphragmatic Hernia.

ABSTRACT: To determine if lung to liver MR T2 signal ratio is predictive of neonatal outcome in fetuses with congenital diaphragmatic hernia (CDH).After Interal Review Board approval, the PACS systems at the University of Washington and University of Utah were searched for cases having an in utero fetal MR examination diagnostic of CDH. Inclusion criteria were at least 1 prior ultrasound demonstrating a CDH and an MR obtained within 1 week of that prior ultrasound.A total of 69 patients from the University of Utah and 13 from the University of Washington satisfied the inclusion criteria for a total of 82. After adjusting for gestational age and contralateral lung volume, there was little apparent association between contralateral lung to liver MR T2 signal and 5-minute Apgar score and neonatal mortality When considering neonatal Apgar and mortality, increasing contralateral lung volume was significantly associated with lower risk (hazard ratio, 0.40 per doubling; 95% confidence interval, 0.24-0.69; P = 0.001) as expected.Our data demonstrate that the lung to liver MR signal ratio was not predictive of outcome. The measurement of contralateral lung area, and gestational age at the time of the examination (time of diagnosis) are still the best predictors of poor neonatal outcome.

Altered zinc balance in the Atp7b-/- mouse reveals a mechanism of copper toxicity in Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the ATP7B gene that affects copper transport in the body. ATP7B mutation damages copper transporter function, ultimately resulting in excessive copper accumulation and subsequent toxicity in both the liver and brain. Mechanisms of copper toxicity, however, are not well defined. The Atp7b-/- mouse model is well-characterized and presents a hepatic phenotype consistent with WD. In this study, we found that the untreated Atp7b-/- mice accumulate approximately 2-fold excess hepatic zinc compared to the wild type. We used targeted transcriptomics and proteomics to analyze the molecular events associated with zinc and copper accumulation in the Atp7b-/- mouse liver. Altered gene expression of Zip5 and ZnT1 zinc transporters indicated a transcriptional homeostatic response, while increased copper/zinc ratios associated with high levels of metallothioneins 1 and 2, indicated altered Zn availability in cells. These data suggest that copper toxicity in Wilson disease includes effects on zinc-dependent proteins. Transcriptional network analysis of RNA-seq data reveals an interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. In the context of previous research, these observations support the hypothesis that mechanisms of copper toxicity include disruption of intracellular zinc distribution in liver cells. The translational significance of this work lies in oral zinc supplementation in treatment for WD, which is thought to mediate protective effects through the induction of metallothionein synthesis in the intestine. This work indicates broader impacts of altered zinc-copper balance in WD, including global transcriptional responses and altered zinc balance in the liver.

24-h sleep deprivation impairs early attentional modulation of neural processing: An event-related brain potential study.

Prior research indicates sleep deprivation negatively impacts selective attention, although less is known about the neural bases of these effects. The present study used event-related brain potentials (ERPs) to examine whether the effects of total sleep deprivation could be traced to the earliest stages of sensory processing influenced by selective attention. Participants were randomly assigned either to a regular sleep or 24-h total sleep deprivation condition. Following either sleep deprivation or regular sleep, participants completed a dichotic listening selective attention task while ERPs were acquired. Well-rested participants showed typical attentional modulation of the N1 between 150 and 250 msec, with larger amplitude responses to attended relative to unattended auditory probes. In contrast, these effects were significantly reduced in sleep-deprived participants, who did not show significant effects of selective attention on early neural processing. Similar group differences were observed in the later processing negativity, from 300 to 450 msec. Taken together, these results indicate that 24-h total sleep deprivation can significantly reduce, or eliminate, early effects of selective attention on neural processing.