Jeremy D. Marks

Objective: We assessed the utility of lung ultrasound scores (LUSs) to predict extubation readiness in VLBW infants and determined the effect of postnatal steroids on LUSs in babies who were chronically ventilated for > 30 days. Study design: We measured infants’ LUS scores before planned extubations and determined the success of the subsequent extubation attempts. Results: Overall, LUSs were lower in successfully extubated compared with unsuccessfully extubated infants in the entire population. Similar differences were seen in LUSs between successfully and unsuccessfully extubated chronically ventilated infants. In chronically ventilated infants, LUSs did not differ between infants who did and did not receive dexamethasone. However, dexamethasone-treated infants who extubated successfully had lower scores compared to those who did not. Conclusions: While LUS scores do not predict the need for dexamethasone treatment to promote successful extubation, they do predict subsequent extubation success, irrespective of both dexamethasone treatment and duration of ventilation.

Objective: We assessed the utility of lung ultrasound scores (LUSs) to predict extubation readiness in VLBW infants, and determined the effect of postnatal steroids on LUSs in babies who were chronically ventilated for > 30 days. Study Design: We measured infants’ LUS scores before planned extubations and determined the success of the subsequent extubation attempts. Results: Overall, LUSs were lower in successfully extubated compared with unsuccessfully extubated infants in the entire population. Similar differences were seen in LUSs between successfully and unsuccessfully extubated chronically ventilated infants. In chronically ventilated infants, LUSs did not differ between infants who did and did not receive dexamethasone. However, dexamethasone-treated infants who extubated successfully had lower scores compared to those who did not. Conclusions: While LUS scores do not predict the need for dexamethasone treatment to promote successful extubation, they do predict subsequent extubation success, irrespective of both dexamethasone treatment and duration of ventilation.

Respiratory distress syndrome increases the risk of death and bronchopulmonary dysplasia (BPD) in premature infants. Inhaled nitric oxide (iNO) may reduce these risks. Recent meta-analyses have suggested that iNO is effective only at doses higher than 5 ppm and in infants born to Black mothers. In a randomized, double-blinded, controlled trial, infants born before 32 0/7 weeks gestation, weighing p = 0.017). This increase was due solely to increased BPD in infants weighing 750–999 g (RR 1.33, 95% CI 1.07–1.66, p = 0.009). However, there was no difference in the numbers of infants requiring supplemental oxygen at 40 weeks PMA. Among infants < 750 g, long-iNO-treated infants had a lower cumulative probability of death (χ² 5.12, p = 0.02). Long iNO increased the primary outcome in non-Black infants (RR 1.93, 95% CI 1.20–3.24) but not in Black infants. Understanding how maternal racial identity determines responses of premature infants to iNO may help narrow the gap in health outcomes between Black and non-Black infants.

Preterm infants born before 32 weeks gestation have increased risks for neurodevelopmental impairment at two years of age. How brain function differs between preterm infants with normal or impaired development is unknown. However, abnormal spontaneous motor behavior at 12–15 weeks post-term age is associated with neurodevelopmental impairment. We imaged brain blood oxygen level-dependent signals at term-equivalent age in 62 infants born at <32 weeks gestation and explored whether resting state functional connectivity (rsFC) differed with performances on the General Movement Assessment (GMA) at 12–15 weeks, and Bayley III scores at two years of corrected age. Infants with aberrant general movements exhibited decreased rsFC between the basal ganglia and regions in parietal and frontotemporal lobes. Infants with normal Bayley III cognitive scores exhibited increased rsFC between the basal ganglia and association cortices in parietal and occipital lobes compared with cognitively impaired children. Infants with normal motor scores exhibited increased rsFC between the basal ganglia and visual cortices, compared with children with motor impairment. Thus, the presence of abnormal general movements is associated with region-specific differences in rsFC at term. The association of abnormal long-term neurodevelopmental outcomes with decreased rsFC between basal ganglia and sub-score specific cortical regions may provide biomarkers of neurodevelopmental trajectory and outcome.

Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.

The mechanism for the earliest response of central neurons to hypoxia—an increase in voltage-gated sodium current (I_Na)—has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of Na_V1.2 channels increases I_Na. The time-course for SUMOylation of single Na_V1.2 channels at the cell surface and changes in I_Na coincide, and both are prevented by mutation of Na_V1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of I_Na in hypoxic brain damage, the SUMO pathway and Na_V1.2 are identified as potential targets for neuroprotective interventions.

BACKGROUND AND PURPOSE: Very preterm infants (birth weight, Bayley Scales of Infant and Toddler Development III. RESULTS: Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. CONCLUSIONS: Aberrant general movements at 10–15 weeks9 postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays.

Secreted protein acidic and rich in cysteine (SPARC) induces lipotoxicity in neuroblastoma by regulating transport of albumin complexed with fatty acids