Individualized approaches to pediatric chronic insomnia: Advancing precision medicine in sleep disorders

Sleep Medicine Reviews, Journal Year: 2024, Volume and Issue: 76, P. 101946 - 101946

Published: May 7, 2024

Language: Английский

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Synthesis and Characterization of a New Carbon-11 Labeled Positron Emission Tomography Radiotracer for Orexin 2 Receptors Neuroimaging

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 215 - 222

Published: Jan. 1, 2024

Purpose: Orexin receptors (OXRs) play a crucial role in modulating various physiological and neuropsychiatric functions within the central nervous system (CNS). Despite their significance, precise of OXRs brain remains elusive. Positron emission tomography (PET) imaging is instrumental unraveling CNS functions, development specific PET tracers for current research focus. Methods: The study investigated MDK-5220, an OX2R-selective agonist with promising binding properties (EC 50 on OX 2 R: 0.023 μM, Ki hOX 0.14 μM). Synthesized characterized as R probe, [ 11 C]MDK-5220 was evaluated its potential tracer. Biodistribution studies mice were conducted to assess selectivity, particular attention interaction P-glycoprotein (P-gp) blood-brain barrier. Results: exhibited attributes demonstrating robust selectivity biodistribution studies. However, observed P-gp impacted uptake. this limitation, presents itself candidate further development. Discussion: provides insights into functionality probe. highlights consideration future modifications enhance findings pave way innovative tracer propel ongoing systems, contributing deeper understanding CNS. Conclusion: emerges despite challenges related interaction. This lays foundation exploration probes targeting OXRs, opening avenues advancing our brain. Keywords: synthesis characterization, orexin-2 receptor, positron tomography, carbon-11 labeling, neuroimaging

Language: Английский

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The Triad of Sleep, Immunity, and Cancer: A Mediating Perspective

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1246 - 1246

Published: July 24, 2024

The triadic interplay between sleep, immunity, and cancer represents a growing area of biomedical research with significant clinical implications. This review synthesizes the current knowledge on how sleep influences immune function, system’s role in dynamics, direct connections patterns risk. After comprehensive overview interrelationships among these three domains, mechanisms function are described, detailing regulates system, effects duration quality responses, underlying molecular cellular mechanisms. Also, complex relationship immunity is explored, highlighting prevention progression, surveillance, tumor microenvironment, implications immunodeficiency modulation then presenting epidemiological evidence linking to risk, biological that influence development, disorders prognosis. mediating highlighted, proposing hypothesized pathways, summarizing from experimental studies, evaluating impact interventions outcomes. concludes by discussing future directions, emphasizing potential for sleep-based treatment, integration management oncology immunotherapy, outlining agenda. agenda includes understanding sleep–immunity–cancer interplay, conducting studies assessing treatment protocols, exploring microenvironment interactions, considering policy public health Through detailed examination interconnected this underscores critical importance modulating outcomes, advocating interdisciplinary strategies harness improved

Language: Английский

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Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models

Drug and Alcohol Dependence, Journal Year: 2024, Volume and Issue: 255, P. 111066 - 111066

Published: Jan. 9, 2024

Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) alcohol (AUD), a high-risk population.

Language: Английский

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Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder

Actas Españolas de Psiquiatría, Journal Year: 2024, Volume and Issue: 52(2), P. 172 - 182

Published: April 5, 2024

Insomnia disorder is a common condition that considered risk factor for multiple physical and mental disorders, contributing to reduced quality of life increased healthcare expenditures. Although cognitive behavioral therapy (CBT) typically recommended as the primary intervention, its accessibility hindered by limited resources, prompting prevalent use pharmacological interventions treatment in clinical settings. This study reviews benefits risks current treatments insomnia, with special reference orexinergic system novel therapeutic target treatment. The prescription GABAergic mechanism enhancers (benzodiazepine (BZD) "Z drugs") has shown efficacy short-term insomnia (less than 4 weeks), however, concerns arise regarding their long-term effectiveness, unfavorable tolerability safety profiles, including potential dependency. Drugs antihistamine properties, certain antidepressants antipsychotics, exhibit but have documented limitations, especially elderly. melatonin, available various formulations, lacks comprehensive data. Dual orexin receptor antagonists (DORAs) such daridorexant, lemborexant, suvorexant, represent approach inhibiting wakefulness rather enhancing sedation. As only DORA approved European Medicines Agency (EMA) Food Drug Administration (FDA), daridorexant demonstrated sustained over 12-month period, improving nocturnal sleep parameters daytime functionality, favorable profile.

Language: Английский

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Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite

Nutrients, Journal Year: 2023, Volume and Issue: 15(17), P. 3679 - 3679

Published: Aug. 22, 2023

Orexin plays a significant role in the modulation of REM sleep, as well regulation appetite and feeding. This review explores, first, current evidence on orexin sleep wakefulness highlights that should be considered essentially neurotransmitter inhibiting and, to much lesser extent, wake promoting agent. Subsequently, relationship between orexin, is examined detail, shedding light their interconnected nature both physiological conditions diseases (such narcolepsy, sleep-related eating disorder, idiopathic hypersomnia, night syndrome). Understanding intricate vital for unraveling complex mechanisms underlying sleep-wake patterns metabolic control. Further research this field encouraged order pave way novel therapeutic approaches disorders associated with dysregulation.

Language: Английский

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The Orexin System and Its Impact on the Autonomic Nervous and Cardiometabolic System in Post-Acute Sequelae of COVID-19

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 545 - 545

Published: Feb. 21, 2025

Orexins (OXs) are critical for regulating circadian rhythms, arousal, appetite, energy metabolism, and electrolyte balance, affecting both the autonomic nervous system (ANS) cardiovascular (CVS). Disruption of OX can result in symptoms similar to those observed post-acute sequelae COVID-19 (PASC). This review emphasizes adverse effects dysregulation on cardiometabolic functions patients with PASC. Additionally, we highlight potential anti-OX therapies provide neuroprotective, anti-inflammatory, immunoregulatory benefits, offering hope alleviating some debilitating associated

Language: Английский

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A randomised crossover trial of daridorexant for the treatment of chronic insomnia and nocturia

Journal of Sleep Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Summary This double‐blind, placebo‐controlled, two‐way crossover trial evaluated the efficacy and safety of daridorexant in patients with chronic insomnia comorbid nocturia. In total, 60 aged ≥55 years complaints for ≥3 months, Insomnia Severity Index (ISI) ≥13 voids/night ≥1 month were randomised (1:1) to 50 mg/placebo 4 weeks followed by after a 14–21‐day washout period. The primary endpoint was change from baseline Week (W) self‐reported total sleep time (sTST). Other endpoints included ISI score, depth quality (visual analogue scale scores), nocturnal voids (mean number, first) daytime functioning (Insomnia Daytime Symptoms Impacts Questionnaire score [IDSIQ]). At W4, significantly increased sTST versus placebo (least‐squares mean difference [LSMD] 20.9 min, 95% confidence interval [CI] 8.0–33.7; p = 0.002); significant improvements also seen at W1–3. Compared placebo, decreased ( < 0.001) both timepoints, W2 (LSMD −3.7, CI −5.1 −2.3) W4 −3.3, −4.7 −1.8) improved 0.05) (W1, 2, 3, 4), 3) IDSIQ 3). Daridorexant reduced number [95% CI]: W1–0.6 [−0.9 −0.3], 0.001; W4–0.3 [−0.7 +0.1], 0.090) median first void (difference W1: +31 0.0027; W4: +23 0.2026). No adverse events special interest (falls/urinary incontinence) reported during treatment. conclusion, nocturia, improves conditions favourable profile.

Language: Английский

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Orexin receptors: possible therapeutic targets for psychiatric disorders

Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Language: Английский

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A Systematic Review of the Effects of Repetitive Transcranial Magnetic Stimulation Combined With Pharmacological Intervention on Sleep Quality and Depressive Symptoms in Patients With Depression

Stress and Health, Journal Year: 2025, Volume and Issue: 41(2)

Published: April 1, 2025

ABSTRACT To systematically evaluate the intervention effect of repetitive transcranial magnetic stimulation (rTMS) combined with pharmacological interventions on sleep quality and depressive symptoms in patients depression, identify optimal parameters, explore potential clinical applications to facilitate individualised therapeutic strategies. Databases including Pubmed, Web Science, Cochrane Library, Embase, CNKI, Wanfang Medical Database, VIP database were searched up 31 December 2024, for randomized controlled trials (RCTs) assessing rTMS disorders depression. Data analysis was performed using Stata software. 17 RCTs involving 1667 included. Meta‐analysis revealed that significantly improved (SMD = −0.57, 95% CI: −1.02 −0.12, P < 0.05) reduced −0.73, −1.37 −0.10, 0.05). Subgroup analyses showed parameters improving high‐frequency targeting left dorsolateral prefrontal cortex, high intensity, low total pulse count (< 1200 pulses), session duration ≤ 20 min daily, 5–8 weeks. For symptoms, a daily treatment 21–30 more effective under similar parameter conditions. effectively improves alleviates showing dose‐dependent parameters. However, prolonged disease course or greater symptom severity, particularly those vascular other neurological comorbidities, alone may be insufficient. Integrating additional strategies tailoring personalised protocols necessary optimise outcomes. Future research should further synergistic orexin receptor antagonists (ORAs), offering novel, multimodal approach managing depression comorbid insomnia.

Language: Английский

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