Search Results (282)

The circadian clock, located in the mammalian hypothalamus, regulates biological rhythms with a period of approximately 24 h, influencing nearly all body functions. Its timing is synchronised daily by external cues, primarily light, which align internal rhythms with the environmental cycle. Through this entrainment, the circadian system orchestrates physiological processes such as the sleep–wake cycle, feeding behaviour, gene expression and body temperature regulation. Melatonin, secreted by the pineal gland, also plays a key role as a synchroniser by facilitating sleep onset. Changes in environmental time cues, such as those experienced by shift workers, can disrupt the body’s natural 24-h rhythms. This situation can lead to fatigue, significantly impacting accident rates and productivity, and, in the long term, to an increased risk of various health conditions. A Phase Response Curve (PRC) illustrates how the clock’s phase is affected by stimuli administered at different points in the circadian cycle. In particular, both light and melatonin can induce phase shifts, but the direction and magnitude of this shift depend on the timing of administration. Understanding the PRC enables the design of interventions to realign circadian rhythms and improve adaptation to shift work. This review explores the physiological and clinical effects of circadian disruption in shift workers and discusses strategies to mitigate its impact. Full article

Objective: To explore the association of glucocorticoid (GC) exposure with objectively assessed sleep architecture in patients with rheumatoid arthritis (RA). Methods: A single-center exploratory pilot study involving 20 consecutive patients with RA (9 GC users and 11 non-users; mean age 64.9 years) was conducted. Using single-channel electroencephalography (EEG) and accelerometry, objective sleep architecture and autonomic balance were evaluated. Sleep parameters included wake after sleep onset (WASO), sleep stages, and delta EEG power during the first sleep cycle, while heart rate variability, expressed as low frequency/high frequency (LF/HF) ratio, was used as an index of autonomic balance. RA disease activity was evaluated using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Associations between clinical variables and objective sleep parameters were evaluated using Spearman rank correlation analysis. Results: Disease activity, assessed by DAS28-CRP, did not differ significantly between GC users and non-users. Compared with non-users, GC users had longer WASO (p = 0.011), shorter non-rapid eye movement (NREM) stage N3 duration (p = 0.010), and lower delta power (p = 0.014) than non-users. A higher nighttime-to-daytime LF/HF ratio was also observed in GC users, although this difference did not reach statistical significance. Total sleep time, sleep latency, and sleep efficiency were comparable between the groups. WASO was positively correlated with age, GC use, and GC dose, whereas NREM stage N3 duration and delta power were negatively correlated with GC exposure. No significant associations were observed between age or sex and objective measures of deep sleep. Conclusions: Among patients with RA, GC exposure was associated with poorer sleep continuity and reduced deep sleep despite comparable disease activity. Given the small sample size of this exploratory single-center study, these findings should be interpreted cautiously. Larger longitudinal studies using objective sleep measures are warranted to confirm these associations. Full article

Excessive mind wandering is increasingly recognized as a clinically relevant cognitive feature of adult attention-deficit/hyperactivity disorder (ADHD), yet its relationship with sleep-related characteristics remains insufficiently understood. This cross-sectional study with a control group examined associations between sleep-related characteristics and excessive mind wandering in 316 adults with clinically confirmed ADHD and 121 screened controls. Participants completed measures of ADHD symptoms, mind wandering, anxiety–depressive symptoms, and self-reported sleep-related characteristics adapted from Pittsburgh Sleep Quality Index items; mid-sleep time was calculated from reported sleep onset and final awakening. Group comparisons, correlation analyses, and multiple regression analyses were conducted. Adults with ADHD showed higher mind wandering, greater ADHD symptom severity, anxiety–depressive symptom burden, poorer subjective sleep quality, and later mid-sleep time than controls, whereas sleep duration did not differ between groups. Mind wandering was associated with ADHD symptom severity, anxiety–depressive symptoms, later mid-sleep time, and poorer subjective sleep quality. In regression analysis, ADHD diagnosis was the strongest independent correlate of mind wandering. Anxiety–depressive symptom burden, poorer subjective sleep quality, and later mid-sleep time, but not sleep duration, also remained independently associated with higher mind wandering. Findings suggest that sleep timing and subjective sleep quality may be clinically relevant to excessive mind wandering in adults with ADHD. Full article

Background: Cardiometabolic risk is shaped not only by the amount of food intake and physical activity but also by their timing and regularity across the 24 h cycle. We propose rhythm coherence as a hypothesis-generating framework describing the temporal stability and alignment of eating, physical activity, and sleep. Its vascular and glycemic relevance has not yet been prospectively validated. Methods: This semi-structured narrative review was supported by a transparent, staged evidence-identification process using PubMed, Scopus, and Web of Science Core Collection. Main searches used a 2020–2026 window, with a broader 2018–2026 window for targeted athlete-focused searches. After cross-database deduplication, 1081 unique records entered broad screening; 694 underwent strict screening, yielding 257 core candidate records. A targeted athlete-focused search contributed 46 additional records, producing a 303-record candidate evidence pool for topic mapping. From this pool, 131 high-priority records underwent full-text narrative synthesis, and 92 sources were ultimately cited directly in the manuscript. These counts represent successive review stages rather than a PRISMA-defined systematic-review inclusion set. Results: Earlier or more regular eating patterns, postprandial physical activity, and stable sleep–wake schedules were associated with more favorable cardiometabolic profiles in selected studies. However, the evidence was heterogeneous and included mechanistic studies, observational analyses, and intervention trials. These findings support further investigation but do not establish an effect of integrated eating–activity–sleep coherence. Numerical effects reported for individual interventions should not be attributed to the proposed integrated framework or to the Rhythm Coherence Index (RCI). Conclusions: Coordinated assessment of eating, activity, and sleep timing may offer a useful research direction. The RCI is an author-proposed candidate composite, not an existing validated instrument or clinical decision rule. Its formula, component weights, missing-data procedures, thresholds, reliability, responsiveness, predictive value, and external validity require prospective evaluation before clinical application can be considered. Full article

Aging disrupts sleep, but how these changes are structured across circadian time, vigilance states, and sex remains poorly understood, because most prior studies used single-sex cohorts and few days of recordings. We continuously recorded 14 days of EEG/EMG in 24 C57BL/6J mice using a balanced 2 × 2 design (young vs. old; male vs. female; n = 6/group). A comprehensive multiscale analysis of the extended dataset enabled detailed reconstruction of 24 h sleep–wake architecture, better characterization of natural day-to-day variability including across multiple estrous cycles, and detection of rare bouts and transition events. Across seven levels of analysis, from circadian profiles to EEG spectral parameterization, the strongest aging effect was a dark-phase-specific 17–18% loss of theta-dominant active wake (TDW) in both sexes, with reciprocal increases in quiet wake (nTDW) and NREM sleep. We also identified a recurring N-shaped structural motif at the dark-to-light transition, where age-related and several sex-associated differences were most apparent. Broadly, old mice exhibited (i) shorter TDW bouts; (ii) a shift in NREM exit kinetics toward wakefulness; (iii) more brief and poorly consolidated “out-block” NREM episodes; and (iv) a slowing of waking theta and higher low-frequency TDW power. Variance decomposition indicated that statistical power depends more on sample size than on recording length. Together, aging reflects a coordinated, circadian-phase-specific reorganization of sleep–wake architecture. Sex-related and interaction findings should be interpreted as hypothesis-generating pending larger cohorts. Full article

Epilepsy is increasingly conceptualized as a disorder of dynamic network instability rather than a static imbalance between excitation and inhibition. However, substantial variability in seizure occurrence, clinical expression, and treatment response remains insufficiently explained by existing models. This narrative review examines how neurotransmitter systems contribute to seizure dynamics within a state-dependent framework, in which factors such as sleep–wake cycles, stress, inflammation, and metabolic conditions modulate network excitability. The review identified four key findings: neurotransmitter function in epilepsy is state-dependent rather than fixed; multiple physiological state modifiers shape seizure susceptibility; seizure termination is an active state-sensitive process; and biomarker performance depends on the prevailing brain state. Evidence from experimental and clinical studies indicates that neurotransmitter function is context-sensitive and interacts with molecular pathways, including ion channel function, synaptic plasticity, and neuromodulatory signaling. These interactions influence key stages of seizure dynamics, including initiation, propagation, and termination, and may differ across etiological categories of epilepsy. This perspective also helps explain the limited performance of static biomarkers, as they do not capture temporal variability in network states. Instead, state-sensitive markers and context-aware interpretations of electrophysiological and clinical data may provide more informative insights. Overall, integrating neurotransmitter mechanisms with dynamic brain states offers a more precise perspective on seizure variability and may support the development of individualized, state-aware approaches to epilepsy management. Full article

Background: We previously demonstrated recapitulation of the relative hypogonadotropic hypogonadism of obesity, the Reprometabolic Syndrome (RMS), in women of normal BMI with a one-month high-fat, eucaloric diet (HFD). Objective: Assess effects of HFD on sleep, body composition and lifestyle and metabolic secondary outcomes and correlate insulin sensitivity changes with the RMS. Methods: A total of 18 normally cycling women aged 18–38 with BMI 18–24 kg/m² were enrolled for a four-month study including a eucaloric HFD (48% calories from fat) for one menstrual cycle. Activity, sleep, body composition, and the lipidome were measured in all participants. Fecal microbiome was analyzed in the last nine participants, and insulin sensitivity by two-stage hyperinsulinemic euglycemic clamp was measured before and after HFD in 15 participants. Results: Relative to the pre-diet period, BMI, activity and sleep measures did not change, except for waking after sleep onset (WASO), which appeared to decrease during and post HFD. DXA revealed statistically significant decreases in total percent fat, total fat mass, visceral fat volume, and trunk fat volume. Whole-body insulin sensitivity decreased with the HFD while adipocyte insulin sensitivity was unaffected. Insulin sensitivity changes did not correlate with change in gonadotropins or response to gonadotropin releasing hormone (GnRH). Multiple significant changes in plasma lipids were observed, including increased ceramides and glucosylceramides. Microbiome analysis revealed increased microbial diversity. Conclusions: A one-month eucaloric HFD that induced RMS in normal-weight, reproductive-aged women also induced whole-body insulin resistance (IR) and multiple lipidomics changes potentially associated with IR. These changes in IR occurred despite overall stable activity, BMI and sleep, but did not correlate with the HPO axis defects. The unexpected decrease in body fat and increase in microbial diversity may be related to specific dietary elements of the HFD. Full article

Background: Gastroesophageal reflux disease (GERD) is a common digestive disorder with a substantial impact on quality of life. Emerging evidence suggests that dietary patterns and lifestyle behaviors are associated with the occurrence and severity of GERD symptoms; however, integrated data from Romania remain limited. Objective: The aim of this study was to evaluate associations between pro- and anti-inflammatory dietary patterns, lifestyle-related behavioral factors, and the presence and severity of gastroesophageal reflux symptoms in an adult Romanian population. Methods: A national cross-sectional observational study was conducted using a self-administered online questionnaire. All participants included in the study reported a prior diagnosis of gastroesophageal reflux disease (GERD), and participant classification was based exclusively on current symptomatology assessed using the GERD-Q score. Therefore, comparisons were not performed between patients and a healthy population, but rather between individuals at different stages of clinical expression of the same condition, characterized by a fluctuating course. The instrument included standardized GERD-Q items for symptom assessment, together with questions regarding dietary intake and lifestyle behaviors. Pro-inflammatory (PRO), anti-inflammatory (ANTI), and combined (PRO–ANTI) dietary scores were established. Statistical analyses included comparative and correlational tests as well as multivariable logistic regression models. Results: Among the 340 participants included in the study, 72.4% reported symptoms consistent with GERD according to the GERD-Q score. A higher pro-inflammatory dietary score was significantly associated with GERD, with participants in the highest PRO category showing more than a fourfold higher likelihood of GERD in multivariable analyses. Consumption of spicy foods and carbonated beverages was associated with an increased risk of GERD in univariate analyses; however, these associations did not remain significant in multivariable models. Late meals (defined as consumption of one’s last meal of the day less than two hours before bedtime) were independently associated with GERD. Combined analyses indicated a higher risk among participants who reported eating late meals, particularly when combined with large evening meals. Most foods considered protective, along with classical lifestyle factors (smoking, alcohol consumption, and sleeping position), were not independently associated with GERD. Conclusions: These findings suggest that overall dietary patterns with pro-inflammatory potential and meal timing in relation to the sleep–wake cycle may be more consistently associated with GERD symptoms in this sample than isolated food items or traditional lifestyle risk factors. Nutritional and behavioral interventions focused on improving overall dietary patterns and avoiding late meals may represent potential strategies for GERD management. Full article

Sleep is a cardinal biological process that backstops central nervous system function, which also plays a crucial role in regulating systemic homeostasis, including immune activities. Cytokines, particularly interleukin-1β and tumor necrosis factor-α, act as mediators bridging sleep and inflammation, also influencing both sleep architecture and sleep–wake cycle. Sleep deprivation and sleep disorders such as insomnia, narcolepsy, hypersomnia, or obstructive sleep apnoea may disrupt cytokine production, alter their circadian rhythm of release, and shift secretion peaks from night to day. These changes contribute to daytime fatigue, impaired cognitive and physical performance, increased susceptibility to infections and/or systemic inflammation. Molecular studies indicate that insufficient sleep primes immune cells to enhance pro-inflammatory responses, creating a feedback loop with neuroendocrine pathways that further exacerbates sleep patterns and inflammatory dysregulation. Understanding the bidirectional relationship between sleep and cytokines may highlight the role of sleep as an active component of immunity regulation and underscore the potential usefulness of multilevel interventions that include complementary and integrative health approaches restoring sleep, normalizing cytokine rhythms and mitigating inflammation. Full article

Insomnia is one of the most common sleep disorders. Traditionally, its pathophysiology has been interpreted mainly from the perspective of the central nervous system (CNS). However, accumulating evidence suggests that the microbiota–gut–brain axis (MGBA), a bidirectional communication network linking the gut and the CNS, may play an important role in the development, maintenance, and treatment of insomnia. This review summarizes the major signaling pathways of the MGBA and discusses its potential mechanisms in insomnia. Current evidence indicates that gut microbiota and their metabolites may influence sleep–wake homeostasis through neural, immune, endocrine, and circadian pathways. At the same time, insomnia-related stress responses, immune imbalance, and lifestyle disturbances may in turn affect the gut microbiota, thereby forming a bidirectional regulatory network. Animal and clinical studies further support a close association between gut microbial dysbiosis and insomnia. In addition, this review systematically summarizes factors that may affect the MGBA, including diet, lifestyle, psychosocial stress, medications, and medical exposures. On this basis, MGBA-targeted interventions, such as dietary modification, prebiotics and probiotics, lifestyle interventions, fecal microbiota transplantation, and natural medicines, may provide promising new strategies for the prevention and treatment of insomnia. Nevertheless, the current evidence still relies largely on animal studies and cross-sectional research, and further longitudinal studies and high-quality interventional trials are needed to clarify causality, long-term efficacy, and standardized therapeutic approaches. Full article

Background: Sensorimotor differences have frequently been reported in children with developmental dyslexia, but are often considered secondary or comorbid to phonological deficits. Within an embodied cognition perspective, reading acquisition emerges from dynamic interactions between bodily regulation, multisensory integration, and learning-related neural plasticity. Proprioception contributes to spatial orientation, motor coordination, and perceptual stabilization, while sleep-dependent processes play a critical role in the consolidation and automatization of cognitive and motor skills. Objectives: Building on early clinical observations, including the hypothesis proposed by Martins da Cunha, this review explores whether variations in proprioceptive processing and sensorimotor regulation may influence multisensory stability and the conditions under which reading skills develop in some individuals with dyslexia. Methods: This narrative synthesis integrates clinical observations and experimental paradigms examining proprioceptive function in children with dyslexia, including studies conducted in our laboratory over the past two decades. These investigations address postural regulation under varying attentional demands, laboratory measures of proprioceptive acuity, visuospatial localization tasks, multisensory interactions, and exploratory observations concerning sleep–wake regulation. Results: Across studies, children with dyslexia often show differences in proprioceptive processing associated with variations in postural regulation, visuospatial stability, and multisensory tasks. Laboratory measurements suggest reduced proprioceptive acuity in some individuals, with moderate correlations observed between proprioceptive sensitivity and reading-related measures. Additional observations suggest that nocturnal physiological regulation—including respiratory dynamics and sleep architecture—may interact with daytime sensorimotor stability and attentional functioning. Conclusions: Taken together, these findings support the hypothesis that variations in sensorimotor regulation across the sleep–wake cycle may influence the stability of multisensory processing and attentional conditions relevant for reading acquisition. Within this perspective, proprioception is not proposed as an alternative explanation for dyslexia but as a complementary dimension that may contribute to the heterogeneity of dyslexic profiles. Further longitudinal and controlled studies are required to clarify the relationships between sensorimotor regulation, sleep-dependent plasticity, and learning processes. Full article

Canine cognitive dysfunction (CCD) is a common age-related neurodegenerative disorder in dogs that shares several pathological and clinical features with human Alzheimer’s disease (AD). In both species, β-amyloid (Aβ) accumulates within the brain parenchyma and cerebral vessel walls and is associated with synaptic loss, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, ultimately leading to progressive cognitive decline. Increasing evidence indicates that impairment of brain clearance mechanisms, particularly the glymphatic system, represents a central pathogenic mechanism in both CCD and AD. The glymphatic system is a glia-dependent perivascular network involved in the clearance of Aβ and other metabolic waste products from the brain. Its function declines with aging, vascular disease, and astrocytic alterations, including changes in aquaporin-4 distribution. Reduced glymphatic and periarterial drainage promotes the retention and aggregation of Aβ and tau proteins. Compared with AD, tau pathology in CCD is generally less extensive, supporting the interpretation of CCD as an Aβ-predominant condition and a partial pathological analog of Alzheimer’s disease. Clinically, CCD is characterized by a constellation of behavioral changes including, disorientation, altered social interactions, sleep–wake cycle disturbances, a loss of housetraining, changes in activity levels, and increased anxiety, commonly summarized by the DISHAA acronym. Overall, CCD represents a valuable spontaneous large-animal model for investigating neurodegenerative mechanisms and clearance-related therapeutic targets relevant to both veterinary and human medicine. Full article

Melatonin, an indoleamine crucial for regulating circadian rhythms, sleep–wake cycles, and immune–endocrine homeostasis, is present in biological fluids at extremely low concentrations, making its quantification analytically challenging. This narrative review provides a critical comparative assessment of current methodologies for melatonin determination across various biological matrices—plasma, urine, saliva, breast milk, and hair. The discussed techniques include immunoassays, colorimetric and spectrophotometric methods, chromatographic–mass spectrometric platforms (LC–MS/MS, UHPLC–MS/MS), and emerging biosensors. Each approach is evaluated regarding analytical sensitivity, specificity, reproducibility, cost, and clinical applicability. While immunoenzymatic and colorimetric techniques offer accessible, low-cost solutions for large-scale or preliminary studies, LC–MS/MS remains the benchmark for reference analysis, providing sub-picogram detection limits and multiplexing capability. However, its high cost, procedural complexity, and inter-laboratory variability limit routine implementation. New developments, including molecularly imprinted polymers, dispersive microextraction, and nanomaterial-based biosensors, suggest a shift toward hybrid, sustainable, and portable analytical platforms. By synthesizing recent methodological advances and identifying key limitations, this review aims to guide researchers and clinicians in selecting the most appropriate analytical approach for clinical, pharmacological, and circadian biomonitoring applications. Full article

Astrocytes critically regulate states of consciousness, yet their molecular profiles across wake, sleep, and general anesthesia remain unclear. This study conducted proteomic and phosphoproteomic analyses of rat cortical astrocytes across these states using sevoflurane. Data quality was validated using principal component analysis (PCA) and Pearson correlation coefficient (PCC). Proteomics showed state-specific signatures: sleep and anesthesia shared similar changes (downregulated structural proteins, upregulated membrane transport complexes) but diverged in molecular expression. Anesthesia specifically suggested potential activation of cellular differentiation/structural plasticity-related pathways but implied potential disruption of metabolism and molecular clearance processes compared to sleep. Phosphoproteomics revealed the unique phosphorylation changes during general anesthesia compared to wake and normal sleep: downregulated phosphorylation of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) at Ser188, suggesting the potential suppression of nuclear transcription and/or cell cycle activity, which may act as a potential molecular signature associated with the anesthetic state. Clustering analysis showed that sleep was associated with upregulated mRNA processing, while anesthesia indicated potential enhancement of synaptic signaling and suggested possible suppression of development-related programs. In summary, astrocytes undergo extensive molecular reprogramming during transitions of consciousness; while they share common features in morphological remodeling, sleep and anesthesia differ fundamentally in astrocytic molecular outcomes, offering new insights into astrocytic roles in unconsciousness. Full article

Purpose of Review—sleep disturbance is the main complaint associated with patients who suffer acute postoperative pain. Sleep disturbance may also increase the pain sensitivity and contribute to the development and maintenance of chronic pain. The pathophysiology of pain is complex; management of perioperative pain and preventing chronic pain are challenges in clinical. Use of opioids for pain management are still a therapeutic mainstay and generally safe when taken, in a short time, for severe postoperative pain relief. For long-term use tolerance may be developed, and for their euphoric property, addiction, overdose incidents, and even death may be the social problems. Therefore, the opioid-sparing multimodal analgesia (MMA) for pain management is recommended in current postoperative pain management. The successful MMA for pain management will enhance patient recovery after surgery with less chronic CPSP and long-term opioid use disorder (OUD). The present review discusses all currently used analgesics actions and interactions, and opioid-sparing or opioid-free analgesia in perioperative pain management. Acute pain following major trauma or surgery may originate from both nociceptive and neuropathic mechanisms. Approximately 10–50% of surgical patients develop chronic postoperative pain, which not only causes persistent discomfort but also leads to functional limitations and psychological distress. Growing evidence highlights a close and bidirectional relationship between sleep and pain: pain disrupts sleep architecture, while sleep deprivation intensifies pain sensitivity and impairs recovery. This reciprocal interaction forms a vicious cycle that poses challenges for effective pain management. Melatonin—a neurohormone secreted by the pineal gland—plays a crucial role in regulating circadian rhythm and sleep–wake cycles. Beyond its chronobiotic action, melatonin exhibits anti-nociceptive, anti-inflammatory, and opioid-sparing properties. Recent preclinical studies have demonstrated that exogenous melatonin can attenuate nociceptive responses to noxious stimuli and enhance morphine analgesia while attenuating morphine tolerance. Moreover, environmental light manipulation preserving the circadian rhythm has been shown to synergistically maintain melatonin secretion, improve sleep quality, and modulate neuroimmune responses involved in pain regulation. Together, these findings suggest that circadian alignment and melatonin supplementation may represent a promising integrative approach for improving both pain control and sleep health in perioperative and chronic pain conditions. Chronic pain patients frequently experience opioid tolerance during long-term therapy, resulting in diminished analgesic efficacy and a need for escalating doses. Our recent work revealed that constant light exposure suppresses endogenous melatonin, heightens pro-inflammatory cytokines (TNF-α, IL-1β), reduces IL-10, and accelerates morphine tolerance in a neuropathic pain model. In contrast, maintaining circadian light–dark cycles or supplementing melatonin preserves melatonin rhythm, reduces glial activation, and sustains morphine antinociception. Melatonin’s co-administration not only attenuates morphine tolerance but also enhances morphine efficacy through the modulation of inflammatory and glial pathways. These findings underscore melatonin’s multifaceted role as both a chronotherapeutic and neuroprotective agent, integrating circadian regulation with pain modulation. Clinically, the application of melatonin or circadian-aligned strategies could guide personalized pain and sleep management, offering safer and more effective multimodal analgesic protocols with reduced opioid dependence and improved quality of life. Full article