Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants:A Systematic Review

Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants

Neonatal Hemoglobin Levels in Preterm Infants Are Associated with Early Neurological Functioning

Background: Neonatal anemia may compromise oxygen transport to the brain. The effects of anemia and cerebral oxygenation on neurological functioning in the early neonatal period are largely unknown. Objective: This study aimed to determine the association between initial hemoglobin levels (Hb) and early neurological functioning in preterm infants by assessing their general movements (GMs). Methods: A retrospective analysis of prospectively collected data on preterm infants born before 32 weeks of gestation was conducted. We excluded infants with intraventricular hemorrhage > grade II. On day 8, we assessed infants' GMs, both generally as normal/abnormal and in detail using the general movement optimality score (GMOS). We measured cerebral tissue oxygen saturation (r(c)SO(2)) on day 1 using near-infrared spectroscopy. Results: We included 65 infants (median gestational age 29.9 weeks [IQR 28.2-31.0]; median birth weight 1,180 g [IQR 930-1,400]). Median Hb on day 1 was 10.3 mmol/L (range 4.2-13.7). Lower Hb on day 1 was associated with a higher risk of abnormal GMs (OR = 2.3, 95% CI: 1.3-4.1) and poorer GMOSs (B = 0.9, 95% CI: 0.2-1.7). Hemoglobin strongly correlated with r(c)SO(2) (rho = 0.62, p < 0.01). Infants with lower r(c)SO(2) values tended to have a higher risk of abnormal GMs (p = 0.06). After adjusting for confounders, Hb on day 1 explained 44% of the variance of normal/abnormal GMs and r(c)SO(2) explained 17%. Regarding the explained variance of the GMOS, this was 25% and 16%, respectively. Conclusions: In preterm infants, low Hb on day 1 is associated with impaired neurological functioning on day 8, which is partly explained by low cerebral oxygenation

Noise Minimization in Cell-Free Gene Expression

Biochemical reactions that involve small numbers of molecules are accompanied by a degree of inherent randomness that results in noisy reaction outcomes. In synthetic biology, the ability to minimize noise particularly during the reconstitution of future synthetic protocells is an outstanding challenge to secure robust and reproducible behavior. Here we show that by encapsulation of a bacterial cell-free gene expression system in water-in-oil droplets, in vitro-synthesized MazF reduces cell-free gene expression noise &gt;2-fold. With stochastic simulations we identify that this noise minimization acts through both increased degradation and the autoregulatory feedback of MazF. Specifically, we find that the expression of MazF enhances the degradation rate of mRNA up to 18-fold in a sequence-dependent manner. This sequence specificity of MazF would allow targeted noise control, making it ideal to integrate into synthetic gene networks. Therefore, including MazF production in synthetic biology can significantly minimize gene expression noise, impacting future design principles of more complex cell-free gene circuits.</p

Depressive Symptoms and the Experience of Pleasure in Daily Life:An Exploration of Associations in Early and Late Adolescence

Although loss of pleasure (i.e., anhedonia) is one of the two core symptoms of depression, very little research has examined the relation between depressive symptoms and the experience of pleasure in daily life. This exploratory study in two population-based adolescent samples aimed to examine how depressive symptoms and anhedonia specifically were related to (1) the proportion and intensity of positive events, (2) mean and variability of positive affect (PA), (3) reactivity to positive events, and (4) reactivity to PA (i.e., whether PA elicits positive events). We used Experience Sampling to measure positive events and PA several times a day during 6 to 14 days in early (N = 284) and late (N = 74) adolescents. Results showed that depressive symptoms were related to a lower proportion and intensity of positive events, lower mean PA, and higher variability in PA regardless of sex and stage of adolescence. No clear evidence was found for differential reactivity to positive events or to PA. Anhedonia was not associated with most daily life experiences of pleasure. Our findings, though preliminary, suggest that although adolescents with many depressive symptoms experience less positive events and lower PA, they are able to enjoy pleasurable events to the same extent as individuals with fewer depressive symptoms

Measuring cerebrovascular autoregulation in preterm infants using near-infrared spectroscopy: an overview of the literature

Introduction: The preterm born infant’s ability to regulate its cerebral blood flow (CBF) is crucial in preventing secondary ischemic and hemorrhagic damage in the developing brain. The relationship between arterial blood pressure (ABP) and CBF estimates, such as regional cerebral oxygenation as measured by near-infrared spectroscopy (NIRS), is an attractive option for continuous non-invasive assessment of cerebrovascular autoregulation. Areas covered: The authors performed a literature search to provide an overview of the current literature on various current clinical practices and methods to measure cerebrovascular autoregulation in the preterm infant by NIRS. The authors focused on various aspects: Characteristics of patient cohorts, surrogate measures for cerebral perfusion pressure, NIRS devices and their accompanying parameters, definitions for impaired cerebrovascular autoregulation, methods of measurements and clinical implications. Expert commentary: Autoregulation research in preterm infants has reported many methods for measuring autoregulation using different mathematical models, signal processing and data requirements. At present, it remains unclear which NIRS signals and algorithms should be used that result in the most accurate and clinically relevant assessment of cerebrovascular autoregulation. Future studies should focus on optimizing strategies for cerebrovascular autoregulation assessment in preterm infants in order to develop autoregulation-based cerebral perfusion treatment strategies

Probing the hydrothermal system of the Chicxulub impact crater

The ~180-km-diameter Chicxulub peak-ring crater and ~240-km multiring basin, produced by the impact that terminated the Cretaceous, is the largest remaining intact impact basin on Earth. International Ocean Discovery Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drilled to a depth of 1335 m below the sea floor into the peak ring, providing a unique opportunity to study the thermal and chemical modification of Earth’s crust caused by the impact. The recovered core shows the crater hosted a spatially extensive hydrothermal system that chemically and mineralogically modified ~1.4 × 105 km3 of Earth’s crust, a volume more than nine times that of the Yellowstone Caldera system. Initially, high temperatures of 300° to 400°C and an independent geomagnetic polarity clock indicate the hydrothermal system was long lived, in excess of 106 years

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Near-infrared spectroscopy to detect absence of cerebrovascular autoregulation in preterm infants

Objective: Our aim was to explore clinical parameters that might predict the absence of cerebrovascular autoregulation (CAR) assessed by a negative relationship between mean arterial blood pressure (MABP) and fractional tissue oxygen extraction (FTOE) as measured by near-infared spectroscopy (NIRS) in preterm infants. Methods: We included preterm infants (gestational age (GA) Results: Ten (40%) out of 25 infants (median GA 29.1 weeks, range 25.4-31.7, birth weight 1245 g, 560-1780) had a statistically significant negative correlation between MABP and FTOE (rho -0.432 to -0.156), suggesting the absence of CAR. None of the clinical variables predicted the absence of CAR. Conclusions: We were unable to predict the absence of CAR in terms of clinical variables. Nevertheless, we found a statistically significant negative correlation between MABP and FTOE using NIRS, suggesting the absence of CAR in almost half of the preterm infants studied. Significance: NIRS could be a helpful tool to assess the presence or absence of CAR. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved