Neurological Consequences of Systemic Inflammation in the Premature Neonate

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain

Maternal Preeclampsia and Neonatal Outcomes

Preeclampsia is a multiorgan, heterogeneous disorder of pregnancy associated with significant maternal and neonatal morbidity and mortality. Optimal strategies in the care of the women with preeclampsia have not been fully elucidated, leaving physicians with incomplete data to guide their clinical decision making. Because preeclampsia is a progressive disorder, in some circumstances, delivery is needed to halt the progression to the benefit of the mother and fetus. However, the need for premature delivery has adverse effects on important neonatal outcomes not limited to the most premature infants. Late-preterm infants account for approximately two thirds of all preterm deliveries and are at significant risk for morbidity and mortality. Reviewed is the current literature in the diagnosis and obstetrical management of preeclampsia, the outcomes of late-preterm infants, and potential strategies to optimize fetal outcomes in pregnancies complicated by preeclampsia

Intrinsic ELMing in ASDEX Upgrade and global control system-plasma self-entrainment

It is well established that edge localized modes can be entrained to the frequency of applied global magnetic perturbations. These perturbations are delivered to the plasma using the vertical control system field coil currents. These field coils are part of an active control system that is required to maintain the plasma in a steady state. We perform time domain timeseries analysis of natural ELMing when there are no applied perturbations in the ASDEX Upgrade tokamak. We find that the plasma can transition into a state in which the control system field coil currents continually oscillate and are synchronized with oscillations in characteristic plasma parameters such as plasma edge position and total MHD energy. These synchronous oscillations have a one-to-one correlation with the naturally occurring ELMs; the ELMs all occur when the control system coil current is around a specific temporal phase. Large and small ELMs may be distinguished by the amplitude of inward movement of the edge following an ELM. Large ELMs are then found to occur preferentially around a specific temporal phase of the vertical position control coil current. Small ELMs are most likely in antiphase to this. The large and small natural ELMs occur at the opposite extrema of the oscillations in the control system vertical position control coil current. The control system coil current phase may thus provide a useful parameter to order the observed ELM dynamics. We have identified a class of natural ELMing which is a self-entrained state, in which there is a continual non-linear feedback between the global plasma dynamics and the active control system that is intrinsic to the cyclic dynamics of naturally occurring ELMs. Control system-plasma feedback thus becomes an essential component for integration into future models of natural ELM dynamics

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

Background: Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. Objective: To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. Methods: This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. Results: 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). Conclusion: Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure

Low and intermediate-mass close binary evolution and the initial - final mass relation

Using Eggleton's stellar evolution code, we carry out 150 runs of Pop I binary evolution calculations, with the initial primary mass between 1 and 8 solar masses the initial mass ratio between 1.1 and 4, and the onset of Roche lobe overflow (RLOF) at an early, middle, or late Hertzsprung-gap stage. We assume that RLOF is conservative in the calculations, and find that the remnant mass of the primary may change by more than 40 per cent over the range of initial mass ratio or orbital period, for a given primary mass. This is contrary to the often-held belief that the remnant mass depends only on the progenitor mass if mass transfer begins in the Hertzsprung gap. We fit a formula, with an error less than 3.6 per cent, for the remnant (white dwarf) mass as a function of the initial mass of the primary, the initial mass ratio, and the radius of the primary at the onset of RLOF. We also find that a carbon-oxygen white dwarf with mass as low as 0.33 solar masses may be formed if the primary's initial mass is around 2.5 solar masses.Comment: 7 pages for main text, 11 pages for appendix (table A1), 12 figure

Prenatal Opioid Exposure and Intermittent Hypoxemia in Preterm Infants: A Retrospective Assessment

Introduction: Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants. Methods: In order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2 \u3c 80). The secondary outcome measure is the number of severe IH events/week with SpO2 less than 80% (IH-SpO2 \u3c 80). Results: A total of 82 infants with isolated opioid exposure (n = 14) or who were unexposed (n = 68) were included. There were no significant differences in baseline characteristics between opioid exposed and unexposed groups. There was a statistically significant increase of 0.23 (95% CI: 0.03, 0.43, p = 0.03) in mean of the square root of %time-SpO2 \u3c 80. The number of IH-SpO2 \u3c 80 events was higher in the opioid exposed group (mean difference = 2.95, 95% CI: −0.35, 6.25, p-value = 0.08), although statistical significance was not quite attained. Conclusion: This study shows that preterm infants prenatally exposed to opioids have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the opioid exposed group persists beyond the immediate postnatal period

Quantifying neonatal sucking performance: promise of new methods

Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge

Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape

Plasticity of cell migration: a multiscale tuning model

Cell migration underlies tissue formation, maintenance, and regeneration as well as pathological conditions such as cancer invasion. Structural and molecular determinants of both tissue environment and cell behavior define whether cells migrate individually (through amoeboid or mesenchymal modes) or collectively. Using a multiparameter tuning model, we describe how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants—including cell–cell and cell–matrix adhesion, cytoskeletal polarity and stiffness, and pericellular proteolysis—interdependently control migration mode and efficiency. Motile cells integrate variable inputs to adjust interactions among themselves and with the matrix to dictate the migration mode. The tuning model provides a matrix of parameters that control cell movement as an adaptive and interconvertible process with relevance to different physiological and pathological contexts