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Study Objectives: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls., Methods: SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs., Results: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases., Conclusions: Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) is characterized by recurrent partial to complete upper airway obstructions during sleep, leading to repetitive arousals and oxygen desaturations. Although many OSA biomarkers have been reported individually, only a small subset have been validated through both cross-sectional and intervention studies. We sought to profile serum protein biomarkers in OSA in unbiased high throughput assay., Methods: A highly multiplexed aptamer array (SomaScan) was used to profile 1300 proteins in serum samples from 713 individuals in the Stanford Sleep Cohort, a patient-based registry. Outcome measures derived from overnight polysomnography included Obstructive Apnea Hypopnea Index (OAHI), Central Apnea Index (CAI), 2% Oxygen Desaturation index, mean and minimum oxygen saturation indices during sleep. Additionally, a separate intervention-based cohort of 16 individuals was used to assess proteomic profiles pre- and post-intervention with positive airway pressure., Results: OAHI was associated with 65 proteins, predominantly pathways of complement, coagulation, cytokine signaling, and hemostasis which were upregulated. CAI was associated with two proteins including Roundabout homolog 3 (ROBO3), a protein involved in bilateral synchronization of the pre-Bötzinger complex and cystatin F. Analysis of pre- and post intervention samples revealed IGFBP-3 protein to be increased while LEAP1 (Hepicidin) to be decreased with intervention. An OAHI machine learning classifier (OAHI >=15 vs OAHI<15) trained on SomaScan protein measures alone performed robustly, achieving 76% accuracy in a validation dataset., Conclusions: Multiplex protein assays offer diagnostic potential and provide new insights into the biological basis of sleep disordered breathing., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED)., Methods: This was a retrospective cohort study conducted at British Columbia Children's Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis., Results: There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI., Conclusions: Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: To investigate (1) how many nights of sleep diary entries are required for reliable estimates of five sleep-related outcomes (bedtime, wake time, sleep onset latency [SOL], sleep duration, and wake after sleep onset [WASO]) and (2) the test-retest reliability of sleep diary estimates of school night sleep across 12 weeks., Methods: Data were drawn from four adolescent samples (Australia [n = 385], Qatar [n = 245], United Kingdom [n = 770], and United States [n = 366]), who provided 1766 eligible sleep diary weeks for reliability analyses. We performed reliability analyses for each cohort using complete data (7 days), one to five school nights, and one to two weekend nights. We also performed test-retest reliability analyses on 12-week sleep diary data available from a subgroup of 55 US adolescents., Results: Intraclass correlation coefficients for bedtime, SOL, and sleep duration indicated good-to-excellent reliability from five weekday nights of sleep diary entries across all adolescent cohorts. Four school nights was sufficient for wake times in the Australian and UK samples, but not the US or Qatari samples. Only Australian adolescents showed good reliability for two weekend nights of bedtime reports; estimates of SOL were adequate for UK adolescents based on two weekend nights. WASO was not reliably estimated using 1 week of sleep diaries. We observed excellent test-rest reliability across 12 weeks of sleep diary data in a subsample of US adolescents., Conclusion: We recommend at least five weekday nights of sleep dairy entries to be made when studying adolescent bedtimes, SOL, and sleep duration. Adolescent sleep patterns were stable across 12 consecutive school weeks., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

The Black Queen Hypothesis, recently proposed to explain an evolution of dependency based on gene loss, is gaining ground. This paper focuses on how the evolution of dependency transforms interactions and the community. Using agent-based modeling we suggest that species specializing in the consumption of a common good escape competition and therefore favor coexistence. This evolutionary trajectory could open the way for novel long-lasting interactions and a need to revisit the classically accepted assembly rules. Such evolutionary events also reshape the structure and dynamics of communities, depending on the spatial heterogeneity of the common good production. Let Black be the new black!

Study Objective: This systematic review aims to investigate the association between obstructive sleep apnea (OSA) and diabetic kidney disease (DKD)., Methods: MeSH terms and free text searches were performed on MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception to April 2015. Zetoc and OpenGrey databases were queried for grey literature, and lastly, hand searches were carried out. Study selection and quality assessment were conducted by two authors. One author carried out data extraction, which was checked by other authors. The relationships between apneahypopnea index (AHI), oxygen desaturation index (ODI), time spent under 90% oxygen saturation (%TST < 90), and minimum and mean oxygen saturation (O2) on DKD were examined., Results: Two longitudinal and ten cross-sectional studies were included for our narrative synthesis, and seven studies for meta-analysis. Studies that performed multi-variable analysis demonstrated significant associations between OSA (assessed using either apnea-hypopnea index or ODI) and DKD in type 2 diabetes mellitus (T2DM). This was confirmed by meta-analysis (pooled OR 1.73, 95% CI: 1.13-2.64). There was some evidence to suggest that %TST < 90 may have an association with DKD. There was insufficient evidence to conclude on the relationship between minimum and mean oxygen saturation on DKD. There was no evidence available on the associations between OSA and other respiratory parameters in type 1 diabetes mellitus populations., Conclusions: There is moderate evidence that OSA is associated with DKD in patients with T2DM. Large prospective studies with long-term follow up are needed to assess the possible bi-directional mechanisms between OSA and DKD., (© 2016 Associated Professional Sleep Societies, LLC.)

Context: Obstructive sleep apnea (OSA) has been shown to be associated with type 2 diabetes mellitus (DM). Studies on healthy individuals found that OSA is associated with lower insulin sensitivity. We hypothesized that nocturnal hypoxemia from OSA is associated with poorer glycemia in severely obese DM individuals., Design and Setting: This was a retrospective observational study of 122 non-DM, 126 non-insulin-treated DM, and 35 insulin-treated DM patients. Data were collected on demographic characteristics, body mass index, and comorbidities. An overnight sleep study was performed in all patients, and OSA was defined as an apnea-hypopnea index of ≥5 events/h., Results: There were more males (P = .003) and a lower proportion of white Europeans (P = .010) among DM patients. The prevalence of OSA was 80.1% in DM and 63.1% in non-DM individuals (P = .001). DM individuals also had lower oxygen saturation (O2) (P = .0106), greater percentage of time spent under 90% oxygen saturation (%TST<90%) (P = .0067), and higher apnea-hypopnea index (P = .0085). Regression analysis showed that %TST<90% and minimum O2 saturations were associated with worse hemoglobin A1c results among DM individuals. Every 10% reduction in minimum O2 was associated with a 0.3% increase in HbA1c, whereas a 10% increase in %TST<90% was associated with a 0.2% increase in hemoglobin A1c after adjusting for a range of potential confounders., Conclusion: The high OSA prevalence in DM individuals and a positive relationship between nocturnal hypoxemia and glycemia supports the need to assess correction of hypoxemia as a management strategy for glycemic control.

Introduction: Sleep duration and quality have been associated with obesity. Sleep disturbance has been reported to be associated with stress and depression among non-obese populations, but these relationships have not been previously examined in the obese population. The objective of the current study was to examine the complex associations among sleep disturbance, quality of life, anxiety, and depression in a patient sample with severe obesity., Methods: Two hundred seventy consecutively recruited patients with a mean body mass index (BMI) of 47.0 kg/m² were studied. The correlation coefficient, multiple linear regressions, and structural equation modeling (SEM) analysis were used to evaluate the association between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Hospital Anxiety and Depression Scale (HADS)., Results: The mean (standard deviation; SD) PSQI score was 8.59 (5.11), and mean ESS score was 8.84 (5.79). After controlling for potential confounders, poor sleep quality and excessive daytime sleepiness were found to be significantly associated of all the components of IWQOL-Lite; physical function (β = -0.32, β = -0.27; P < 0.01), self-esteem (β = -0.23, β = -0.30; P < 0.05), sexual-life (β = -0.30, β = -0.35; P < 0.05), public distress (β = -0.39, β = -0.39; P < 0.01), and work (β = -0.26, β = -0.48; P < 0.01). We also found that the PSQI global score had a positive significant association with anxiety (β = 0.29; P = 0.01) and depression (β = 0.31; P = 0.01) components of HADS., Conclusion: Poor sleep quality was strongly associated with mood disturbance and poor quality of life among extremely obese patients. Future interventions are needed to address sleep disturbance to prevent further development of psychological co-morbidity and potentially worsening of obesity among these individuals.

Background: Obstructive sleep apnea (OSA) is a common sleep disorder associated with several adverse health outcomes. Given the close association between OSA and obesity, lifestyle and dietary interventions are commonly recommended to patients, but the evidence for their impact on OSA has not been systematically examined., Objectives: To conduct a systematic review and meta-analysis to assess the impact of weight loss through diet and physical activity on measures of OSA: apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4)., Methods: A systematic search was performed to identify publications using Medline (1948-2011 week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40). The inverse variance method was used to weight studies and the random effects model was used to analyze data., Results: Seven randomized controlled trials (519 participants) showed that weight reduction programs were associated with a decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before-after studies (250 participants) showed a significant decrease in AHI (-12.26 events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after studies (97 participants) with ODI4 as outcome also showed a significant decrease in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43])., Conclusions: Published evidence suggests that weight loss through lifestyle and dietary interventions results in improvements in obstructive sleep apnea parameters, but is insufficient to normalize them. The changes in obstructive sleep apnea parameters could, however, be clinically relevant in some patients by reducing obstructive sleep apnea severity. These promising preliminary results need confirmation through larger randomized studies including more intensive weight loss approaches.

Study Objectives: We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses., Design: Cross-sectional on consecutive recruitment., Setting: Hospital sleep center and pediatric unit., Patients: Forty-three children and adolescents with NC versus 52 age-matched obese children as controls., Interventions: N/A., Measurements and Results: Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence., Conclusions: NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management.

Study Objectives: To provide reference data on sleep duration throughout childhood and explore the demographic characteristics associated with sleep., Design: Population-based prospective longitudinal birth-cohort study., Setting: South-West England, children born in 1991-1992 and followed since birth., Participants: Eleven thousand five hundred children with repeat measures of sleep from birth based on parent-reported questionnaires. Data on daytime and nighttime sleep duration and timings and night awakenings at 8 timepoints from age 6 months to 11 years., Results: Total sleep duration steadily fell from 13 hours and 12 minutes during infancy to 9 hours and 49 minutes at 11 years of age. Compared with earlier studies, the younger children in this cohort slept for a shorter period. The variation in sleep duration was very wide: from 10 to 17 hours in early infancy, narrowing to 8.5 to 11 hours at 11 years. Half of the children at preschool age woke at least once during the night, but frequent waking (> 3 times) peaked in infancy (10% of all infants) and steadily declined in the preschool-aged years. Despite going to bed at the same time, girls slept consistently longer than boys (by 5-10 minutes). Children from low-income families went to bed later and woke up later, but there was little difference in total sleep duration. Children of younger mothers (< 21 years) slept longer, whereas children of older mothers (> 35 years) slept persistently less. Children in larger families tended to go to bed later, as did the minority group of non-White children in the cohort., Conclusions: Given the wide natural variation of sleep in the childhood population, any recommendations on optimal sleep duration at any age must take into account considerable individual variability.

Study Objective: Intentional napping is very common, particularly in China. However, there are limited data regarding its potential health effects. We therefore examined the possible relationship between napping and type 2 diabetes., Design: Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study., Setting: Community-based elderly association in Guangzhou, China., Participants: 19,567 Chinese men and women aged 50 years or older., Measurements and Results: Self-reported frequency of napping was obtained by questionnaire and type 2 diabetes was assessed by fasting blood glucose and/or self-reports of physician diagnosis or treatment. Participants reporting frequent naps (4-6 days/week and daily) were 42% to 52% more likely to have diabetes. The relationships remained essentially unchanged after adjustments were made for demographics, lifestyle and sleep habits, health status, adiposity, and metabolic markers (odds ratio for diabetes 1.36 [95% CI 1.17-1.57] in 4-6 days/week, 1.28 [1.15-1.44] in daily nappers). Similar associations were found between napping and impaired fasting glucose. Removal of those with potential ill health and daytime sleepiness did not alter the observed associations., Conclusions: Napping is associated with elevated prevalence of diabetes and impaired fasting glucose in this older Chinese sample. Our finding suggests that it is less likely that diabetes leads to daytime sleepiness. This raises the possibility that napping may increase the risk of diabetes. Confirmation by longitudinal studies is needed.

Study Objectives: Increasing evidence suggests that alterations in sleep duration are associated with cardiovascular disease (CVD) and mortality. Additionally, sleep disordered breathing (SDB), which is associated with disturbed nighttime sleep and hypoxemia, may be an independent risk factor for CVD. The inflammatory marker, C-reactive protein (CRP), is an important predictor of CVD. We investigated potential associations between circulating CRP, sleep duration, and SDB., Design: Cross-sectional Study., Population: Participants were 907 adults from the Wisconsin Sleep Cohort Study (WSCS)., Measurements and Results: CRP was measured after overnight polysomnography. The relationships between CRP and sleep parameters were evaluated using multiple linear regression with and without controlling for age, sex, and body mass index (BMI) and other potential confounders. CRP was found to be higher for women and had a strong positive correlation with age and BMI. CRP showed a significant positive association with current smoking, waist-hip ratio (WHR), LDL-cholesterol, triglycerides, leptin, and insulin, independent of age, sex, and BMI. Significant independent negative associations for CRP were observed with HDL-cholesterol (HDL), insulin sensitivity (quantitative insulin sensitivity check index [QUICKI]), and hours of exercise. There was a significant positive association between CRP levels and the apnea-hypopnea index (AHI, the measure of SDB), but these relationships were not significant after adjustment for age, sex, and BMI. No significant association between CRP levels and measures of sleep duration (polysomnographic and self-reported) were found., Conclusion: There was no significant association between CRP levels and sleep duration. The lack of an independent association between CRP levels and SDB suggests that the reported relationship between these 2 variables may be primarily driven by their association with obesity.

Objective: To explore whether acute destruction of hypocretin cells in a patient with narcolepsy could be detected and if the course of the disease could be reversed or altered by the use of prednisone for immunosuppression., Design: Case report., Setting: A sleep-clinic population in a tertiary-care hospital., Patient: An 8-year-old boy with a very acute recent (< 2 month) onset of sleepiness., Methods: Sleep studies; fluid-attenuated inversion recovery and gadolinium magnetic resonance imaging studies with a focus on the hypothalamus; examinations of cerebrospinal fluid for cytology, protein, and hypocretin-1 levels; and HLA typing were performed., Intervention: A 3-week regimen of 1 mg x kg(-1) x day(-1) of prednisone was administered in an attempt to modify the course of the disease., Results and Conclusion: Sleep evaluations were consistent with a diagnosis of narcolepsy. Hypocretin-1 was absent in the cerebrospinal fluid, and HLA-DQB1*0602 was present. All other results were within normal limits, and prednisone did not have any noticeable effects. Clinical manifestation of narcolepsy might occur when the hypocretin cell damage is too advanced to be reversible.