Neonatal inspiratory stridor is an important examination finding that requires immediate and adequate evaluation of the underlying etiology. Depending on the severity of the airway obstruction and the presence or absence of associated symptoms such as respiratory distress and feeding problems, early initiation of a complete diagnostic workup can be crucial. The most common cause of neonatal inspiratory stridor is laryngomalacia, however, several differential diagnoses need to be investigated. More rare causes include oral or laryngeal masses. Teratomas of the head and neck region are one of the most unusual causes of respiratory distress during the neonatal period. We present a case of a mature teratoma in the oropharynx presenting with airway obstruction in a newborn infant. A four-day-old female Caucasian infant was admitted to the neonatal intensive care unit of our hospital because of inspiratory stridor and profound desaturations while feeding. Diagnostic workup by ultrasound, magnetic resonance imaging and flexible endoscopy revealed a pediculated lesion in the pharyngeal region causing intermittent complete airway obstruction. The mass was surgically removed by transoral laser resection on the seventh day of life. Histological evaluation was consistent with a mature teratoma without any signs of malignancy. The further hospital course was uneventful, routine follow-up examinations at 3, 6 and 9 months of age showed no evidence of tumor recurrence. Neonatal stridor is a frequent symptom in the neonatal period and is mostly caused by non-life-threatening pathologies. On rare occasions, however, the underlying conditions are more critical. A careful stepwise diagnostic investigation to rule out these conditions, to identify rare causes and to initiate early treatment is therefore warranted.

FOXO transcription factors control cellular levels of reactive oxygen species (ROS) which critically contribute to cell survival and cell death in neuroblastoma. In the present study we investigated the regulation of C10orf10/DEPP by the transcription factor FOXO3. As a physiological function of C10orf10/DEPP has not been described so far we analyzed its effects on cellular ROS detoxification and death sensitization in human neuroblastoma cells. The effect of DEPP on cellular ROS was measured by catalase activity assay and live cell fluorescence microscopy using the ROS-sensitive dye reduced MitoTracker Red CM-H2XROS. The cellular localization of DEPP was determined by confocal microscopy of EYFP-tagged DEPP, fluorescent peroxisomal- and mitochondrial probes and co-immunoprecipitation of the PEX7 receptor. We report for the first time that DEPP regulates ROS detoxification and localizes to peroxisomes and mitochondria in neuroblastoma cells. FOXO3-mediated apoptosis involves a biphasic ROS accumulation. Knockdown of DEPP prevented the primary and secondary ROS wave during FOXO3 activation and attenuated FOXO3- and H2O2-induced apoptosis. Conditional overexpression of DEPP elevates cellular ROS levels and sensitizes to H2O2 and etoposide-induced cell death. In neuronal cells, cellular ROS are mainly detoxified in peroxisomes by the enzyme CAT/catalase. As DEPP contains a peroxisomal-targeting-signal-type-2 (PTS2) sequence at its N-terminus that allows binding to the PEX7 receptor and import into peroxisomes, we analyzed the effect of DEPP on cellular detoxification by measuring enzyme activity of catalase. Catalase activity was reduced in DEPP-overexpressing cells and significantly increased in DEPP-knockdown cells. DEPP directly interacts with the PEX7 receptor and localizes to the peroxisomal compartment. In parallel, the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARG), a critical regulator of catalase enzyme activity, was strongly upregulated in DEPP-knockdown cells. The combined data indicate that in neuroblastoma DEPP localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification, which sensitizes tumor cells to ROS-induced cell death.

Background: In recent years, cerebral magnetic resonance imaging (MRI) has been increasingly used to depict the wide spectrum of preterm brain injury. Furthermore, it has already been demonstrated by MRI at term-equivalent age (TEA) that preterm infants show delayed brain maturation as compared to term infants, and this delay has been related to neurobehavioral outcome. Objectives: The aim of the current study was to investigate the influence of prevalent neonatal risk factors for adverse outcome on structural brain maturation in very preterm infants at TEA. Methods: One hundred and thirty very preterm infants born at a mean gestational age of 29.7 weeks were included. MRI was performed at TEA and given a validated ‘total maturation score'. Brain maturation scores were compared with neonatal data. Results: In univariate analysis, bronchopulmonary dysplasia (BPD), late-onset sepsis and retinopathy of prematurity were significantly associated with delayed brain maturation. Furthermore, infants with delayed maturation had been ventilated significantly longer and more often suffered from severe arterial hypotension. In multivariate analysis, BPD remained significant as predictor of delayed brain maturation. Conclusions: This study is the first to show that delayed structural brain maturation as evaluated by MRI at TEA is preceded by BPD, which is known to be a predictor of adverse outcome in preterm infants. This finding adds further evidence to show that adverse outcome in preterm infants may have additional neural correlates that exceed common brain injury.