Cerebrovascular responses to a 90° tilt in healthy neonates.

BACKGROUND: Tilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates. METHODS: We performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt. RESULTS: rcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters. CONCLUSION: A 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations. IMPACT: Healthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt. We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts. No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.

Sociodemographic profile associated with congenital heart disease among infants <1 year old.

PURPOSE: Congenital heart disease affects thousands of newborns each year in the United States. Previous United States-based research has explored how sociodemographic factors may impact health outcomes in infants with congenital heart disease; however, their impact on the incidence of congenital heart disease is unclear. We explored the sociodemographic profile related to congenital heart disease to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with congenital heart disease will encourage implementation of potential preventative measures. DESIGN AND METHODS: We conducted a secondary analysis of longitudinally collected data comparing 39 infants with congenital heart disease and 30 healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with congenital heart disease and healthy controls. RESULTS: We found a statistically significant difference in maternal education between our 2 groups of infants (p = 0.004). CONCLUSION: Maternal education was associated with congenital heart disease. Future studies are needed to further characterize sociodemographic factors that may predict and impact the incidence of congenital heart disease and to determine possible interventions that may help decrease health disparities regarding the incidence of congenital heart disease. PRACTICE IMPLICATIONS: Understanding the associations between maternal sociodemographic factors and infant congenital heart disease would allow clinicians to identify mothers at higher risk of having an infant with congenital heart disease.

A pilot study: Comparing a novel noninvasive measure of cerebrovascular stability index with an invasive measure of cerebral autoregulation in neonates with congenital heart disease.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI's correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Sociodemographic Profile Associated with Congenital Heart Disease among Infants Less than 1 Year Old.

Background: Congenital heart disease (CHD) affects thousands of newborns each year in the United States (US). Infants born with CHD have an increased risk of adverse health outcomes compared to healthy infants. These outcomes include, but are not limited to, neurodevelopmental, surgical, and mortality-related outcomes. Previous US-based research has explored how sociodemographic factors may impact these health outcomes in infants with CHD; however, their impact on the risk of CHD is unclear. This study aims to explore the sociodemographic profile related to CHD to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with CHD will encourage policy change and the implementation of preventative measures. Methods: This study is a secondary analysis of longitudinally collected data. We compared infants with CHD and healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with CHD and healthy controls. Results: We obtained sociodemographic factors from 30 healthy control infants and 39 infants with CHD. We found a statistically significant difference in maternal education between our 2 groups of infants (p=0.004). Conclusion: Maternal education is associated with CHD. Future studies are needed to further characterize sociodemographic factors that may predict and impact the risk of CHD and to determine possible interventions that may help decrease health disparities regarding the risk of CHD.

Harmonization of Multi-Center Diffusion Tensor Tractography in Neonates with Congenital Heart Disease: Optimizing Post-Processing and Application of ComBat.

Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researcher's ability to harmonize data acquired under different conditions or using different clinical populations. 2) The general lack of objective guidelines for dealing with anatomically abnormal anatomy and pathology. Often, subjects are excluded due to subjective criteria, or due to pathology that could be informative to the final analysis, leading to the loss of reproducibility and statistical power. This proves to be a barrier in the analysis of large multi-center studies and is a particularly salient problem given the relative scarcity of neonatal imaging data. We provide an objective, data-driven, and semi-automated neonatal processing pipeline designed to harmonize compartmentalized variant data acquired under different parameters. This is done by first implementing a search space reduction step of extracting the along-tract diffusivity values along each tract of interest, rather than performing whole-brain harmonization. This is followed by a data-driven outlier detection step, with the purpose of removing unwanted noise and outliers from the final harmonization. We then use an empirical Bayes harmonization algorithm performed at the along-tract level, with the output being a lower dimensional space but still spatially informative. After applying our pipeline to this large multi-site dataset of neonates and infants with congenital heart disease (n= 398 subjects recruited across 4 centers, with a total of n=763 MRI pre-operative/post-operative time points), we show that infants with single ventricle cardiac physiology demonstrate greater white matter microstructural alterations compared to infants with bi-ventricular heart disease, supporting what has previously been shown in literature. Our method is an open-source pipeline for delineating white matter tracts in subject space but provides the necessary modular components for performing atlas space analysis. As such, we validate and introduce Diffusion Imaging of Neonates by Group Organization (DINGO), a high-level, semi-automated framework that can facilitate harmonization of subject-space tractography generated from diffusion tensor imaging acquired across varying scanners, institutions, and clinical populations. Datasets acquired using varying protocols or cohorts are compartmentalized into subsets, where a cohort-specific template is generated, allowing for the propagation of the tractography mask set with higher spatial specificity. Taken together, this pipeline can reduce multi-scanner technical variability which can confound important biological variability in relation to neonatal brain microstructure.

Factor Analysis of the Einstein Neonatal Neurobehavioral Assessment Scale in Infants with Congenital Heart Disease and Healthy Controls.

Background: Administration of the Einstein Neonatal Neurobehavioral Assessment Scale (ENNAS) can be time-consuming, and items can be highly correlated. We aimed to determine: (1) its factor analytic structure; (2) the validity of the factor structure; and (3) the associations of physiologic measures with factor scores. Methods: A factor analysis reduced 21 ENNAS items into 5 factors in 57 congenital heart disease (CHD) and 35 healthy infants. Multiple linear regressions examined the association of factor scores with group, gestational age, and physiologic variables. Results: 5-factor solution: 1 (Orienting Reflex), 2 (Extensor Axial Tone), 3 (Primitive Reflexes), 4 (Flexor Tone), 5 (Reflexive Tone Around Extremity Joints). Moderate to strong evidence supported: face, discriminant, and construct validity of these factors, with Factor 2 having the strongest. Conclusions: Components of Factor 2 may provide similar information about neonatal development, thus reducing the time for and burden of administration for researchers and clinicians.

Factors Associated With Gastrostomy Tube Complications in Infants With Congenital Heart Disease.

INTRODUCTION: Children with congenital heart disease (CHD) often experience feeding intolerance due to aspiration, inability to tolerate feed volume, or reflux within the first few months of life, requiring a surgically placed gastrostomy tube (GT) for durable enteral access. However, complications such as GT dislodgement, cellulitis, and leakage related to GT use are common. GT-related complications can lead to unscheduled pediatric surgery clinic or emergency room (ER) visits, which can be time consuming for the family and increase overall healthcare costs. We sought to identify factors associated with GT complications within 2 wk after GT surgery and 1-y after discharge home following GT placement in infants with CHD. METHODS: We performed a retrospective cohort study using the Society of Thoracic Surgeons database and electronic medical records from a tertiary children's hospital. We identified infants <1 y old underwent CHD surgery followed by GT surgery between September 2013-August 2018. Demographics, pre-operative feeding regimen, comorbidities, and GT-related utilization were measured. Postoperative GT complications (e.g., GT cellulitis, leakage, dislodgement, obstruction, and granulation tissue) within 2 wk after the GT surgery and an unplanned pediatric surgery clinic or ER visit within 1-y after discharge home were captured. Bivariate comparisons and multivariable logistic regression evaluated factors associated with GT complications and unplanned clinic or ER visits. A Kaplan-Meier failure curve examined the timing of ER/clinic visits. RESULTS: Of 152 infants who underwent CHD then GT surgeries, 66% (N = 101) had postoperative GT complications. Overall, 83 unscheduled clinic visits were identified after discharge, with 37% (N = 31) due to concerns about granulation tissue. Of 137 ER visits, 48% (N = 66) were due to accidental GT dislodgement. Infants who were hospitalized for ≥2 wk after GT surgery had more complications than those discharged home within 2 wk of the GT surgery (40.6% versus 15.7%, P = 0.002). Infants receiving oral nutrition before CHD surgery (38.6% versus 60%, P=<0.001) or with single ventricle defects (19.8% versus 37.3%, P = 0.02) had fewer GT complications. After adjusting for type of cardiac anomaly, infants receiving oral nutrition prior to CHD surgery had a decreased likelihood of GT complications (odds ratio OR 0.46; 95% confidence intervals CI:0.23-0.93). A Kaplan-Meier failure curve demonstrated that 50% of the cohort experienced a complication leading to an unscheduled ER/clinic visit within 6 mo after discharge. CONCLUSIONS: Unplanned visits to the ER or pediatric surgery clinic occur frequently for infants with CHD requiring a surgically placed GT. Oral feedings before cardiac surgery associated with fewer GT complications. Prolonged hospitalization associated with more GT complications. Optimizing outpatient care and family education regarding GT maintenance may reduce unscheduled visits for this high-risk, device-dependent infant population.

Preoperative Care of Neonates With Congenital Heart Disease.

Congenital heart disease (CHD) is one of the most common types of birth defects, with 40,000 newborns diagnosed yearly in the United States. This article describes: (1) four common heart defects seen in neonatal intensive care units, (2) the typical medical/nursing care of these neonates, and (3) common surgical management for the defects. Hypoplastic left heart syndrome, dextro-transposition of the great arteries, tetralogy of Fallot, and pulmonary atresia with intact ventricular septum are four common types of CHD requiring NICU admission. Knowledge of these defects will help nurses to appropriately manage and treat neonates with these types of CHD.

Source of Rate Acceleration for Carbocation Cyclization in Biomimetic Supramolecular Cages.

The results of quantum chemical and molecular dynamics calculations reveal that polyanionic gallium-based cages accelerate cyclization reactions of pentadienyl alcohols as a result of substrate cage interactions, preferential binding of reactive conformations of substrate/H3O+ pairs, and increased substrate basicity. However, the increase in basicity dominates. Experimental structure-activity relationship studies in which the metal vertices and overall charge of the cage are varied confirm the model derived via calculations.

Association of Cerebrovascular Stability Index and Head Circumference Between Infants With and Without Congenital Heart Disease.

Congenital heart disease (CHD) is a common birth defect in the United States. CHD infants are more likely to have smaller head circumference and neurodevelopmental delays; however, the cause is unknown. Altered cerebrovascular hemodynamics may contribute to neurologic abnormalities, such as smaller head circumference, thus we created a novel Cerebrovascular Stability Index (CSI), as a surrogate for cerebral autoregulation. We hypothesized that CHD infants would have an association between CSI and head circumference. We performed a prospective, longitudinal study in CHD infants and healthy controls. We measured CSI and head circumference at 4 time points (newborn, 3, 6, 9 months). We calculated CSI by subtracting the average 2-min sitting from supine cerebral oxygenation (rcSO2) over three consecutive tilts (0-90°), then averaged the change score for each age. Linear regressions quantified the relationship between CSI and head circumference. We performed 177 assessments in total (80 healthy controls, 97 CHD infants). The average head circumference was smaller in CHD infants (39.2 cm) compared to healthy controls (41.6 cm) (p < 0.001) and head circumference increased by 0.27 cm as CSI improved in the sample (p = 0.04) overall when combining all time points. Similarly, head circumference increased by 0.32 cm as CSI improved among CHD infants (p = 0.04). We found CSI significantly associated with head circumference in our sample overall and CHD infants alone, which suggests that impaired CSI may affect brain size in CHD infants. Future studies are needed to better understand the mechanism of interaction between CSI and brain growth.

Public Health Emergency Response Leadership Training: A Qualitative Assessment of Existing Educational Opportunities and Perceived Facilitators, Barriers, and Priorities in Professional Development.

OBJECTIVE: We aimed to understand the current training environment for developing public health emergency response leaders and highlight facilitators and barriers in accessing targeted training. DESIGN: We designed 4 focus groups to gather organizational perspectives on public health emergency response leadership development. Discussions were recorded, transcribed, coded, and analyzed to synthesize key themes. SETTING: Focus groups were convened at the 2019 Preparedness Summit (March 27-28) in St Louis, Missouri. PARTICIPANTS: Twenty-three public health professionals from 9 Public Health Emergency Preparedness (PHEP) Cooperative Agreement award recipient jurisdictions and 12 local health departments participated. MAIN OUTCOME MEASURES: We examined the current availability, relevance, specificity, and utility of educational content and delivery modalities. Facilitators and barriers were identified as opportunities to improve training access. RESULTS: Generic emergency management training is considered important and widely available but with limited application in public health practice. Existing leadership training opportunities in public health emergency response are limited and not widely known. While organizational support and accessible training facilitate participation, resource constraints (ie, funding, time, and staff) exist as key barriers. In addition, frequent staff turnover and attrition that result in loss of institutional knowledge likely hinder effective public health emergency responses. CONCLUSION: Effective public health emergency response depends on capable leaders not only well versed in specialized technical disciplines and practices but also familiar with-or preferably fluent in-emergency management principles and functions. This study demonstrated that well-aimed training strategies and organizational planning are essential in developing public health emergency response leaders. Specifically, leadership development may accrue considerable benefit from a standardized training curriculum. In addition, scalable training programs developed through public, private, and academic partnerships may lessen resource demands on individual organizations to facilitate training access. Finally, training practicums (eg, mentoring, shadowing) may provide opportunities to facilitate active learning and preserve institutional knowledge through leadership transitions.

Factors Impacting Long-Term Gastrostomy Tube Dependence in Infants with Congenital Heart Disease.

BACKGROUND: Infants with congenital heart disease (CHD) often experience oral feeding intolerance requiring gastrostomy (GT). Complications related to GT use are common. The study aim was to identify factors associated with continued GT use at one-year. METHODS: A retrospective cohort study was performed at a tertiary children's hospital using the Society of Thoracic Surgeons database and patients' electronic medical record. Infants <1-year with CHD who underwent cardiac and GT surgery between January 2014-October 2019 were identified. Patient demographics, preoperative feeding, clinical variables, and GT use at one-year was evaluated. A separate cohort discharged with a nasogastric tube (NGT) was identified for longitudinal comparisons. RESULTS: Of 137 infants who received a GT, 115 (84%) continued using their GT at one-year. Factors associated with continued GT use included lower median percent of goal oral feeding before GT placement (0% IQR 0-6.5 versus 3.7% IQR 0-31), prolonged hospitalization after GT placement (36% versus 14%, P-value = 0.048), and failure to take oral feeds at discharge (69% versus 27%, P-value <0.001). There was no difference in demographics or clinical comorbidities between groups. Clinic/emergency room visits for GT complications were common (72%). Eight infants discharged with a NGT did not require GT placement. CONCLUSIONS: Patients with CHD tolerating minimal oral nutrition before GT placement, prolonged hospitalization after GT, and difficulty with oral feeds at discharge were more likely to use their GT at 1-year. Outpatient NGT feeding is feasible for select infants with CHD. Efforts to optimize care for this complex, device-dependent population are warranted to minimize risks and facilitate family engagement for long-term care.

Impact of COVID-19 on Pediatric Clinical Research.

PURPOSE: Many public institutions and settings have taken action to limit exposure to and slow the spread of the novel coronavirus (COVID-19). We sought to characterize the impact of stay-at-home orders on our study of cerebral autoregulation and its association with developmental delays in infants with congenital heart disease compared with healthy controls. DESIGN AND METHODS: We calculated the number of participants recruited (i.e., not enrolled in the study) and assessed (i.e., currently enrolled) before March 2020 (pre-COVID-19) and the number of participants that we could not recruit or assess between March and July 2020 (missed due to COVID-19), separately for congenital heart disease and healthy control infants, in reference to the impacts of COVID-19. We used negative binomial regressions to determine incidence rate ratios which compared participants recruited and assessed pre-COVID-19 and missed due to COVID-19. RESULTS: Recruitment and assessments significantly decreased following the pandemic, i.e., participants were more likely to be recruited or be assessed pre-COVID-19 compared to during the pandemic. Study participants were 3.3 times as likely to have assessments performed pre-COVID-19 compared to during the COVID-19 pandemic (p < 0.001). CLINICAL IMPLICATIONS: Clinical research teams may consider making protocol modifications such as virtual visits or video recordings explaining the study, for example, to adjust to the restrictions caused by COVID-19. CONCLUSION: The COVID-19 pandemic drastically reduced recruitment and assessments completed in our study. Study teams will need to continue to modify procedures for recruitment and assessments that align with COVID-19 regulations to facilitate research progress during the pandemic.

HCV Proteins Modulate the Host Cell miRNA Expression Contributing to Hepatitis C Pathogenesis and Hepatocellular Carcinoma Development.

Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at the surface of HCV particles. Non-structural (NS) proteins consist of NS1, NS2, NS3, NS4A, NS4B, NS5a, and NS5b and have a variable function in HCV RNA replication and particle assembly. Recent findings evidenced the capacity of HCV virus to modulate host cell factors to create a favorable environment for replication. Indeed, increasing evidence has indicated that the presence of HCV is significantly associated with aberrant miRNA expression in host cells, and HCV structural and non-structural proteins may be responsible for these alterations. In this review, we summarize the recent findings on the role of HCV structural and non-structural proteins in the modulation of host cell miRNAs, with a focus on the molecular mechanisms responsible for the cell re-programming involved in viral replication, immune system escape, as well as the oncogenic process. In this regard, structural and non-structural proteins have been shown to modulate the expression of several onco-miRNAs or tumor suppressor miRNAs.

Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls.

OBJECTIVE: Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. METHODS: We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). RESULTS: Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (ß = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (ß = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (ß = -1.5; 95%CI = -2.95, -0.05; p = 0.04). CONCLUSION: CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

Near-Infrared Spectroscopy: Clinical Use in High-Risk Neonates.

In this review, we describe the near-infrared spectroscopy (NIRS) technology and its clinical use in high-risk neonates in critical care settings. We searched databases (e.g., PubMed, Google Scholar, EBSCOhost) to find studies describing the use of NIRS on critically ill and high-risk neonates. Near-infrared spectroscopy provides continuous noninvasive monitoring of venous oxygen saturation. It uses technology similar to pulse oximetry to measure the oxygen saturation of hemoglobin in a tissue bed to describe the relative delivery and extraction of oxygen. Near-infrared spectroscopy can be a valuable bedside tool to provide clinicians indirect evidence of perfusion. It may prompt early interventions that promote oxygen delivery, which can improve high-risk neonatal outcomes.

The Use of Near-Infrared Spectroscopy (NIRS) to Measure Cerebral Oxygen Saturation During Body Position Changes on Infants Less than One Year Old.

OBJECTIVE: To describe the state of the literature for near-infrared spectroscopy (NIRS) to measure cerebral oxygen saturation during body position changes on infants <1 year old. INTRODUCTION: Although regional cerebral oxygen saturation is commonly used in critically ill populations, it is not usual practice to tailor care based on differences in the cerebral oxygen saturation during measurements in different body positions. We believe that alterations in cerebral oxygen saturation during position changes can also inform clinicians regarding brain health, such as the regulation of brain blood flow. INCLUSION CRITERIA: We included studies in infants <1 year old; who had cerebral oxygen saturation measured in varying positions (e.g. supine versus side-lying). METHODS: On March 30, 2019, we searched Medline, Embase, Cochrane CENTRAL, CINAHL, and Web of Science for studies written in English with no restriction on publication dates. We selected studies that involved infants <1 year old and measured cerebral oxygen saturation during varying body positions. RESULTS: We found 24 primary studies on 694 infants. The authors investigated whether brain oxygen saturation was influenced by body position. A majority of the studies found a statistically significant difference between cerebral oxygen saturation in various body positions. CONCLUSIONS: More research needs to be performed on variations in brain oxygen saturation during body position changes and the correlation with outcomes. Knowledge of brain oxygen saturation can provide clinicians an understanding of the infant's brain health. Healthcare providers may adapt care specifically to improve brain health with NIRS-based brain oxygen saturation monitoring.

Synthesis, Characterization, and Reactivity of Complex Tricyclic Oxonium Ions, Proposed Intermediates in Natural Product Biosynthesis.

Reactive intermediates frequently play significant roles in the biosynthesis of numerous classes of natural products although the direct observation of these biosynthetically relevant species is rare. We present here direct evidence for the existence of complex, thermally unstable, tricyclic oxonium ions that have been postulated as key reactive intermediates in the biosynthesis of numerous halogenated natural products from Laurencia species. Evidence for their existence comes from full characterization of these oxonium ions by low-temperature NMR spectroscopy supported by density functional theory (DFT) calculations, coupled with the direct generation of 10 natural products on exposure of the oxonium ions to various nucleophiles.

Structure Determination of a Chloroenyne from Laurencia majuscula Using Computational Methods and Total Synthesis.

Despite numerous advances in spectroscopic methods through the latter part of the 20th century, the unequivocal structure determination of natural products can remain challenging, and inevitably, incorrect structures appear in the literature. Computational methods that allow the accurate prediction of NMR chemical shifts have emerged as a powerful addition to the toolbox of methods available for the structure determination of small organic molecules. Herein, we report the structure determination of a small, stereochemically rich natural product from Laurencia majuscula using the powerful combination of computational methods and total synthesis, along with the structure confirmation of notoryne, using the same approach. Additionally, we synthesized three further diastereomers of the L. majuscula enyne and have demonstrated that computations are able to distinguish each of the four synthetic diastereomers from the 32 possible diastereomers of the natural product. Key to the success of this work is to analyze the computational data to provide the greatest distinction between each diastereomer, by identifying chemical shifts that are most sensitive to changes in relative stereochemistry. The success of the computational methods in the structure determination of stereochemically rich, flexible organic molecules will allow all involved in structure determination to use these methods with confidence.

Cerebral Autoregulation in Neonates With and Without Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is a leading birth defect in the United States, affecting about 40 000 neonates each year. Despite efforts to prevent developmental delays, many children with CHD have neurological deficits that last into adulthood, influencing employability, self-care, and quality of life. OBJECTIVE: To determine if neonates with CHD have impaired cerebral autoregulation and poorer neurodevelopmental outcomes compared with healthy controls. METHODS: A total of 44 full-term neonates, 28 with CHD and 16 without, were enrolled in the study. Inclusion criteria included confirmed diagnosis of CHD, stable hemodynamic status, and being no more than 12 days old. Exclusion criteria included intraventricular hemorrhage and intubation. Cerebral autoregulation was determined by measuring regional cerebral oxygenation during a postural change. The Einstein Neonatal Neurobehavioral Assessment Scale was used to measure overall neurodevelopmental outcomes (motor, visual, and auditory functions). RESULTS: Of the 28 neonates with CHD, 8 had single-ventricle physiology. A χ2 analysis indicated no significant difference in impaired cerebral autoregulation between neonates with CHD and controls (P = .38). Neonates with CHD had lower regional cerebral oxygenation than did neonates without CHD (P < .001). Regression analyses with adjustments for cerebral autoregulation indicated that neonates with CHD had poorer total neurodevelopmental outcomes scores (ß = 9.3; P = .02) and motor scores (ß = 7.6; P = .04). CONCLUSION: Preoperative neonates with CHD have poorer developmental outcomes and more hypoxemia than do controls.