E-cigarettes can help smokers quit, but how e-cigarettes used for tobacco smoking cessation impact sleep is still unclear. The primary objective was to evaluate the effect of e-cigarettes for smoking abstinence on sleep quality. Secondary objectives included subscales of sleep quality. We conducted a secondary analysis of the Efficacy, Safety, and Toxicology of electronic nicotine delivery systems for smoking cessation (ESTxENDS) randomized controlled trial, which included adult smokers in Switzerland (5 sites, 7.2018-6.2021). The intervention group received free e-cigarettes and e-liquids over 6 months plus standard-of-care smoking-cessation counseling (SOC); the control group received SOC alone. The primary outcome was overall self-reported sleep quality at 6 months, measured by the Pittsburgh Sleep Quality Index (PSQI). We considered a minimal clinically important difference (MCID) of 2.5-5. Secondary outcomes included PSQI subscales. We used adjusted linear regressions with inverse probability of attrition weights (IPAW). ESTxENDS included 1246 participants. Of these, 831 participants completed the PSQI at follow-up. For the primary outcome, there was no significant difference in PSQI score between groups (b=-0.20, p=.256, adjusted analyses with IPAW). For PSQI subscales, only sleep efficiency was significantly better in the intervention group (b=1.87, p=.018), below MCID. E-cigarettes added to SOC for tobacco smoking abstinence did not significantly alter participant's self-reported sleep quality compared to SOC alone. Clinicians can inform patients willing to quit smoking with e-cigarettes that their use is not likely to disrupt their perceived sleep quality on average.

Sleep resilience is the ability to maintain effective emotional, cognitive, and physical functioning despite disruptions to sleep/circadian rhythms. While conceptually related to sleep health, no validated measure currently exists. This cross-sectional survey study aimed to validate a novel self-report measure of sleep resilience, the Sleep Resilience Questionnaire (SRQ), and examine its associations with demographic features, sleep disturbance, and sleep-related impairment. Our convenience sample included 455 adults (Mean age=45±17) in the United States who completed a demographic survey, PROMIS Sleep Disturbance (PROMIS-SD) and Sleep-Related Impairment (PROMIS-SRI), and retrospective and prospective SRQ forms (English version 1). Exploratory and confirmatory factor analyses (EFA and CFA) evaluated the SRQ's factor structure and internal consistency, and structural equation modeling examined associations with demographics, PROMIS-SD, and PROMIS-SRI. EFA and CFA supported a highly correlated two-factor retrospective SRQ structure and a unidimensional prospective SRQ structure with excellent fit and internal consistency (CFI & TLI>.99, RMSEA<.07, ω>.92). Lower sleep resilience was associated with greater sleep-related impairment (p<0.05) but not sleep disturbance. Younger age, men, higher education, greater number of dependents, and higher income were associated with lower sleep resilience in specific retrospective or prospective domains (p<0.05). Findings suggest sleep resilience is a meaningful dimension of sleep health, associated with demographic and sleep-related impairments, and the SRQ forms appear to validly measure it. Despite limitations of the cross-sectional design, the SRQ may be useful for future research aimed at identifying potential intervention targets to improve sleep-related impairments.

The glymphatic-meningeal lymphatic system plays a crucial role in brain waste clearance. Parasagittal dural (PSD) space contains meningeal lymphatic vessels. Calcification in the PSD space is an under-recognized sign. This study aims to explore the potential associations between PSD space calcification and demographic as well as sleep-related factors. In this retrospective study, consecutive patients who visited a sleep clinic between September 2015 and December 2023 were identified. All included individuals underwent a standard polysomnographic examination and a head and neck computed tomography (CT) scan. Demographic and anthropometric data, Epworth Sleepiness Scale scores, and polysomnographic measurements were examined as explanatory variables. CT scans were analyzed for the presence of calcifications in the PSD space. The calcifications were segmented with their volume calculated. Zero-inflated negative binomial regression was used to evaluate the association between calcification volume in the PSD space and the explanatory variables. A total of 72 patients (mean age, 41.14 ± 12.72 [standard deviation], 63 men) were included. Of the 72 patients, 17 patients (23.61 per cent) had PSD space calcification. Multivariate analysis revealed that body mass index (BMI) (p < .001), the duration of stage 3 non-rapid eye movement sleep (p < .01), and moderate-to-severe sleep apnea (p = .01) were independently associated with calcification volume in the PSD space. Higher BMI, reduced duration of stage 3 non-rapid eye movement sleep, and moderate-to-severe sleep apnea were independently associated with a larger volume of calcification in the PSD space, suggesting a potential link between these factors and impaired meningeal lymphatic function.

Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a loss of orexin-producing cells in the brain and involves autoimmune mechanisms, including the presence of autoreactive T cells. In this study, we performed genome-wide DNA methylation analysis using both CD4+/CD8+ T cells from 42 NT1 patients and 42 controls across discovery and replication cohorts. To identify methylation changes more robustly associated with the disease, we prioritized differentially methylated regions (DMRs) over single-site differentially methylated positions (DMPs). Furthermore, to validate and interpret DMP-level associations, we integrated genome-wide genotype and gene expression data obtained from the same individuals. As a result, the DMR analysis identified 15 reproducible DMRs in CD4+ T cells and 5 in CD8+ T cells, with most DMRs shared between the two cell types. Shared DMRs included regions associated with CCL5 (p= 2.1E-02) and CCR4 (p= 8.3E-03). Integrative analysis with genotype and gene expression data also showed that the DMP related to S100A4, which promotes lymphocyte migration through CCR5 and CXCR3 receptors, was associated with the disease in CD4+ T cells. Pathway analysis of genes identified through both the DMR and integrative analyses indicated enrichment in cell chemotaxis-related pathways, suggesting that aberrant chemokine-mediated cell migration plays a central role in NT1 pathogenesis. Further, NT1-associated methylation changes were predominantly hypomethylation events, significantly enriched in non-promoter, non-CpG island regions (p= 1.74E-102). We further observed that global hypomethylation levels were correlated with hypoSC, a mitotic index estimated from methylation data, highlighting increased T cell proliferation in NT1.

We aim to analyze the microbiota composition in Restless Legs Syndrome (RLS) patients and its relationship with the different RLS phenotypes. We recruited idiopathic RLS (RLS) and insomnia (INS) patients and healthy subjects (CTRL). Validated questionnaires (Pittsburg Sleep Quality Index, International Restless Legs Syndrome Study Group Rating Scale, Insomnia Severity Index, Beck Depression Inventory-II) were administered in the RLS and INS. Fecal microbiota was analyzed by 16S rRNA gene sequencing according to Illumina metagenomics standard procedure on MiSeq Platform. Dada2 pipeline was used to process sequencing data, while DESeq2 and Aldex2 tools were used to calculate differential abundance taxa, correcting for age, sex, body mass index, sequencing run, and presence of mood disorders. The sample included 37 RLS (28 females, mean age 64.78years), 31 INS (22 females, mean age 60.64years), and 33 CTRL (24 females, mean age 62.54years). Differential abundance analysis revealed a statistically significant decrease in the abundance of Lachnoclostridium and Flavonifractor genera in RLS compared to CTRL and INS, but not in the INS compared to CTRL. Lachnoclostridium abundance tended to decrease with long disease duration and a predominant motor phenotype. In the RLS group, several genera were identified as significantly associated with International Restless Legs Syndrome Study Group Rating Scale and Pittsburg Sleep Quality Index scores. Although only a few previous studies have reported the presence of small intestinal bacterial overgrowth in RLS, to the best of our knowledge this is the first study to highlight significant differences in the gut microbiota composition of RLS compared to both CTRL and INS, identifying a specific RLS metagenomic signature. Statement of Significance This is the first study to comprehensively characterize the gut microbiota in patients with Restless Legs Syndrome (RLS), identifying a distinct microbial signature compared to insomnia patients and healthy controls. We observed alterations alpha and beta diversity and specific changes in bacterial families and genera, some of which significantly correlated with RLS clinical features. In particular, Lachnoclostridium genus was significantly reduced in RLS and tended to be less abundant in patients with longer disease duration and without sensory symptoms. This genus is known to modulate systemic inflammation through the production of short-chain fatty acids, suggesting a potential link between gut dysbiosis, inflammation, and dopaminergic dysfunction. These findings support a role for gut microbiota alterations in RLS pathogenesis and open new avenues for microbiota-based diagnostic and therapeutic strategies.

Study objectives:Obstructive sleep apnea (OSA) is associated with maladaptive changes to glucose homeostasis. Chronic intermittent hypoxia (IH) modeling OSA in rodents causes similar patterns of dysglycemia. Time-restricted eating (TRE), limiting caloric intake to a fixed daily window, improves the metabolic profile in rodents and humans, though it is unknown whether TRE improves IH-induced dysglycemia in an obese OSA model.Methods:C57BL/6J mice were fed a high-fat diet for 4 weeks, and then divided into four groups: Half in intermittent air (IA) or IH, and half from each group fed either ad libitum or by TRE, restricting high-fat diet intake to 9 h/day during the dark phase; exposures continued for four additional weeks. Glucose tolerance tests were performed before and after exposures.Results:Fasting glucose was reduced in IH-TRE (−25.4 ± 5.6 mg/dL, p < .001) but not in other groups. Glucose tolerance test area under the curve was only increased in the IA-ad lib (3155 ± 924 mg*min/dL, p = .002) and IH-ad lib groups (5267 ± 1161 mg*min/dL, p < .001), but TRE prevented these increases. Insulin was elevated in IA-ad lib relative to other groups (p < .010 for all), implying insufficient insulin response to hyperglycemia in IH-ad lib. Serum proinsulin, and the proinsulin-to-insulin ratio, were elevated in IH-ad lib mice; this was normalized with TRE, along with favorable changes to pancreatic glucokinase, prohormone convertase 1/3, and miR-152–3p.Conclusions:In IH, TRE mitigates adverse hypoxic effects on glucose homeostasis, via improvements in pancreatic insulin secretion. Some beneficial glycemic effects of TRE are accentuated in IH. TRE may represent a novel therapeutic strategy in OSA.