Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

Spindles are highly heritable as identified by different spindle detectors.

STUDY OBJECTIVES: Sleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11-16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics. METHODS: We utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability. RESULTS: We found robust evidence to support strong heritability of spindles regardless of detector method (h2 > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results. CONCLUSIONS: The sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.

Increased Incidence but Lack of Association Between Cardiovascular Risk Factors in Adults Born Preterm.

Preterm birth incurs an increased risk of early cardiovascular events and death. In the general population, cardiovascular risk factors cluster in the context of inflammation and oxidative stress. Whether this also occurs in young adults born preterm is unknown. We analyzed 101 healthy young adults (ages 18-29) born preterm (≤29 weeks of gestation) and 105 full-term controls, predominantly (90%) white. They underwent a comprehensive clinical and biological evaluation, including measurement of blood pressure, lung function (spirometry), glucose metabolism (fasting glucose, glycated hemoglobin, and oral glucose tolerance test), as well as biomarkers of inflammation and oxidative stress. Individuals born preterm were at higher risk than those born full-term of stage ≥1 hypertension (adjusted odds ratio, 2.91 [95% CI, 1.51-5.75]), glucose intolerance (adjusted odds ratio, 2.22 [95% CI, 1.13-4.48]), and airflow limitation (adjusted odds ratio, 3.47 [95% CI, 1.76-7.12]). Hypertension was strongly associated with adiposity and with glucose intolerance in participants born full-term but not in those born preterm. We did not find any group difference in levels of biomarkers of inflammation and oxidative stress. In individuals born preterm, inflammation, and oxidative stress were not related to hypertension or glucose intolerance but were associated with adiposity. In those born preterm, cardiovascular risk factors were not related to each other suggesting different pathophysiological pathways leading to the development of cardiovascular risk following preterm birth. Clinicians should consider screening for these abnormalities irrespectively of other risk factors in this at-risk population. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03261609.

Doxorubicin treatments induce significant changes on the cardiac autonomic nervous system in childhood acute lymphoblastic leukemia long-term survivors.

AIMS: Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system. METHODS AND RESULTS: A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed. CONCLUSION: Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.

A sleep spindle detection algorithm that emulates human expert spindle scoring.

BACKGROUND: Sleep spindles are a marker of stage 2 NREM sleep that are linked to learning & memory and are altered by many neurological diseases. Although visual inspection of the EEG is considered the gold standard for spindle detection, it is time-consuming, costly and can introduce inter/ra-scorer bias. NEW METHOD: Our goal was to develop a simple and efficient sleep-spindle detector (algorithm #7, or 'A7') that emulates human scoring. 'A7' runs on a single EEG channel and relies on four parameters: the absolute sigma power, relative sigma power, and correlation/covariance of the sigma band-passed signal to the original EEG signal. To test the performance of the detector, we compared it against a gold standard spindle dataset derived from the consensus of a group of human experts. RESULTS: The by-event performance of the 'A7' spindle detector was 74% precision, 68% recall (sensitivity), and an F1-score of 0.70. This performance was equivalent to an individual human expert (average F1-score = 0.67). COMPARISON WITH EXISTING METHOD(S): The F1-score of 'A7' was 0.17 points higher than other spindle detectors tested. Existing detectors have a tendency to find large numbers of false positives compared to human scorers. On a by-subject basis, the spindle density estimates produced by A7 were well correlated with human experts (r2 = 0.82) compared to the existing detectors (average r2 = 0.27). CONCLUSIONS: The 'A7' detector is a sensitive and precise tool designed to emulate human spindle scoring by minimizing the number of 'hidden spindles' detected. We provide an open-source implementation of this detector for further use and testing.

Endothelial Colony-Forming Cells in Young Adults Born Preterm: A Novel Link Between Neonatal Complications and Adult Risks for Cardiovascular Disease.

BACKGROUND: Preterm birth is linked to cardiovascular risks and diseases. Endothelial progenitor cells play a critical role in vascular development and repair. Cord blood endothelial progenitor cells of preterm-born infants, especially endothelial colony-forming cells (ECFC), show enhanced susceptibility to prematurity-related pro-oxidant stress. Whether ECFC dysfunction is present in adulthood following preterm birth is unknown. METHODS AND RESULTS: This cross-sectional observational study includes 55 preterm-born (≤29 gestational weeks) young adults (18-29 years old, 38% male) and 55 sex- and age-matched full-term controls. ECFC were isolated from peripheral blood; cell proliferative and vascular cord formation capacities were assessed in vitro. Daytime systolic blood pressure was higher, whereas glucose tolerance and body mass index were lower in preterm-born subjects. ECFC colonies grew in culture for 62% of full-term- and 58% of preterm-born participants. Preterm-born participants have formed ECFC colonies later in culture and have reduced proliferation compared with controls. Only in preterm-born individuals, we observed that the later the ECFC colony grows in culture, the worse was overall ECFC function. In addition, in preterms, elevated systolic blood pressure significantly correlated with reduced ECFC proliferation (rS=-0.463; P=0.030) and numbers of branches formed on matrigel (rS=-0.443; P=0.039). In preterm-born subjects, bronchopulmonary dysplasia was associated with impaired ECFC function, whereas exposure to antenatal steroids related to better ECFC function. CONCLUSIONS: This study is the first to examine ECFC in preterm-born adults and to demonstrate ECFC dysfunction compared with full-term controls. In the preterm-born group, ECFC dysfunction was associated with bronchopulmonary dysplasia, the major prematurity-related neonatal morbidity, and with increased systolic blood pressure into adulthood.