The association between the effective apnea-hypopnea index and blood pressure reduction efficacy following CPAP/oxygen treatment.

BACKGROUND: The effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. METHODS: A secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (▲AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. RESULTS: One hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had ▲AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015-1.058, p: 0.001) and ▲AHI ≥8/hour (OR 2.406, 95% CI 1.116-5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (ß: -2.564, SE: 1.167, p: 0.029) and positively related with troponin change (ß: 0.703, SE: 0.256, p: 0.007). CONCLUSION: The ▲AHI was an independent predictor of the blood pressure response to sleep apnea treatment. REGISTER NUMBER: NCT01086800.

A meta-analysis of the association between insomnia with objective short sleep duration and risk of hypertension.

The aim of this meta-analysis was to examine the association between insomnia with objective short sleep duration (ISSD) with prevalent and incident hypertension in cross-sectional and longitudinal studies, respectively. Data were collected from 6 cross-sectional studies with 5914 participants and 2 longitudinal studies with 1963 participants. Odds ratios (ORs) for prevalent and risk ratios (RRs) for incident hypertension were calculated through meta-analyses of adjusted data from individual studies. Compared to normal sleepers with objective normal sleep duration (NNSD), ISSD was significantly associated with higher pooled OR for prevalent hypertension (pooled OR = 2.67, 95%CI = 1.45-4.90) and pooled RR for incident hypertension (pooled RR = 1.95, 95%CI = 1.19-3.20), respectively. Compared to insomnia with objective normal sleep duration, ISSD was associated with significantly higher pooled OR of prevalent hypertension (pooled OR = 1.94, 95%CI = 1.29-2.92) and pooled RR for incident hypertension (pooled RR = 2.07, 95%CI = 1.47-2.90), respectively. Furthermore, normal sleepers with objective short sleep duration were not associated with either prevalent (pooled OR = 1.21, 95%CI = 0.84-1.75) or incident (pooled RR = 0.97, 95%CI = 0.81-1.17) hypertension compared to NNSD. Our findings suggest that ISSD is a more severe phenotype of the disorder associated with a higher risk of hypertension. Objective short sleep duration might be a valid and clinically useful index of insomnia's impact on cardiovascular health.

High stability of EEG spectral power across polysomnography and multiple sleep latency tests in good sleepers and chronic insomniacs.

To assess the stability of electroencephalographic (EEG) spectral features across overnight polysomnography (PSG) and daytime multiple sleep latency tests (MSLTs) in chronic insomniacs (CIs) and normal controls (NCs). A total of 20 NCs and 22 CIs underwent standard PSG and MSLTs. Spectral analyses were performed on EEG data from PSG and MSLTs and absolute and relative power in central, frontal and occipital channels were obtained for wake (W) and non-rapid eye movement sleep stage 1 and 2 (N1, N2). Intraclass correlation coefficients (ICCs) were used to assess the stability of EEG spectral power across PSG and MSLTs for W, N1 and N2. The absolute power of all frequency bands except delta exhibited high stability across PSG and MSLTs in both NCs and CIs (ICCs ranged from 0.430 to 0.978). Although delta absolute power was stable in NCs during N1 and N2 stages (ICCs ranged from 0.571 to 0.835), it tended to be less stable in CIs during W and sleep stages (ICCs ranged from 0.042 to 0.807). We also observed lower stability of relative power compared to absolute power though the majority of relative power outcomes maintained high stability in both groups (ICCs in relative power ranged from 0.044 to 0.962). Most EEG spectral bandwidths across PSG and MSLT in W, N1 and N2 show high stability in good sleepers and chronic insomniacs. EEG signals from either an overnight PSG or a daytime MSLT may be useful for reliably exploring EEG spectral features during wakefulness or sleep.

Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review.

Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.

Association of food insecurity with successful aging among older Indians: study based on LASI.

PURPOSE: Whether food insecurity (FI), a social determinant of health, is linked with successful aging (SA) in the older generation remains uncertain. This study explored the association of FI with SA among older Indians. METHODS: Data were collected from the Longitudinal Ageing Study in India (LASI) wave 1 (2017-2018). Older adults (≥ 60 years) who completed both the FI and the SA surveys were selected. FI was indicated by the lack of access to enough food in the past year. SA was determined by five components: (1) low probability of diseases; (2) low probability of disability; (3) high cognitive functionality; (4) low probability of depression; and (5) active social engagement. The association of FI and SA was assessed using multivariable logistic regression adjusted for potential covariates. Subgroup analyses were performed to evaluate interactions with age, sex, alcohol use, smoking, and place of residence. RESULTS: 27,579 participants met the eligibility criteria. Overall prevalence was 7.13% for FI and 19.41% for SA. Following full adjustment, FI was inversely associated with SA (OR 0.56; 95% CI 0.49-0.65) and with each of SA's five components. No significant interactions of FI and SA were observed in subgroup analyses stratified by age, sex, alcohol use, smoking, or place of residence. CONCLUSIONS: FI was inversely associated with SA among older Indians. These findings need to be validated by future studies which should also explore potential underlying mechanisms, and whether interventions decreasing FI might increase SA.

Oxidative Stress Promotes Liver Cancer Metastasis via RNF25-Mediated E-Cadherin Protein Degradation.

Loss of E-cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its ß catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25-catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress-induced ECAD degradation promotes tumor metastasis of HCC.

The Epworth sleepiness scale may have more advantages than the multiple sleep latency test in assessing sleepiness in patients with obstructive sleep apnea.

This study aimed to analyze the brain function of severe obstructive sleep apnea patients with various sleepiness assessment methods and explore the brain imaging basis for the differences between these methods. This study included 30 severe obstructive sleep apnea patients and 19 healthy controls. Obstructive sleep apnea patients were divided into a subjective excessive daytime sleepiness group and a subjective non-excessive daytime sleepiness group according to the Epworth sleepiness scale. Moreover, they were divided into an objective excessive daytime sleepiness group and an objective non-excessive daytime sleepiness group according to the multiple sleep latency test. The fractional amplitude of low-frequency fluctuation was used to assess the features of brain function. Compared with healthy controls, participants in the subjective excessive daytime sleepiness group exhibited higher fractional amplitude of low-frequency fluctuation signals in the right thalamus, left cerebellar lobe 6, left putamen, and pallidum. Participants in the objective excessive daytime sleepiness group showed higher fractional amplitude of low-frequency fluctuation signals in the right thalamus and lower fractional amplitude of low-frequency fluctuation signals in the right superior frontal gyrus, the dorsolateral and superior frontal gyrus, and the medial orbital. We concluded that the thalamus may be involved in subjective and objective sleepiness regulation. Functional abnormalities in the putamen and pallidum may be involved in subjective sleepiness, whereas the frontal lobe may be involved in objective sleepiness.

Polysomnographic findings of myotonic dystrophy type 1/type 2: evidence from case-control studies.

STUDY OBJECTIVES: This study explores polysomnographic and multiple sleep latency test (MSLT) differences between myotonic dystrophy type 1/type 2 (DM1/DM2) patients and controls. METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, and Web of Science from inception to Aug 2023. RESULTS: Meta-analyses revealed significant reductions in sleep efficiency, N2 percentage, mean SpO2, and MSLT measured mean sleep latency, and increases in N3 sleep, wake time after sleep onset, apnea hypopnea index, and periodic limb movement index in DM1 patients compared with controls. However, any differences of polysomnographic sleep change between DM2 patients and controls could not be established due to limited available studies. CONCLUSIONS: Multiple significant polysomnographic abnormalities are present in DM1. More case-control studies evaluating polysomnographic changes in DM2 compared with controls are needed.

[Application of Polysomnography in Common Neurodegenerative Diseases].

At present, the etiology and pathogenesis of most neurodegenerative diseases are still not fully understood, which poses challenges for the prevention, diagnosis, and treatment of these diseases. Sleep disorders are one of the common chief complaints of neurodegenerative diseases. When patients suffer from comorbid sleep disorder and neurodegenerative diseases, the severity of their condition increases, the quality of their life drops further, and the difficulty of treatment increases. A large number of studies have been conducted to monitor the sleep of patients with neurodegenerative diseases, and it has been found that there are significant changes in their polysomnography (PSG) results compared to those of healthy control populations. In addition, there are also significant differences between the PSG findings of patients with different neurodegenerative diseases and the differences are closely associated with the pathogenesis and development of the disease. Herein, we discussed the characteristics of the sleep structure of patients with Parkinson's disease, Alzheimer's disease, Huntington's disease, and dementia with Lewy bodies and provided a brief review of the sleep disorders and the PSG characteristics of these patients. The paper will help improve the understanding of the pathogenesis and pathological changes of neurodegenerative diseases, clarify the relationship between sleep disorders and these diseases, improve clinicians' further understanding of these diseases, and provide a basis for future research.

Factors influencing the effectiveness of digital cognitive behavioural therapy for chronic insomnia in clinical practice.

Digital cognitive behavioural therapy for chronic insomnia (D-CBT-I) has been shown to be as efficacious as traditional CBT-I. However, not all patients achieve insomnia remission after treatment. We explored the factors influencing the effectiveness of D-CBT-I in a clinical practice. A total of 414 Asian chronic insomniacs were studied during a 6 week D-CBT-I intervention. All patients were assessed at baseline and posttreatment and were determined to be remitters or non-remitters, responders or non-responders by posttreatment criteria; Insomnia Severity Index (ISI <8) or ISI reduction ≥8, to examine whether remission and response status were associated with patient baseline characteristics. The average baseline ISI score in all subjects was 16.29 points. At posttreatment, 192 (46.4%) patients achieved ISI remission and 218 (52.7%) patients demonstrated an ISI response. An increased baseline early morning awakening time and ISI score were independently associated with a lower odds for remission (OR, 0.995 and 0.991, respectively). Increased baseline Patients Health Questionnaire-9 score was independently associated with higher odds for response (OR, 1.114). Our results suggest that D-CBT-I can be recommended as the first-line treatment for chronic insomnia, particularly in insomniacs with milder insomnia symptoms and more severe depressive symptoms. Meanwhile, the effectiveness of D-CBT-I was adversely affected by longer early morning awakening time and higher insomnia severity at pretreatment, which may be improved by more intense intervention and greater therapeutic support or by traditional CBT-I.

The association between polluted fuel use and self-reported insomnia symptoms among middle-aged and elderly Indian adults: a cross-sectional study based on LASI, wave 1.

BACKGROUND: Insomnia predisposes the aging population to reduced quality of life and poor mental and physical health. Evidence of the association between polluted fuel use and insomnia symptoms is limited and is non-existent for the Indian population. Our study aimed to explore the link between polluted fuel use and insomnia symptoms in middle-aged and older (≥ 45 years) Indian populations. METHODS: We utilized data from nationally representative Longitudinal Aging Study in India (LASI) Wave 1. Participants with complete information on fuel use, insomnia symptoms, and covariates were included. Insomnia symptoms were indicated by the presence of at least one of three symptoms: difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), or early morning awakening (EMA), ≥ 5 times/week. Survey-weighted multivariable logistic regression analyses were conducted to evaluate the association between polluted fuel use and insomnia symptoms. We also assessed the interaction of association in subgroups of age, gender, BMI, drinking, and smoking status. RESULTS: Sixty thousand five hundred fifteen participants met the eligibility criteria. Twenty-eight thousand two hundred thirty-six (weighted percentage 48.04%) used polluted fuel and 5461 (weighted percentage 9.90%) reported insomnia symptoms. After full adjustment, polluted fuel use was associated with insomnia symptoms (OR 1.16; 95%CI 1.08-1.24) and was linked with DIS, DMS, and EMA (OR 1.14; 95%CI 1.05-1.24, OR 1.12; 95%CI 1.03-1.22, and OR 1.15; 95%CI 1.06-1.25, respectively). No significant interactions for polluted fuel use and insomnia symptoms were observed for analyses stratified by age, sex, BMI, drinking, or smoking. CONCLUSIONS: Polluted fuel use was positively related to insomnia symptoms among middle-aged and older Indians. Suggestions are offered within this article for further studies to confirm our results, to explore underlying mechanisms, and to inform intervention strategies.

The insensitivity of sleep to an unfamiliar sleeping environment in patients with insomnia disorder.

BACKGROUND: Sleeping in an unfamiliar environment, such as a sleep laboratory, is thought to disturb sleep in healthy individuals and could express a hyperarousal state called the first night effect. Insomnia disorder (ID) is a highly prevalent health problem characterized by increased arousal during the night and daytime. Whether or not a similar phenomenon occurs in patients with ID is unclear. This study aimed to investigate the effect of an unfamiliar environment on the sleep of patients with ID. METHODS: In an unfamiliar sleep laboratory, polysomnographic recording testing was performed for two consecutive nights in patients with ID and age- and sex-matched healthy control subjects (HC). We collected sleep diaries and questionnaires regarding sleep, medical conditions, psychological status, and health history. Sleep continuity and architecture in both groups were compared and analyzed for two consecutive nights. RESULTS: Participants with ID (n = 39)  and HC (n = 35) demonstrated differentially poor sleep on laboratory adaptation after exposure to the sleep laboratory. Patients with ID had longer rapid eye movement (REM) latency on the first night than on the second sleep night. HC showed increased duration and percentage of N1, decreased duration and percentage of N3, and decreased REM percentage during initial nights compared to subsequent nights. The other sleep variables showed no differences between the first and second sleep nights in patients with ID and HC. CONCLUSIONS: An unfamiliar sleep environment does not aggravate the disruption of sleep continuity and sleep architecture but only affects the REM latency in patients with ID compared with HC.

Black hairy tongue after alprazolam intake.

Key Clinical Message: A 31-year-old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of alprazolam. Abstract: Alprazolam is a widely used antidepressant and antianxiety drug. Mild to moderate side effect of alprazolam was commonly seen, including lethargy, dizziness, headache, dry mouth, nausea, fatigue, constipation, and blurred vision. In this case, we reported a patient developed black hairy tongue after alprazolam intake, and her symptom resolved after 10-day discontinuation of alprazolam. This rare adverse event should be of concern to clinicians. This is the first paper to report an alprazolam-induced BHT. This rare side effect of alprazolam should be concern of clinicians; we hope our report will promote the understand of BHT and acknowledge clinicians of this rare side effect of alprazolam.

Clinical, polysomnographic, and heart rate variability in highland obstructive sleep apnea patients responding to one-night nocturnal oxygen supplementation: A post-hoc analysis from a randomized, crossover trial.

OBJECTIVE: /Background: This study aimed to explore the clinical, polysomnographic, and heart rate variability (HRV) characteristics of highland obstructive sleep apnea (OSA) patients receiving one-night nocturnal oxygen supplementation (NOS) and to identify factors predicting response. PATIENTS/METHODS: Thirty-four highland OSA patients living in Shangri-La were randomly assigned to receive NOS and sham oxygen in a randomized, placebo-controlled, crossover trial. Clinical assessments, polysomnography, and HRV were measured. A responder was defined as a ≥50% reduction in apnea-hypopnea index (AHI) with NOS compared with sham oxygen. RESULTS: Eighteen participants responded and 16 did not respond, with a median (interquartile range [IQR]) age of 46.5 (36.5-53.0) and 48.0 (44.3-53.3) years, respectively. The median treatment effect (95% CI) on total AHI was -23.2/h (-30.0 to -17.5) and -12.0/h (-16.6 to -7.6) in responders and non-responders (p = 0.004), with similar effects on oxygen desaturation index. The mean OAH duration was prolonged by 7 s in responders together with improved sleep quality and daytime blood pressure. The mean OAH duration at baseline predicted responses to NOS with a sensitivity and specificity of 88.9% and 68.7% (AUC 0.809) at a cut-off point of 24.9 s. Changes in HRV parameters were negatively correlated with changes in mean oxygen saturation and daytime systolic blood pressure only in responders. CONCLUSIONS: NOS significantly improved OSA severity and clinical outcomes in responders, which was related to improvements in parasympathetic activity. Highlanders with shorter mean OAH may be suitable candidates for NOS. These findings provide new information about tailored treatment strategies for highland OSA patients.

Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis is poorly understood. The heritability estimate of MDD is 30-40%, suggesting that genetics alone do not account for most of the risk of major depression. Another factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life stress. Recent studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic modifications. These epigenetic modification alterations contribute to abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission and neuroglia dysfunction, which are involved in the pathophysiology of MDD. Furthermore, epigenetic marks have been associated with the diagnosis and treatment of MDD. The evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD, and may identify new therapeutic targets. Here, we review preclinical and clinical epigenetic findings, including DNA methylation, histone modification, noncoding RNA, RNA modification, and chromatin remodeling factor in MDD. In addition, we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.

A physical understanding and quantification for the regulation of orexin on sleep.

The orexinergic neurons located in the lateral hypothalamus play a vital role in maintaining wakefulness and regulating sleep stability. Previous research has demonstrated that the absence of orexin (Orx) can trigger narcolepsy, a condition characterized by frequent shifts between wakefulness and sleep. However, the specific mechanisms and temporal patterns through which Orx regulates wakefulness/sleep are not fully understood. In this study, we developed a new model that combines the classical Phillips-Robinson sleep model with the Orx network. Our model incorporates a recently discovered indirect inhibition of Orx on sleep-promoting neurons in the ventrolateral preoptic nucleus. By integrating appropriate physiological parameters, our model successfully replicated the dynamic behavior of normal sleep under the influence of circadian drive and homeostatic processes. Furthermore, our results from the new sleep model unveiled two distinct effects of Orx: excitation of wake-active neurons and inhibition of sleep-active neurons. The excitation effect helps to sustain wakefulness, while the inhibition effect contributes to arousal, consistent with experimental findings [De Luca et al., Nat. Commun. 13, 4163 (2022)]. Moreover, we utilized the theory of potential landscapes to investigate the physical mechanisms underlying the frequent transitions observed in narcolepsy. The topography of the underlying landscape delineated the brain's capacity to transition between different states. Additionally, we examined the impact of Orx on barrier height. Our analysis demonstrated that a reduced level of Orx led to a bistable state with an extremely low threshold, contributing to the development of narcoleptic sleep disorder.

Sex differences in rapid eye movement sleep behavior disorder: A systematic review and meta-analysis.

Although rapid eye movement (REM) sleep behavior disorder (RBD) has been widely considered as a male-predominant parasomnia, the existing evidence for the sex difference in the risk of RBD in the general population was conflicting. The present study conducted a systematic review to explore the sex differences in the prevalence, comorbidities, clinical characteristics, and phenoconversion of RBD. One hundred thirty-five eligible studies were identified for the systematic review, and 133 were finally included in the meta-analysis. Males in the general population showed a trend for a higher risk of probable/possible RBD (pRBD), especially among the male older adults (aged ≥60). In the clinical populations, males showed a significantly higher risk of confirmed RBD, but not of pRBD. Among idiopathic RBD (iRBD) patients, males had a significantly earlier age onset of RBD compared with females. Male patients with Parkinson's disease (PD) had a higher risk of comorbid RBD. There was no significant sex difference in the risk of developing neurodegenerative diseases in iRBD patients. Large scale and prospective studies utilizing stringent diagnostic criteria for RBD are recommended to further verify the sex differences in RBD and to investigate the mechanism underlying the sex difference.