Pathological changes in the lenticulostriate artery indicate the mechanisms leading to intracranial hemorrhage in Moyamoya disease: a case report.

This case report details the pathological findings of a vessel wall identified as the bleeding point for intracranial hemorrhage associated with Moyamoya disease. A 29-year-old woman experienced intracranial hemorrhage unrelated to hyperperfusion following superficial temporal artery-middle cerebral artery bypass surgery. A pseudoaneurysm on the lenticulostriate artery (LSA) was identified as the causative vessel and subsequently excised. Examination of the excised pseudoaneurysm revealed a fragment of the LSA, with a disrupted internal elastic lamina and media degeneration. These pathological findings in a perforating artery, akin to the circle of Willis, provide insights into the underlying mechanisms of hemorrhage in Moyamoya disease.

Consensus statement on smoking cessation in patients with pain.

Smoking is closely associated with the development of various cancers and tobacco-related illnesses such as cardiovascular and respiratory disorders. However, data are scarce on the relationship between smoking and both acute and chronic pain. In addition to nicotine, tobacco smoke contains more than 4000 different compounds. Although nicotine is not the sole cause of smoking-induced diseases, it plays a critical role in pain-related pathophysiology. Despite the acute analgesic effects of nicotine, long-term exposure leads to tolerance and increased pain sensitivity due to nicotinic acetylcholine receptor desensitization and neuronal plastic changes. The purpose of smoking cessation interventions in smoking patients with pain is primarily not only to reduce their pain and associated limitations in activities of daily living, but also to improve the outcomes of underlying pain-causing conditions and reduce the risks of tobacco-related disorders. This statement aims to summarize the available evidence on the impact of smoking on pain and to inform medical professionals of the significance of smoking cessation in patients with pain.

Effects of Cognitive Behavioral Therapy for Insomnia on Subjective-Objective Sleep Discrepancy in Patients with Primary Insomnia: a Small-Scale Cohort Pilot Study.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia METHODS: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1-2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I. RESULTS: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy. CONCLUSIONS: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies.

Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats.

Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the PFC, but not in the NAcc or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area were observed in the offspring exposed to prenatal undernutrition and were mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the NAcc or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior, and its injection using liposome is a potential therapeutic approach for cognitive impairment.SIGNIFICANCE STATEMENT Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and the activity was circumscribed to the center area for a long time period, as in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment.

A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia.

Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10-9, odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10-18) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.

New susceptibility variants to narcolepsy identified in HLA class II region.

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

Aberrant Monoaminergic System in Thyroid Hormone Receptor-ß Deficient Mice as a Model of Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Thyroid hormone receptors are divided into 2 functional types: TRα and TRß. Thyroid hormone receptors play pivotal roles in the developing brain, and disruption of thyroid hormone receptors can produce permanent behavioral abnormality in animal models and humans. METHODS: Here we examined behavioralchanges, regional monoamine metabolism, and expression of epigenetic modulatory proteins, including acetylated histone H3 and histone deacetylase, in the developing brain of TRα-disrupted (TRα (0/0) ) and TRß-deficient (TRß (-/-) ) mice. Tissue concentrations of dopamine, serotonin (5-hydroxytryptamine) and their metabolites in the mesocorticolimbic pathway were measured. RESULTS: TRß (-/-) mice, a model of attention-deficit/hyperactivity disorder, showed significantly high exploratory activity and reduced habituation, whereas TRα (0/0) mice showed normal exploratory activity. The biochemical profiles of dopamine and 5-hydroxytryptamine showed significantly low dopamine metabolic rates in the caudate putamen and nucleus accumbens and overall low 5-hydroxytryptamine metabolic rates in TRß (-/-) mice, but not in TRα (0/0) mice. Furthermore, the expression of acetylated histone H3 was low in the dorsal raphe of TRß (-/-) mice, and histone deacetylase 2/3 proteins were widely increased in the mesolimbic system. CONCLUSIONS: These findings suggest that TRß deficiency causes dysfunction of the monoaminergic system, accompanied by epigenetic disruption during the brain maturation process.

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.

[Difficult Airway Management of a Patient with the Ossification of Anterior Longitudinal Ligament].

We report a case of difficult airway management (DAM) with the ossification of anterior longitudinal ligament (OALL). A 66-year-old man complained of pharyngeal discomfort. He was diagnosed with OALL, and planned to have a surgery under general anesthesia. We expected DAM due to the limitation of cervical mobility and airway obstruction caused by OALL. We succeeded in awake intubation with video laryngoscope and tracheal tube introducer.

Association of sleep-disordered breathing with decreased cognitive function among patients with dementia.

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type-4 portable monitor, is suitable. In this study, a type-4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep-disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep-disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early-stage dementia.

The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study.

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Plaque Ulcerations are Associated with Recurrence in Symptomatic Low-Grade Carotid Stenosis.

OBJECTIVE: Surgical indications for low-grade carotid stenosis have not yet been established. This study aimed to clarify the characteristics of low-grade carotid stenosis refractory to medical treatment. METHODS: We retrospectively analyzed 48 patients with symptomatic low-grade carotid stenosis (<50%). Recurrence was defined as an ipsilateral ischemic event in the symptomatic lesions during the follow-up period. Patient demographics and imaging findings were compared between the recurrence and nonrecurrence groups to investigate risk factors associated with medical treatment. RESULTS: The mean age was 74.1 (58-90 years), and the mean follow-up period was 35.4 months (2.0-97 months). Recurrence occurred in 15 of the symptomatic patients. Ulceration was significantly associated with recurrence under medical treatment (P = 0.001). The median time to recurrence was 26.1 months in patients with ulcers and 54.3 months in those without ulcers (P = 0.04). Pathological study with recurrence showed plaque rupture with multilayered lesions, indicating lesions refractory to medical treatment. CONCLUSIONS: In cases of low-grade carotid stenosis, lesions with ulcerations are likely refractory to medical therapy. Consideration of the indications for surgical treatment may be warranted for lesions with ulceration, even if the degree of stenosis is low.

A Review of Current Flow Diverters.

Flow diverter (FD) devices are new-generation stents placed in the parent artery at the aneurysmal neck to obstruct intra-aneurysmal blood flow, thus favoring intra-aneurysmal thrombosis. In Japan, about eight years have passed since health insurance approval was granted for FD devices, and FD placement to treat aneurysms has become widespread. Treatment indications have also been expanded with the introduction of novel devices. At present, three types of FD (Pipeline, FRED, and Surpass Streamline) are available in Japan. This report represents a compilation of available FD technologies and describes the current consensus on this treatment.

[Treatment of psychiatric symptoms in schizophrenia spectrum disorders with comorbid sleep apnea syndrome: a case report].

Sleep apnea syndrome (SAS) is characterized by apnea and hypopnea during sleep. SAS manifests various symptoms, and can become a risk factor for a variety of diseases. Typical psychiatric presentations of SAS are depressive symptoms, and those resembling negative symptoms in schizophrenia. We report two patients with schizophrenia spectrum disorders. Both patients showed the partial improvement of psychiatric symptoms with pharmacotherapy. After diagnosing comorbid SAS and subsequent treatment with continuous positive airway pressure (CPAP), the psychiatric symptoms improved. The first case was a 54-year-old woman, who presented with auditory hallucinations and delusions and was diagnosed with schizophrenia at 32 years of age. Her positive symptoms responded immediately to medication; however, her negative symptoms persisted despite switching to atypical antipsychotics. We diagnosed her with SAS using pulse oximetry and portable polysomnography (PSG), and, after treatment with CPAP, her fatigue and shallow sleep improved, as well as her quality of life (QOL). The second case was is a 61-year-old man, who presented with delusions of persecution and was diagnosed with delusional disorder at 49 years of age. His delusional symptoms fluctuated under medication, and repeatedly worsened under stressful situations. We suspected SAS as a Complicating factor, and diagnosed him with severe SAS using PSG. After treatment with CPAP, his hypertension and delusions of persecution improved. Screening for SAS is available in psychiatric hospitals and outpatient clinics. We believe that the possibility of comorbid SAS in psychiatric patients should be more widely acknowleged in clinical psychiatry.

Gender Disparities in First Authorship at Three Medical Universities in an Area Affected by the Great East Japan Earthquake.

The Great East Japan Earthquake that occurred on March 11, 2011, was one of the largest natural disasters in modern times. Publication in medical journals is important aspects of the academic promotion process, and is thus important for all scientists. However, little is known about whether and how substantial natural disasters affect gender disparities in academic productivity in disaster-affected areas. We hypothesized that the Great East Japan Earthquake widened the existing disparities in scientific publishing between male and female researchers. To test this hypothesis, this retrospective observational study using existing databases was conducted. We extracted from the MEDLINE database all types of biomedical articles published from March 11, 2007, to March 11, 2015, by three medical universities in a disaster-affected area of Japan. Differences in the proportion of female first authorship during the 4 years before and after the Great East Japan Earthquake were compared. A total of 5,873 papers were analyzed. The proportion of female first authors significantly declined after the Great East Japan Earthquake (20.5% vs. 14.1%; odds ratio 0.64; 95% confidence interval 0.56-0.73). A similar trend was identified across all prespecified subgroups, including clinical department; original article; public medical university; and prestigious journal with impact factor >6. Reference data from two medical universities minimally affected by the Great East Japan Earthquake showed the opposite trend. These results collectively suggest that large natural disasters can reinforce existing gender disparities in first authorship in biomedicine.

Correction to: Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography.

[This corrects the article DOI: 10.1007/s41105-022-00421-5.].

Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography.

Automatic algorithms are a proposed alternative to manual assessment of polysomnography data for analyzing sleep structure; however, none are acceptably accurate for clinical use. We investigated the feasibility of an automated sleep stage scoring system called Sleep Scope, which is intended for use with portable 1-channel electroencephalograph, and compared it with the traditional polysomnography scoring method. Twenty-six outpatients and fourteen healthy volunteers underwent Sleep Scope and polysomnography assessments simultaneously. Polysomnography records were manually scored by three sleep experts. Sleep Scope records were scored using a dedicated auto-staging algorithm. Sleep parameters, including total sleep time, sleep latency, wake after sleep onset, and sleep efficiency, were calculated. The epoch-by-epoch pairwise concordance based on the classification of sleep into five stages (i.e., wake, rapid eye movement, N1, N2, and N3) was also evaluated after validating homogeneity and bias between Sleep Scope and polysomnography. Compared with polysomnography, Sleep Scope seemed to overestimate sleep latency by approximately 3 min, but there was no consistent tendency in bias in other sleep parameters. The Κ values ranged from 0.66 to 0.75 for experts' inter-rater polysomnography scores and from 0.62 to 0.67 for Sleep Scope versus polysomnography scores, which indicated sufficient agreement in the determination of sleep stages based on the Landis and Koch criteria. We observed sufficient concordance between Sleep Scope and polysomnography despite lower concordance in sleep disorder patients. Thus, this auto-staging system might serve as a novel clinical tool for reducing the time and expenses required of medical staff and patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00421-5.

Transdiagnostic association between subjective insomnia and depressive symptoms in major psychiatric disorders.

In psychiatric disorders, comorbid depressive symptoms are associated with clinically important issues such as reduced quality of life, a poor prognosis, and increased suicide risk. Previous studies have found a close relationship between insomnia and depressive symptoms in major depressive disorder (MDD), and that actively improving insomnia heightens the improvement of depressive symptoms. This study aimed to investigate whether the association between insomnia and depressive symptoms is also found in other psychiatric disorders besides MDD. The subjects were 144 patients with MDD (n = 71), schizophrenia (n = 25), bipolar disorder (n = 22), or anxiety disorders (n = 26). Sleep status was assessed subjectively and objectively using the Athens Insomnia Scale (AIS) and sleep electroencephalography (EEG), respectively. Sleep EEG was performed using a portable EEG device. Depressive symptoms were assessed using the Beck Depression Inventory. Subjective insomnia, as defined by the AIS, was associated with depressive symptoms in all disorders. Moreover, in schizophrenia, a relation between depressive symptoms and insomnia was also found by objective sleep assessment methods using sleep EEG. Our findings suggest that the association between subjective insomnia and depressive symptoms is a transdiagnostic feature in major psychiatric disorders. Further studies are needed to clarify whether therapeutic interventions for comorbid insomnia can improve depressive symptoms in major psychiatric disorders, similar to MDD.

Exploring the role of empathy in prolonged grief reactions to bereavement.

Grief reactions to the bereavement of a close individual could involve empathy for pain, which is fundamental to social interaction. To explore whether grief symptoms interact with social relatedness to a person to whom one directs empathy to modulate the expression of empathy, we administered an empathy task to 28 bereaved adults during functional magnetic resonance imaging, in which participants were subliminally primed with facial stimuli (e.g., faces of their deceased or living relative, or a stranger), each immediately followed by a visual pain stimulus. Individuals' grief severity promoted empathy for the pain stimulus primed with the deceased's face, while it diminished the neural response to the pain stimulus primed with the face of either their living relative or a stranger in the medial frontal cortex (e.g., the right dorsal anterior cingulate cortex). Moreover, preliminary analyses showed that while the behavioral empathic response was promoted by the component of "longing" in the deceased priming condition, the neural empathic response was diminished by the component of "avoidance" in the stranger priming condition. Our results suggest an association between grief reactions to bereavement and empathy, in which grief symptoms interact with interpersonal factors to promote or diminish empathic responses to others' pain.