Search Results (3,431)

The brain maintains homeostasis partially by scavenging waste products. Failure of this function is closely associated with the onset and pathogenesis of various brain diseases, such as Alzheimer’s disease, sleep disorder, and the delay of the reparative process after brain injuries. We recently demonstrated that brain pericytes (BPCs) are sources of lipocalin-type prostaglandin D synthase (L-PGDS), a waste scavenger, in the brain. Based on the above, chemical compounds which promote L-PGDS production could have potential against brain diseases, such as dementia, sleep disorders, and brain injuries. However, the specific chemical compounds that may enhance L-PGDS production in BPCs have not yet been identified. In this study, we explored 158 chemical compounds from FDA-approved drug libraries with these activities. qPCR analysis showed that mirtazapine (MTZ), a noradrenergic and specific serotonergic antidepressant, can increase L-PGDS expression in BPCs as well as in mouse- (m-BPCs) and human-derived BPCs (h-BPCs) in a dose-dependent manner. Since L-PGDS is a secretory protein, m-BPCs and h-BPCs were treated with various MTZ doses and L-PGDS levels in the culture supernatant were investigated. Western blot analysis showed that L-PGDS levels were significantly increased in a dose-dependent manner in both cell types, indicating that MTZ promoted L-PGDS secretion from m-BPCs and h-BPCs. Thus, MTZ may have the potential to be applied as drug repositioning for various brain diseases other than depression by activating L-PGDS production in BPCs, highlighting the importance of BPCs as the source to maintain brain homeostasis. Full article

Melatonin occupies a paradoxical position in contemporary sleep medicine: despite its physiological role as a regulator of circadian timing, it is frequently used and perceived as a nonspecific “natural” hypnotic. Although melatonin demonstrates modest benefits for sleep initiation and clearer efficacy in circadian rhythm sleep–wake disorders, its clinical use is often undermined by diagnostic imprecision, inappropriate dosing, mistimed administration, inconsistent formulations, and inadequate patient counseling. Circadian disorders can be misclassified as primary insomnia, leading to symptomatic treatment approaches that fail to address the underlying phase misalignment. At the same time, supraphysiological doses and reflexive bedtime administration have become normalized despite evidence that melatonin acts primarily as a chronobiotic whose effects depend more on timing than dose. Regulatory inconsistencies and substantial variability in over-the-counter preparations further complicate safe and reproducible use. These factors contribute to avoidable treatment failure, inaccurate labeling of nonresponse, and persistent misconceptions regarding melatonin’s mechanism of action. Therefore, melatonin should be approached as a pharmacological intervention requiring the same diagnostic rigor, individualized dosing, and longitudinal assessment expected of other sleep therapeutics, particularly when integrated with behavioral and circadian interventions. Full article

Background: Accurate assessment of neonatal sleep is critical for monitoring brain development and identifying potential neurological disorders, yet manual scoring of multi-channel EEG recordings is labor-intensive and prone to variability. Methods: To address this, we propose a lightweight temporal–spatial feature fusion network for automatic neonatal sleep staging. The model employs a dual-branch architecture to separately capture temporal dependencies and spatial correlations in EEG signals, which are then integrated through feature concatenation and a compact classifier to obtain comprehensive feature representations while maintaining low computational complexity. Results: The framework was evaluated on a clinical neonatal dataset (CHFD) for tasks including sleep–wake classification, quiet sleep detection, and three-stage sleep staging, achieving superior performance compared with several state-of-the-art methods. Additional evaluation on the MASS-S3 adult dataset demonstrate that the model retains competitive accuracy and F1-score, indicating strong generalization across populations. Conclusions: These results suggest that jointly modeling temporal and spatial features enables robust and efficient automatic sleep staging. The proposed approach offers a practical solution for clinical applications and edge deployment, providing reliable, multi-dimensional assessment of neonatal brain activity and laying the groundwork for future studies integrating larger datasets or multimodal physiological signals. Full article

Background: Sedentary behavior is a major modifiable risk factor for chronic metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Despite recommendations promoting regular physical activity (PA), adherence remains low. DIA/01 is a multidisciplinary study designed to promote healthy lifestyles for the prevention and management of T2DM, supporting healthcare systems. Methods: A total of 123 adults with T2DM diagnosed will be enrolled at the Diabetes Center of the University Hospital of Perugia throughout 2025. Inclusion criteria are age 25–80 years, ability to walk independently, being inactive, and BMI 18.5–40 kg/m². Exclusion criteria include severe cardiovascular, central nervous system, or musculoskeletal diseases contraindicating PA. Participants will be randomized into three groups: (1) standard care (SC); (2) SC plus theoretical PA counseling (TCPA); and (3) SC plus TCPA plus a 3-month supervised mixed exercise program. The assessment, conducted at baseline and at 6 and 12 months, includes total weekly PA (WPA) time, using IPAQ-SF and actigraphy. Moreover, glycated hemoglobin, sedentary time (ST), functional capacity, body composition, cardiometabolic risk factors, dietary adherence, perceived barriers and willingness to initiate PA, readiness to change, health-related quality of life, and sleep quality will be studied. This study is registered in the Clinical Trials Registry on 13 May 2026, with the identifier NCT07583355. Conclusions: Participants in groups (2) and (3) are expected to show greater improvements in WPA, reductions in ST, and favorable changes in metabolic and functional outcomes compared with SC. This approach may support long-term engagement in regular PA and contribute to improving the clinical management of T2DM. Full article

Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota–gut–brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, prebiotics, dietary indices, and botanicals, in alleviating insomnia, restoring circadian rhythms, and modulating neurochemical markers. Methods: In strict accordance with PRISMA 2020 guidelines, we searched PubMed, ScienceDirect, Scopus, and The Cochrane Library for English language studies published from inception to March 31, 2026. Eligibility was restricted to studies with rigorously controlled designs, specifically randomized controlled trials (RCTs) and controlled in vivo animal studies. Interventions had to target the gut microbiota, with primary outcomes measuring sleep quality (subjective or objective) or sleep-related neurochemical markers. We excluded uncontrolled, single-arm, or observational designs; in vitro studies; non-original research; and studies involving subjects with severe medical or psychiatric comorbidities (e.g., cancer, ADHD, severe psychiatric disorders) to prevent confounding variables, though mild-to-moderate anxiety and depression were permitted. Risk of bias was assessed using the Cochrane RoB 2.0 and SYRCLE tools. Due to significant methodological heterogeneity, a narrative synthesis stratified by intervention and population was conducted. This review was not registered in PROSPERO. Results: A total of 56 studies (33 humans, 23 animals) met the inclusion criteria. Taxonomic nomenclature was updated to reflect 2020 reclassifications (e.g., Lactiplantibacillus plantarum). In human trials, interventions significantly improved subjective sleep metrics (PSQI, ISI). Recent additions demonstrated the efficacy of the Dietary Index for Gut Microbiota (DI-GM) and the improvement in N3 sleep latency by yeast mannan. Furthermore, whole-food patterns (e.g., the MIND diet) and Traditional Chinese Medicine (TCM) decoctions successfully enriched beneficial taxa, such as Bacteroides coprophilus, and increased short-chain fatty acid (SCFA) production. Animal models demonstrated that “psychobiotic” strains (Bifidobacterium breve, Lacticaseibacillus paracasei), prebiotics (GOS/PDX), and TCM formulas effectively restored GABA/5-HT profiles, lowered morning cortisol, and facilitated REM rebound in PCPA-induced models, while also consolidating non-rapid eye movement (NREM) sleep and downregulating clock genes (Per1/Per2). Conclusions: Psychobiotics, prebiotics, and botanicals represent a highly viable non-pharmacological strategy for treating insomnia. However, current evidence is constrained by a heavy reliance on subjective human questionnaires, short follow-up durations limiting insight into long-term stability, and a substantial translational gap between mechanistic rodent models and human clinical outcomes. Full article

Background: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which causes numerous metabolic changes, leading to non-alcoholic fatty liver disease (NAFLD). Our study explored the suggested role of hypoxia-inducible factor 1-α (HIF-1α) in the pathophysiological mechanisms linking OSA with NAFLD. Methods: This case-control study was conducted at the Sleep Disorders Unit at Qena University Hospital from March 2022 to October 2023, including 64 subjects (48 OSA patients; in a secondary analysis, OSA patients were further stratified according to the presence or absence of NAFLD–16 controls) who were subjected to a polysomnography (PSG) for apnea hypopnea index (AHI) and transient elastography for controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM). Serum levels of HIF 1-α, fasting blood glucose, and fasting insulin were measured. Results: HIF-1α level showed the highest significant value was in the severe group (p = 0.001). Additionally, the severe group had the highest LSM compared to the other groups (p = 0.032). OSA patients with NAFLD, compared to OSA patients without NAFLD, showed significantly higher BMI (42.74 vs. 29.11 kg/m², p < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) mean score (3.92 vs. 1.21, p < 0.0001), HIF-1α level (6.01 vs. 2.14 ng/L, p = 0.045), and the LSM score (5.55 vs. 3.85 kPa, p < 0.001). HIF-1α showed significant positive correlations with AHI (r = 0.515, p < 0.001), waist circumference WC (r = 0.291, p = 0.045), HSI (r = 0.3, p = 0.038), and CAP score (r = 0.288, p = 0.047). Conclusions: Although serum HIF-1α levels were significantly higher in OSA patients with NAFLD and correlated with indices of hepatic steatosis, HIF-1α was not identified as an independent predictor of NAFLD after adjustment for metabolic confounders, suggesting a potential role of hypoxia-responsive pathways in pathophysiology of NAFLD in OSA. Full article

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients. Full article

Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care—including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care—and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management. Full article

Background and Objectives: It is well established that obstructive sleep apnea syndrome (OSAS) is associated with functional lung volumes. The aim of this study was to investigate the relationship between morphological lung volume and the severity of OSAS. Materials and Methods: Adult patients evaluated for sleep disorders between January 2020 and January 2024 were retrospectively reviewed. Patients with an AHI greater than 5, who underwent both spirometry and thoracic CT within a three-month interval, were included. Spirometric functional volume and morphological CT lung volume were assessed. Associations between OSAS severity and both functional and morphological lung volumes were analyzed. Results: A total of 195 patients were enrolled, of whom 166 had CT scans suitable for lung volume assessment. Among all patients, 20 (10.3%) were in the mild, 39 (20.0%) in the moderate, and 136 (69.7%) in the severe OSAS group. Ordinal regression analysis was performed to evaluate the factors influencing these categories. Age (p < 0.001) and BMI (p < 0.001) were positively correlated with disease severity, whereas female sex was associated with a lower risk of severe disease (p = 0.003). Conclusions: Functional and morphological lung volumes did not affect OSAS severity. Functional and morphological lung volumes were positively correlated with each other. Both morphological and functional lung volumes showed negative correlations with BMI. Full article

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of upper airway surgery is less well defined. Methods: In this retrospective study, 49 patients with polysomnography-confirmed OSA who underwent upper airway surgery were evaluated. Respiratory and metabolic parameters—including apnea–hypopnea index (AHI), fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR)—were assessed preoperatively and at 6 months postoperatively. Associations between changes in AHI (ΔAHI) and insulin resistance (ΔHOMA-IR) were analyzed using correlation and receiver operating characteristic (ROC) analyses. Results: Significant improvements were observed in both respiratory and metabolic parameters. AHI decreased from 46.6 ± 25.8 to 20.7 ± 14.1 events/h (p < 0.001). Fasting plasma glucose, insulin levels, and HOMA-IR were significantly reduced postoperatively (all p < 0.05), while HbA1c showed a downward trend. Reduction in AHI was moderately correlated with improvement in insulin resistance (r = 0.527, p < 0.001). ROC analysis demonstrated modest discriminative ability of ΔAHI for identifying normalization of insulin resistance (AUC = 0.62). Conclusions: Upper airway surgery was associated with significant improvements in insulin resistance and glycemic parameters in patients with OSA. The correlation between airway improvement and metabolic change supports a physiological link between upper airway obstruction and insulin sensitivity. These findings suggest that upper airway surgery may represent a clinically relevant adjunct within multimodal strategies for metabolic risk reduction, particularly in patients unable to tolerate CPAP therapy. Full article

Background: Obstructive sleep apnea syndrome (OSAS) is a prevalent sleep-related breathing disorder associated with significant systemic complications and reduced quality of life. Mandibular advancement devices (MADs) represent an established alternative therapy for patients who cannot tolerate continuous positive airway pressure (CPAP). However, concerns remain regarding their potential effects on temporomandibular disorders (TMD). Materials and Methods: This retrospective exploratory study analyzed clinical records of 26 patients (mean age 55.4 ± 5.8 years) with polysomnography-confirmed OSAS and baseline TMD-related symptoms treated with a custom-made monobloc MAD. Clinical parameters were evaluated at baseline (T0) and after approximately 6 months of therapy (T1). Outcomes included apnea–hypopnea index (AHI), Epworth Sleepiness Scale (ESS), Fonseca Anamnestic Index, and health-related quality of life assessed using the SF-36 questionnaire. Repeated measures ANOVA and linear regression analyses were performed. Results: After six months of MAD therapy, a significant reduction in AHI was observed (30 ± 13.76 vs. 10.87 ± 3.9; p < 0.00001). Daytime sleepiness significantly decreased (ESS: 9.31 ± 3.53 vs. 3.38 ± 1.77; p < 0.00001). TMD symptom severity also decreased significantly according to the Fonseca Index (33.85 ± 17.74 vs. 10.00 ± 8.94; p < 0.00001). Quality of life scores improved significantly (SF-36: 41.15 ± 9.52 vs. 65.38 ± 5.82; p < 0.00001). Linear regression analysis showed no significant association between changes in AHI and changes in TMD symptoms, ESS scores, or quality of life. Conclusions: Within the limitations of this retrospective study, MAD therapy was not associated with symptom aggravation of temporomandibular disorders in patients with pre-existing TMD symptoms. Significant improvements in respiratory parameters, daytime sleepiness, and quality of life were observed after six months of therapy. Full article

Objectives: We aimed to examine the association between bubble tea consumption and anxiety symptoms among adolescents in Eastern China and to explore the potential role of sleep disturbance in the observed association between bubble tea consumption and anxiety symptoms. Methods: This study utilized cross-sectional baseline data from the Zhejiang Childhood Behavior and Health Cohort. Bubble tea consumption frequency was categorized as 0, 1–2, and ≥3 days per week. Anxiety symptoms were assessed using the Generalized Anxiety Disorder—7 (GAD-7) scale, while sleep disturbance was measured through self-reported items. Associations between bubble tea consumption and anxiety symptoms were examined using multivariable logistic regression models, and dose–response relationships were evaluated with restricted cubic spline (RCS) models. Subgroup analyses stratified by age, sex, school type, residence, and body mass index (BMI) were conducted to assess the consistency of the associations. An exploratory mediation analysis with bootstrap confidence intervals was performed to evaluate the indirect association through sleep disturbance. Sensitivity analyses using a stricter definition of anxiety symptoms (GAD-7 ≥ 10) were conducted to assess robustness. Results: A total of 11,847 adolescents aged 12–18 years were included, of whom 32.03% met the GAD-7 threshold for any anxiety symptoms (GAD-7 ≥ 5, including mild symptoms). Compared with non-consumers, adolescents consuming bubble tea 1–2 days per week had higher odds of anxiety (OR = 1.12, 95% CI: 1.02–1.22), while those consuming bubble tea ≥3 days per week had substantially higher odds (OR = 1.53, 95% CI: 1.30–1.80). Each additional day of bubble tea consumption per week was associated with 10% higher odds of anxiety (OR = 1.10, 95% CI: 1.06–1.14). RCS analysis demonstrated a significant positive linear association between bubble tea consumption and anxiety (p for non-linearity > 0.05). Associations were consistent across age, sex, school type, residence, and BMI categories (all p for interaction > 0.05). Sensitivity analyses yielded similar results. Exploratory mediation analysis suggested that sleep disturbance may be statistically related to a portion of the observed association between bubble tea consumption and anxiety symptoms. Conclusions: Higher frequency of bubble tea consumption was associated with greater odds of anxiety symptoms among adolescents in a dose–response pattern. Sleep disturbance may statistically explain part of the association. These findings should be considered hypothesis-generating and require confirmation in prospective longitudinal studies. Full article

Obstructive sleep apnea (OSA) constitutes a chronic disorder characterized by recurrent upper airway collapse during sleep. This condition is prevalent among patients with cardiac rhythm disturbances and represents a potent independent risk factor for arrhythmia. Although most studies have concentrated on the association between OSA and atrial fibrillation (AF), numerous investigations have established connections with ventricular and supraventricular arrhythmias. Arrhythmogenesis in OSA represents a complex multifactorial phenomenon. Acute mechanisms involve induction of negative intrathoracic pressure during the effort to breathe, which triggers recurrent episodes of hypoxia, hypercapnia, alterations in carbon dioxide and acid–base equilibrium, as well as surges in sympathetic nervous system activity. Chronic intermittent hypoxia (CIH) and negative thoracic pressure (NTP) induce atrial stretch, chronic structural remodeling, and elevated vagal tone, thereby heightening susceptibility to bradycardic and conduction arrhythmias. Intermediate pathways through which OSA may precipitate arrhythmia encompass heightened systemic inflammation, oxidative stress, a prothrombotic state, and vascular dysfunction. Long-term OSA is linked with atrial enlargement and fibrosis, ventricular hypertrophy, hypertension, and coronary artery disease. These factors predispose to cardiac arrhythmias through the following mechanisms: shortening of the atrial effective refractory period, abnormal automaticity, promotion of slowed and heterogeneous conduction, enhancement of reentrant arrhythmia persistence, and prolongation of the QT interval. In this paper, we aim to present the pathophysiological mechanisms underpinning the association between obstructive sleep apnea and cardiac arrhythmias. Understanding the precise pathophysiological pathways by which obstructive sleep apnea contributes to arrhythmogenesis will enable targeted preventive stratification of patients at risk for cardiovascular events and promote the development of innovative therapies to attenuate OSA-induced arrhythmogenicity. Full article

Sleep and dietary behavior are deeply conserved biological processes that co-evolved under ecological pressures shaping human anatomy, metabolism, immunity, cognition, and life history strategies. Major transitions in human dietary ecology, including plant-dominant hominin foraging, increased meat consumption, control of fire and cooking, agricultural domestication, industrialization, and postindustrial globalization, restructured nutrient intake, pathogen exposure, microbial ecology, metabolic demands, and temporal organization of behavior. Emerging evidence from evolutionary genomics, chronobiology, neuroendocrinology, and microbiome science indicates that sleep–feeding interactions represent a conserved adaptive regulatory module optimized for fluctuating energy availability and strong photoperiodic entrainment. Modern environments characterized by widespread availability of highly palatable, energy-dense foods rich in refined carbohydrates, added sugars, and multiple industrial additives, together with artificial light at night, continuous caloric access, sedentary behavior, and psychosocial stress produce a profound evolutionary mismatch destabilizing circadian–metabolic homeostasis. This mismatch is characterized by circadian disruption, temporal misalignment of feeding and sleep behaviors, and, in many populations, insufficient sleep duration. Within this conceptual landscape, the emerging framework of “evolutionary chrononutrition” proposes that metabolic health and sleep integrity depend not only on what humans eat, but critically on when food is consumed in relation to endogenous circadian architecture shaped across deep evolutionary time. This review synthesizes anthropological, physiological, and molecular evidence to develop an integrative evolutionary framework linking sleep and diet to contemporary cardiometabolic, neurodegenerative, inflammatory, and psychiatric disorders, with particular emphasis on how each major dietary transition plausibly altered sleep duration, architecture, circadian timing, neuroendocrine regulation, and the temporal alignment between feeding behavior and biological rhythms. Full article