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OBJECTIVE: To relate volumetric magnetic resonance imaging (MRI) findings to hypothermia therapy and neurosensory impairments. STUDY DESIGN: Newborns > or =36 weeks' gestation with hypoxic-ischemic encephalopathy who participated in the National Institute of Child Health and Human Development hypothermia randomized trial at our center were eligible. We determined the relationship between hypothermia treatment and usual care (control) to absolute and relative cerebral tissue volumes. Furthermore, we correlated brain volumes with death or neurosensory impairments at 18 to 22 months. RESULT: Both treatment groups were comparable before randomization. Total brain tissue volumes did not differ in relation to treatment assignment. However, relative volumes of subcortical white matter were significantly larger in hypothermia-treated than control infants. Furthermore, relative total brain volumes correlated significantly with death or neurosensory impairments. Relative volumes of the cortical gray and subcortical white matter also correlated significantly with Bayley Scales psychomotor development index. CONCLUSION: Selected volumetric MRI findings correlated with hypothermia therapy and neurosensory impairments. Larger studies using MRI brain volumes as a secondary outcome measure are needed. [ABSTRACT FROM AUTHOR]

Objectives: Preterm infants often experience multiple painful procedures during their stay in neonatal intensive care units (NICUs). The objectives of this study were to evaluate behavioral responses to heelstick in preterm newborns, characterize developmental changes and the effects of other demographic and clinical variables on the pain response, and estimate the contributions of individual Neonatal Infant Pain Scale (NIPS) behaviors to the summary pain score., Methods: A longitudinal study was conducted to evaluate the behavioral responses of 35 preterm newborns to multiple heelstick procedures during their stay in the NICU. Sixty-one video recordings of blood collection by heel lance were evaluated for behavioral pain response using the NIPS. Generalized linear mixed models were calculated to address the study objectives., Results: The increases in NIPS scores from the baseline to the blood draw were highly significant (mean baseline score=3.34, mean blood draw score=5.45, p<0.001). The newborns' pain responses increased an average of 0.23 points on the NIPS scale each week (p=0.002). Lower NIPS scores during the heelstick procedure were associated with four clinical variables: younger post-menstrual age at birth, lower birthweight, mechanical ventilation, and longer length of stay in the NICU. Crying, arousal state, and facial grimace contributed more than 85% of the increase in NIPS scores during the heelstick procedure., Discussion: While behavioral responses to pain are attenuated in young, severely ill preterm newborns, they can be reliably detected. The most robust pain behaviors are crying, changes in arousal state, and facial grimacing.

Autophagy, a highly conserved cellular mechanism wherein various cellular components are broken down and recycled through lysosomes, has been implicated in the development of heart failure. However, tools to measure autophagic flux in vivo have been limited. Here, we tested whether monodansylcadaverine (MDC) and the lysosomotropic drug chloroquine could be used to measure autophagic flux in both in vitro and in vivo model systems. Using HL-1 cardiac-derived myocytes transfected with GFP-tagged LC3 to track changes in autophagosome formation, autophagy was stimulated by mTOR inhibitor rapamycin. Administration of chloroquine to inhibit lysosomal activity enhanced the rapamycin-induced increase in the number of cells with numerous GFP-LC3-positive autophagosomes. The chloroquine-induced increase of autophagosomes occurred in a dose-dependent manner between 1 microM and 8 microM, and reached a maximum 2 hour after treatment. Chloroquine also enhanced the accumulation of autophagosomes in cells stimulated with hydrogen peroxide, while it attenuated that induced by Bafilomycin A1, an inhibitor of V-ATPase that interferes with fusion of autophagosomes with lysosomes. The accumulation of autophagosomes was inhibited by 3-methyladenine, which is known to inhibit the early phase of the autophagic process. Using transgenic mice expressing 3 mCherry-LC3 exposed to rapamycin for 4 hr, we observed an increase in mCherry-LC3-labeled autophagosomes in myocardium, which was further increased by concurrent administration of chloroquine, thus allowing determination of flux as a more precise measure of autophagic activity in vivo. MDC injected 1 hr before sacrifice colocalized with mCherry-LC3 puncta, validating its use as a marker of autophagosomes. This study describes a method to measure autophagic flux in vivo even in non-transgenic animals, using MDC and chloroquine.