Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Insomnia in Adults: A Systematic Review and Component Network Meta-Analysis.

Importance: Chronic insomnia disorder is highly prevalent, disabling, and costly. Cognitive behavioral therapy for insomnia (CBT-I), comprising various educational, cognitive, and behavioral strategies delivered in various formats, is the recommended first-line treatment, but the effect of each component and delivery method remains unclear. Objective: To examine the association of each component and delivery format of CBT-I with outcomes. Data Sources: PubMed, Cochrane Central Register of Controlled Trials, PsycInfo, and International Clinical Trials Registry Platform from database inception to July 21, 2023. Study Selection: Published randomized clinical trials comparing any form of CBT-I against another or a control condition for chronic insomnia disorder in adults aged 18 years and older. Insomnia both with and without comorbidities was included. Concomitant treatments were allowed if equally distributed among arms. Data Extraction and Synthesis: Two independent reviewers identified components, extracted data, and assessed trial quality. Random-effects component network meta-analyses were performed. Main Outcomes and Measures: The primary outcome was treatment efficacy (remission defined as reaching a satisfactory state) posttreatment. Secondary outcomes included all-cause dropout, self-reported sleep continuity, and long-term remission. Results: A total of 241 trials were identified including 31 452 participants (mean [SD] age, 45.4 [16.6] years; 21 048 of 31 452 [67%] women). Results suggested that critical components of CBT-I are cognitive restructuring (remission incremental odds ratio [iOR], 1.68; 95% CI, 1.28-2.20) third-wave components (iOR, 1.49; 95% CI, 1.10-2.03), sleep restriction (iOR, 1.49; 95% CI, 1.04-2.13), and stimulus control (iOR, 1.43; 95% CI, 1.00-2.05). Sleep hygiene education was not essential (iOR, 1.01; 95% CI, 0.77-1.32), and relaxation procedures were found to be potentially counterproductive(iOR, 0.81; 95% CI, 0.64-1.02). In-person therapist-led programs were most beneficial (iOR, 1.83; 95% CI, 1.19-2.81). Cognitive restructuring, third-wave components, and in-person delivery were mainly associated with improved subjective sleep quality. Sleep restriction was associated with improved subjective sleep quality, sleep efficiency, and wake after sleep onset, and stimulus control with improved subjective sleep quality, sleep efficiency, and sleep latency. The most efficacious combination-consisting of cognitive restructuring, third wave, sleep restriction, and stimulus control in the in-person format-compared with in-person psychoeducation, was associated with an increase in the remission rate by a risk difference of 0.33 (95% CI, 0.23-0.43) and a number needed to treat of 3.0 (95% CI, 2.3-4.3), given the median observed control event rate of 0.14. Conclusions and Relevance: The findings suggest that beneficial CBT-I packages may include cognitive restructuring, third-wave components, sleep restriction, stimulus control, and in-person delivery but not relaxation. However, potential undetected interactions could undermine the conclusions. Further large-scale, well-designed trials are warranted to confirm the contribution of different treatment components in CBT-I.

Hyoro-zeme in the Battle for Tottori Castle: The first description of refeeding syndrome in Japan.

Eating after a period of starvation can cause refeeding syndrome, a fatal condition caused by a shift in fluids and electrolytes that can result in sudden death. The Battle for Tottori Castle (1581) during the Warring States Period of Japan, which witnessed the use of hyoro-zeme, the tactic of intentionally starving a besieged enemy, was followed by a dramatic episode of mass death among starving soldiers not from fighting but from eating; accounts from the period relate that many of the besieged soldiers survived the hyoro-zeme only to die soon afterwards when they were fed immediately after surrendering. We herein reviewed the Japanese historical records of the Battle for Tottori Castle and hypothesized that the hyoro-zeme episode they recount is possibly the oldest description of refeeding syndrome to be documented in Japan. Our investigation revealed sufficient evidence that refeeding syndrome was the cause of the mass deaths reported after the famous battle.

2,4,5,7,9,10-Hexaethynylpyrenes: Synthesis, Properties, and Self-Assembly.

A series of 2,4,5,7,9,10-hexaethynylpyrenes was synthesized using 2,7,9,10-tetrabromopyrene-4,5-dione as the key intermediate. The effects of the position and number of the ethynyl groups on the physicochemical properties of the corresponding pyrenes were clarified by comparison with 4,5,9,10-tetraethynylpyrene and 2,7-diethynylpyrene derivatives. The prepared hexaethynylpyrenes that bear benzene moieties self-assemble via π-π stacking in solution and/or the condensed phase.

Relationship between patellar mobility and patellofemoral joint cartilage degeneration after anterior cruciate ligament reconstruction.

Patellofemoral cartilage degeneration is a potential complication of anterior cruciate ligament reconstruction (ACLR) surgery. Hypomobility of the patella in the coronal plane is often observed after ACLR. Few studies, however, have examined the relationship between cartilage degeneration in the patellofemoral joint and mobility after ACLR. The present study investigated 1) the coronal mobility of the patella after ACLR, 2) the relationship between patellar mobility and cartilage degeneration of the patellofemoral joint, and 3) the relationship between patellar mobility and knee joint function after ACLR. Forty patients who underwent medial hamstring-based ACLR participated in the study. Lateral and medial patellar displacements were assessed with a modified patellofemoral arthrometer, and the absolute values of the displacements were normalized to patient height. The International Cartilage Repair Society (ICRS) cartilage injury classification of the patellar and femoral (trochlear) surfaces, and the Lysholm Knee Scoring Scale were used to evaluate knee function. Lateral and medial patellar displacements were reduced compared with the non-operated knee at the second-look arthroscopy and bone staple extraction operation (second operation; 24.4 ± 7.9 months after ACLR, P<0.01). The ICRS grades of the patellofemoral joint (patella and trochlea) were significantly worse than those pre-ACLR. Neither lateral nor medial patellar mobility, however, were significantly correlated with the ICRS grade or the Lysholm score. Although patellar mobility at approximately 2 years after ACLR was decreased compared to the non-operated knee, small displacement of the patella was not related to cartilage degeneration or knee joint function at the time of the second operation.

Irritable bowel syndrome among Japanese adolescents: A nationally representative survey.

BACKGROUND AND AIM: No nationally representative survey of irritable bowel syndrome (IBS) among adolescents has ever been performed in Japan. In the present study, we aimed to clarify the prevalence of IBS among Japanese adolescents and the factors associated with it. METHODS: The items related to the diagnostic criteria for IBS based on the Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders were included in a cross-sectional nationwide survey of "alcohol consumption and smoking habits among junior and senior high school students." The participating schools were sampled from among all junior and senior high schools in Japan using the cluster-sampling method, and self-administered questionnaires were sent to the selected schools by mail. Among 99 416 questionnaires that were collected, data from 98 411 valid responses were analyzed. RESULTS: The results showed that the prevalence of IBS was 18.6%. Although no sex difference was observed in the overall prevalence of IBS, the prevalence of diarrhea-predominant IBS was higher among boys than among girls, and the prevalence of constipation-predominant IBS was higher among girls than among boys. The prevalence of IBS increased with progression of the school grade, and there were the significant relationships between IBS and sleep-phase delay and insomnia symptoms. IBS was also significantly associated with poor mental health status. CONCLUSION: These results indicate that IBS is common among junior and senior high school students, and associated with lifestyle and mental health.

Salivary 3-methoxy-4-hydroxyphenylglycol increases after awakening in healthy young adults.

Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) may reflect central noradrenergic activity. In this study, we investigated salivary MHPG changes after awakening, and explored their relationships with cortisol and peripheral autonomic activity. The participants were 25 college students. Saliva samples were collected on awakening and 30 min after awakening to determine MHPG and cortisol. Ambulatory electrocardiograms were obtained to assess heart rate, cardiac sympathetic index (CSI), and cardiac vagal index (CVI) before and after awakening. MHPG levels increased significantly during the first 30 min after awakening. Similarly, cortisol, heart rate, and CSI increased during the 30 min after awakening, but changes in MHPG did not correlate with changes in cortisol, heart rate, CSI, and CVI during that period. This study demonstrated that salivary MHPG levels increase after awakening, in common with cortisol, heart rate, and cardiac sympathetic activity.

Factors affecting unhappiness at school among Japanese adolescents: an epidemiological study.

BACKGROUND: Unhappiness at school is one of the main reasons for truancy among adolescents. In order to assess this problem more thoroughly in the context of Japanese adolescents, the present study examined the associations between feelings of unhappiness at school and lifestyle habits, school life realities, and mental health status. METHOD: This study was designed as a cross-sectional survey. A self-administered questionnaire was provided to students enrolled in randomly selected junior and senior high schools throughout Japan. We calculated the percentages of both junior and senior high school students who felt unhappy at school based on factors related to school life, lifestyle habits, and mental health status. Multiple logistic regression analyses were performed in order to examine the associations between those factors and students' feelings of unhappiness at school. RESULTS: A total of 98,867 valid responses were analysed, 7.9% (Boys: 8.4%, Girls: 7.4%) of which came from students who responded that they felt unhappy at school. For both junior and senior high school students, the percentages of those who felt unhappy at school were significantly higher among those who had not yet decided on their future life course, who did not participate in extracurricular activities, did not eat breakfast every day, went to bed late, had used tobacco or alcohol in the previous 30 days, and had poor mental health compared with others. The results of multiple logistic regression analyses indicated that the adjusted odds ratios for feeling unhappy at school with regard to the above-mentioned factors were significantly high for both junior and senior high school students. CONCLUSIONS: The present results suggest that school employees and administrators must provide health guidance to students, considering that irregular lifestyle habits, lower school engagement, smoking, drinking alcohol, and poor mental health status are all associated with maladaptation to school among adolescents.

Associations between sleep disturbance and alcohol drinking: A large-scale epidemiological study of adolescents in Japan.

In this study, we attempted to clarify the associations between various sleep disturbance symptoms and the frequency and amount of alcohol use among Japanese adolescents. This study was designed as a cross-sectional sampling survey. A self-administered questionnaire survey was administered to students enrolled in randomly selected junior and senior high schools throughout Japan. A total of 99,416 adolescents responded, and 98,867 questionnaires were subjected to analysis. The prevalence rates of sleep disturbance in the 30 days preceding the day of the survey were as follows: subjectively insufficient sleep (SIS) (boys: 37.6%, girls: 38.7%); short sleep duration (SSD) with less than 6 h of sleep (boys: 28.0%, girls: 33.0%); difficulty initiating sleep (DIS) (boys: 12.5%, girls: 14.1%); difficulty maintaining sleep (DMS) (boys: 10.1%, girls: 10.9%); and early morning awakening (EMA) (boys: 5.1%, girls: 5.0%). Adolescents reporting one or more symptoms of DIS, DMS, and EMA were classified as having insomnia, and its prevalence was 21.5%. The prevalence of each symptom of sleep disturbance increased significantly with the number of days on which alcohol was consumed in the previous 30 days and the amount of alcohol consumed per drinking session (p < 0.01). Multiple logistic regression analyses showed that the adjusted odds ratio (AOR) for each symptom of sleep disturbance, except SIS and EMA, tended to increase with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. The prevalence of sleep disturbance is particularly high among adolescents drinking alcohol. The risk of having each symptom of sleep disturbance, except SIS and EMA, increases with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. These findings reconfirm the need to eliminate underage drinking to ensure good sleep among adolescents.

Disorders of arousal and sleep-related bruxism among Japanese adolescents: a nationwide representative survey.

OBJECTIVE: The main objective of our study was to clarify the prevalence of disorders of arousal (confusional arousals, sleepwalking, sleep terrors) and sleep-related bruxism (teeth grinding) and their associated factors among Japanese adolescents. METHODS: Our study was designed as a cross-sectional sampling survey. The targets were students attending junior and senior high schools throughout Japan. The questionnaire asked for personal data and information on lifestyle, depressive state, and sleep status including the frequency of experiencing disorders of arousal and sleep-related bruxism. RESULTS: A total of 99,416 adolescents responded. The overall response rate was 63.7%, and 98,411 questionnaires were subjected to analysis. The prevalence of disorders of arousal was 7.1% (95% confidence interval [CI], 6.9-7.3%) among boys and 7.7% (95% CI, 7.5-7.9%) among girls. The prevalence of sleep-related bruxism was 2.3% (95% CI, 2.2-2.4%) among boys and 3.0% (95% CI, 2.8-3.2%) among girls. The factors associated with disorders of arousal were the grade in school, smoking habit, alcohol consumption, naptime (min), breakfast habit, participation in club activities, sleep duration, difficulty initiating sleep, nocturnal awakening, early morning awakening, subjective sleep assessment, snoring, decrease in positive feelings, and depression (all p<.001). The factors associated with sleep-related bruxism were gender, smoking habit, nocturnal awakening, snoring, early morning awakening, decrease in positive feelings, and depressive feelings (all p<.001). CONCLUSIONS: If disorders of arousal or sleep-related bruxism are observed in an adolescent, his or her smoking habit, alcohol consumption, sleep status, and depressive state should be considered.

Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification. FOP is caused by a gain-of-function mutation in ACVR1 encoding the bone morphogenetic protein type II receptor, ACVR1/ALK2. The mutant receptor causes upregulation of a transcriptional factor, Id1. No therapy is available to prevent the progressive heterotopic ossification in FOP. In an effort to search for clinically applicable drugs for FOP, we screened 1,040 FDA-approved drugs for suppression of the Id1 promoter activated by the mutant ACVR1/ALK2 in C2C12 cells. We found that that two antianginal agents, fendiline hydrochloride and perhexiline maleate, suppressed the Id1 promoter in a dose-dependent manner. The drugs also suppressed the expression of native Id1 mRNA and alkaline phosphatase in a dose-dependent manner. Perhexiline but not fendiline downregulated phosphorylation of Smad 1/5/8 driven by bone morphogenetic protein (BMP)-2. We implanted crude BMPs in muscles of ddY mice and fed them fendiline or perhexiline for 30 days. Mice taking perhexiline showed a 38.0 % reduction in the volume of heterotopic ossification compared to controls, whereas mice taking fendiline showed a slight reduction of heterotopic ossification. Fendiline, perhexiline, and their possible derivatives are potentially applicable to clinical practice to prevent devastating heterotopic ossification in FOP.

The association between use of mobile phones after lights out and sleep disturbances among Japanese adolescents: a nationwide cross-sectional survey.

STUDY OBJECTIVE: The objective of this study was to examine the association between the use of mobile phones after lights out and sleep disturbances among Japanese adolescents. DESIGN AND SETTING: This study was designed as a cross-sectional survey. The targets were students attending junior and senior high schools throughout Japan. Sample schools were selected by cluster sampling. Self-reported anonymous questionnaires were sent to schools for all students to fill out. PARTICIPANTS: A total of 95,680 adolescents responded. The overall response rate was 62.9%, and 94,777 questionnaires were subjected to analysis. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Daily mobile phone use, even if only for a brief moment every day, was reported by 84.4%. Moreover, as for use of mobile phones after lights out, 8.3% reported using their mobile phone for calling every day and 17.6% reported using it for sending text messages every day. Multiple logistic regression analysis showed that mobile phone use for calling and for sending text messages after lights out was associated with sleep disturbances (short sleep duration, subjective poor sleep quality, excessive daytime sleepiness, and insomnia symptoms) independent of covariates and independent of each other. CONCLUSION: This study showed that the use of mobile phones for calling and for sending text messages after lights out is associated with sleep disturbances among Japanese adolescents. However, there were some limitations, such as small effect sizes, in this study. More studies that examine the details of this association are necessary to establish strategies for sleep hygiene in the future.

Inflammatory effect of advanced glycation end products on human meniscal cells from osteoarthritic knees.

OBJECTIVE: To investigate the inflammatory effects of advanced glycation end-products (AGEs) through the receptor for AGE in meniscal cells from osteoarthritic knees, and examine effects of hyaluronan (HA) on AGE-induced inflammation. METHODS: Meniscal cells from human osteoarthritic knees were cultured with or without glycolaldehyde-AGE-bovine serum albumin and 800 kDa HA. The amount of prostaglandin E(2) (PGE(2)) protein was determined using an enzyme immunoassay system. Expression of cyclooxygenase (COX)-1, COX-2, membrane associated prostaglandin E synthase (mPGES)-1 and cytosolic PGES (cPGES) was analyzed by real-time reverse transcription polymerase chain reaction and western blotting. RESULTS: PGE(2) synthesis was significantly increased by AGEs, and AGE-induced PGE(2) production was attenuated by addition of HA. While COX-2 and mPGES-1 expression was significantly upregulated by AGEs, COX-1 and cPGES expression was not affected by AGE. AGE-stimulated COX-2 and mPGES-1 expression was attenuated by HA through CD44 (HA receptor). However, the changes in COX-1 and cPGES expression were almost negligible. CONCLUSION: In meniscal cells from osteoarthritic knees, AGEs increased the production of inflammatory mediators, including PGE(2), COX-2 and mPGES-1. Furthermore, HA could decrease AGE-induced production of PGE(2), COX-2 and mPGES-1 through CD44.

The cortisol awakening response and autonomic nervous system activity during nocturnal and early morning periods.

The current study focuses on autonomic nervous system activity during sleep as a physiological aspect of sleep quality, and investigated the associations between the cortisol awakening response (CAR) and autonomic activity during sleep and after awakening. Ambulatory electrocardiograms were obtained from 20 participants, who also provided saliva samples (at the time of awakening, and 30, 45, and 60 min after awakening) and rated the subjective quality of their sleep at home. Autonomic activity was assessed with the Lorenz plot indices, cardiac sympathetic index (CSI) and cardiac vagal index. Total salivary cortisol secretion after awakening was calculated as area under the curve with respect to ground (AUC(G)) and increase (AUC(I)). After controlling for confounding factors, including sleep duration and awakening time, cortisol AUC(G) and AUC(I) were both found to be negatively correlated with CSI during the 30 min before and after awakening: before (r = -0.526 and -0.601 respectively) and after (r = -0.540 and -0.493 respectively). Self-reported sleep quality was not associated with the CAR. These results suggest that the CAR is negatively affected by basal sympathetic activity immediately before and after awakening, but not affected by subjective sleep quality. Physiological arousals around the time of awakening might inhibit the CAR.