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PeerJ 2024The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces...
The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF- and IL-1) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1 expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF- expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF- expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF- and IL-1), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1), pre-frontal cortex (IL-1), and hypothalamus (IL-1). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.
Topics: Animals; Male; Metyrapone; Sleep Deprivation; Mice, Inbred C57BL; Mice; Mifepristone; Glucocorticoids; Interleukin-1beta; Inflammation; Tumor Necrosis Factor-alpha; Corticosterone; Hypothalamo-Hypophyseal System; Brain; Receptors, Glucocorticoid
PubMed: 38952964
DOI: 10.7717/peerj.17539 -
Journal of Patient-reported Outcomes Jun 2024The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful... (Randomized Controlled Trial)
Randomized Controlled Trial
Re-examining the factor structure of the Insomnia Severity Index (ISI) and defining the meaningful within-individual change (MWIC) for subjects with insomnia disorder in two phase III clinical trials of the efficacy of lemborexant.
BACKGROUND
The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings.
METHODS
We endeavored to improve upon previous validation of ISI by examining structural components of confirmatory factor analysis (CFA) models using two large, placebo-controlled clinical trials of lemborexant for insomnia. Using the best-fitting two-factor solution, we evaluated anchor-based, distribution-based and receiver operating characteristic (ROC) curve methods to derive an estimate of the MWIC.
RESULTS
The model structure for the 7-item scale proposed in other research did not fit the observed data from our two lemborexant clinical trials (N = 1956) as well as a two-factor solution based on 6 items did. Using triangulation of anchor-based, distribution-based, and ROC methods, we determined that a 5-point reduction using 6 items best represented a clinically meaningful improvement in individuals with insomnia in our patient sample.
CONCLUSIONS
A 6-item two-factor scale had better psychometric properties than the 7-item scale in this patient sample. On the 6-item scale, a reduction of 5 points in the ISI total score represented the MWIC. Generalizability of the proposed MWIC may be limited to patient populations with similar demographic and clinical characteristics.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Male; Female; Severity of Illness Index; Middle Aged; Psychometrics; Adult; Factor Analysis, Statistical; Treatment Outcome; ROC Curve; Pyridines; Pyrimidines
PubMed: 38951287
DOI: 10.1186/s41687-024-00744-6 -
Zhonghua Yi Xue Za Zhi Jul 2024Insomnia disorder is the most common sleep disorder. It not only increases the risk of multiple somatic and mental disorders, but also carries a heavy social health...
Insomnia disorder is the most common sleep disorder. It not only increases the risk of multiple somatic and mental disorders, but also carries a heavy social health economic burden. Currently, there is a lack of diagnosis and treatment standards for insomnia disorder in primary medical institutions at home and abroad. To this end, the Chinese Sleep Research Society organized domestic sleep medical experts in sleep medicine to develop this consensus based on the latest research on insomnia disorder. The current consensus elaborates on the pathophysiological mechanism, epidemiology, diagnosis, screening assessment, prevention and control measures and basic management, and has established a total of 15 recommendations. These recommendations aim to provide comprehensive and standardized references and guidelines for the diagnosis and treatment of insomnia disorder.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Consensus; China
PubMed: 38951102
DOI: 10.3760/cma.j.cn112137-20240318-00608 -
The Journal of Nervous and Mental... Jul 2024Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic...
Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness resulting from loss-of-function genetic variants in the WFS1 gene. Individuals with WS1 manifest a spectrum of neuropsychiatric disorders. Here, we report a pediatric case of WS1, which stemmed from a novel biallelic WFS1 loss-of-function genetic variant. The individual initially presented with obsessive-compulsive disorder, which was successfully managed by fluvoxamine. After 2 months, the child manifested excessive daytime sleepiness. Clinical evaluation and sleep recordings revealed a diagnosis of narcolepsy type 2. Excessive daytime sleepiness was improved with methylphenidate. To the best of our knowledge, this is the first report of narcolepsy in WS1, which possibly arose during a progressive neurodegenerative process. We emphasize the need for in-depth screening for neuropsychiatric phenotypes and sleep-related disorders in WS1, for clinical management, which significantly improves the quality of life.
Topics: Humans; Female; Wolfram Syndrome; Narcolepsy; Obsessive-Compulsive Disorder; Child; Membrane Proteins
PubMed: 38949661
DOI: 10.1097/NMD.0000000000001784 -
Annals of the American Thoracic Society Jul 2024
Topics: Humans; Sleep Apnea, Obstructive; Machine Learning; Precision Medicine; Continuous Positive Airway Pressure; Male; Middle Aged; Female
PubMed: 38949604
DOI: 10.1513/AnnalsATS.202403-308ED -
Frontiers in Endocrinology 2024Analyzing bacterial microbiomes consistently using next-generation sequencing (NGS) is challenging due to the diversity of synthetic platforms for 16S rRNA genes and... (Comparative Study)
Comparative Study Observational Study
Comparative analysis of gut microbiota in children with obstructive sleep apnea: assessing the efficacy of 16S rRNA gene sequencing in metabolic function prediction based on weight status.
BACKGROUND
Analyzing bacterial microbiomes consistently using next-generation sequencing (NGS) is challenging due to the diversity of synthetic platforms for 16S rRNA genes and their analytical pipelines. This study compares the efficacy of full-length (V1-V9 hypervariable regions) and partial-length (V3-V4 hypervariable regions) sequencing of synthetic 16S rRNA genes from human gut microbiomes, with a focus on childhood obesity.
METHODS
In this observational and comparative study, we explored the differences between these two sequencing methods in taxonomic categorization and weight status prediction among twelve children with obstructive sleep apnea.
RESULTS
The full-length NGS method by Pacbio identified 118 genera and 248 species in the V1-V9 regions, all with a 0% unclassified rate. In contrast, the partial-length NGS method by Illumina detected 142 genera (with a 39% unclassified rate) and 6 species (with a 99% unclassified rate) in the V3-V4 regions. These approaches showed marked differences in gut microbiome composition and functional predictions. The full-length method distinguished between obese and non-obese children using the / ratio, a known obesity marker ( = 0.046), whereas the partial-length method was less conclusive ( = 0.075). Additionally, out of 73 metabolic pathways identified through full-length sequencing, 35 (48%) were associated with level 1 metabolism, compared to 28 of 61 pathways (46%) identified through the partial-length method. The full-length NGS also highlighted complex associations between body mass index z-score, three bacterial species (, , and ATCC 15912), and 17 metabolic pathways. Both sequencing techniques revealed relationships between gut microbiota composition and OSA-related parameters, with full-length sequencing offering more comprehensive insights into associated metabolic pathways than the V3-V4 technique.
CONCLUSION
These findings highlight disparities in NGS-based assessments, emphasizing the value of full-length NGS with amplicon sequence variant analysis for clinical gut microbiome research. They underscore the importance of considering methodological differences in future meta-analyses.
Topics: Humans; Gastrointestinal Microbiome; Child; Male; RNA, Ribosomal, 16S; Female; Sleep Apnea, Obstructive; Pediatric Obesity; High-Throughput Nucleotide Sequencing; Child, Preschool; Body Weight; Adolescent
PubMed: 38948515
DOI: 10.3389/fendo.2024.1344152 -
Theranostics 2024Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the...
Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.
Topics: Animals; Female; Primary Ovarian Insufficiency; Gastrointestinal Microbiome; Mice; Dysbiosis; Metabolomics; Sleep Deprivation; Ovarian Follicle; Oocytes; Fecal Microbiota Transplantation; Disease Models, Animal; Apoptosis
PubMed: 38948060
DOI: 10.7150/thno.95197 -
Progress in Orthodontics Jul 2024The American Association of Orthodontists white paper on obstructive sleep apnea and orthodontics remains the most authoritative statement on the topic. This was... (Review)
Review
BACKGROUND
The American Association of Orthodontists white paper on obstructive sleep apnea and orthodontics remains the most authoritative statement on the topic. This was produced in 2019 due to increasing orthodontic interest in obstructive sleep apnea (OSA) and the lack of formal guidelines for orthodontists. Since the white paper's release, advocacy for contrarian ideas and practices remain. Orthodontists are sometimes acting as primary care providers for OSA. Procedures appropriate only for screening are sometimes being used for diagnosis. The side effects of effective treatments such as mandibular advancement devices need further consideration. Also, research has clarified the effectiveness and ineffectiveness of treatments such as palatal expansion.
RESULTS
Part of an orthodontist's role is screening for OSA. The correct action when this is suspected remains referral to the appropriate physician specialist for diagnosis and treatment or coordination of treatment. Orthodontists may participate in the treatment of patients with OSA as a member of a multi-disciplinary team. Effective orthodontic treatments may include orthognathic surgery with maxillomandibular advancement and mandibular advancement devices. The negative effects of the latter make this a choice of last resort. Current research indicates that OSA alone is not sufficient indication for palatal expansion.
CONCLUSIONS
Orthodontists should appropriately screen for obstructive sleep apnea. This may be done as part of our health histories, our clinical examination, and review of radiographs taken for purposes other than the diagnosis and screening for OSA. Orthodontic treatment for OSA can be helpful and effective. However, this may be done only after referral to the appropriate physician specialist, as part of a multi-disciplinary team, with consideration of the likely effectiveness of treatment, and after all likely and potential negative consequences have been considered and thoroughly discussed with the patient.
Topics: Sleep Apnea, Obstructive; Humans; Orthodontists; Mandibular Advancement; Palatal Expansion Technique; Professional Role; Orthodontics; Orthodontics, Corrective; Referral and Consultation
PubMed: 38945976
DOI: 10.1186/s40510-024-00524-4 -
Brain and Behavior Jul 2024Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances...
Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.
INTRODUCTION
Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.
METHODS
Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods.
RESULTS
The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor.
CONCLUSION
Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.
Topics: Animals; Isoflurane; Female; Cognitive Dysfunction; Pregnancy; Sleep Deprivation; Mice; Hippocampus; Prenatal Exposure Delayed Effects; Neuroinflammatory Diseases; Anesthetics, Inhalation; Synapses; Male; Mice, Inbred C57BL; Maternal Deprivation; Brain-Derived Neurotrophic Factor
PubMed: 38945806
DOI: 10.1002/brb3.3610 -
Physical Medicine and Rehabilitation... Aug 2024Traumatic brain injury (TBI) is a complex condition associated with a range of persistent symptoms including headaches, cognitive dysfunction, mental fatigue, insomnia,... (Review)
Review
Complementary and Integrative Medicine in Treating Headaches, Cognitive Dysfunction, Mental Fatigue, Insomnia, and Mood Disorders Following Traumatic Brain Injury: A Comprehensive Review.
Traumatic brain injury (TBI) is a complex condition associated with a range of persistent symptoms including headaches, cognitive dysfunction, mental fatigue, insomnia, and mood disorders. Conventional treatments for TBI-related symptoms can be insufficient, leading to interest in complementary and integrative medicine (CIM) approaches. This comprehensive article examines the existing literature on CIM modalities, including mind-body interventions, acupuncture/acupressure, herbal remedies, nutritional supplements, biofeedback, yoga, and tai chi in the context of managing secondary complications following TBI. The article highlights potential benefits and limitations of CIM modalities, while acknowledging the need for further research to better establish efficacy and safety in this specific population.
Topics: Humans; Brain Injuries, Traumatic; Mood Disorders; Complementary Therapies; Sleep Initiation and Maintenance Disorders; Integrative Medicine; Headache; Cognitive Dysfunction; Mental Fatigue
PubMed: 38945657
DOI: 10.1016/j.pmr.2024.02.013