👤 Kari C Nadeau

Short sleep duration, low physical activity (PA), and sedentary behavior (SB) are associated with negative health outcomes and highly prevalent in adolescents. This study examined changes in the amount and timing of PA and SB following a 1-week sleep extension manipulation in adolescents. Forty-three habitually short-sleeping (≤7 h/night on school days), habitually inactive (<3 hours of regular physical activity per week), and healthy-weight adolescents (16.0 ± 1.24 years, 69.8% female; 86% White) completed a randomized crossover procedure during the school year. Participants slept for 1 week on their typical school schedule (Typical Sleep, TS), and 1 week during which time in bed was extended by ≥1 hour each school night (Sleep Extension, EXT). Home-monitoring of sleep with wrist-worn actigraphy and activity with thigh-worn accelerometer was completed during both conditions. Relationships between sleep, SB, PA, and experimental manipulation were assessed with linear mixed models. SB and light PA (LPA) across the 24 days decreased significantly during EXT compared to TS by 72 minutes and 13.2 minutes, respectively (95% CI: -102, -42, p < .001; 95% CI: -26.4, 0.00, p = .048). SB decreased predominantly between the hours of 18:00-00:00 (-39 minute 95% CI: -54.6, -24, p < .001). There was no significant change in moderate-to-vigorous PA (MVPA) between conditions (p > .05). Increased sleep duration replaced time spent in SB primarily in the evening hours. While LPA decreased primarily in the morning hours, the amount of change was small and likely not clinically significant. Sleep extension did not impact MVPA. Show less

An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19. Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls. Significantly high levels of circulating bacterial DNA were detected in severe COVID-19 cases. In mild COVID-19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID-19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID-19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6. Our results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission. Show less

Balanced chromosomal rearrangements associated with abnormal phenotype are rare events, but may be challenging for genetic counselling, since molecular characterisation of breakpoints is not performed routinely. We used next-generation sequencing to characterise breakpoints of balanced chromosomal rearrangements at the molecular level in patients with intellectual disability and/or congenital anomalies. Breakpoints were characterised by a paired-end low depth whole genome sequencing (WGS) strategy and validated by Sanger sequencing. Expression study of disrupted and neighbouring genes was performed by RT-qPCR from blood or lymphoblastoid cell line RNA. Among the 55 patients included (41 reciprocal translocations, 4 inversions, 2 insertions and 8 complex chromosomal rearrangements), we were able to detect 89% of chromosomal rearrangements (49/55). Molecular signatures at the breakpoints suggested that DNA breaks arose randomly and that there was no major influence of repeated elements. Non-homologous end-joining appeared as the main mechanism of repair (55% of rearrangements). A diagnosis could be established in 22/49 patients (44.8%), 15 by gene disruption ( Paired-end WGS is a valid strategy and may be used for structural variation characterisation in a clinical setting. Show less