The effect of nonrestorative sleep on incident hypertension 1-2 years later among middle-aged Hispanics/Latinos.

BACKGROUND: Insomnia is known to be a major risk factor for incident hypertension. Nonrestorative sleep (NRS), which refers to insufficiently rested sleep, has reported to associate with various diseases. This study aimed to investigate the longitudinal association between insomnia-related symptoms including NRS and incident hypertension 1-2 years later by age group (young, 18-39 years and middle-age, 40-64 years) using existing cohort data involving Hispanics/Latinos. METHODS: This study included 1100 subjects who had participated in both the Hispanic Community Health Study/Study of Latinos and its follow-up study, the Sueño Ancillary Study, and met additional eligibility criteria. Incident hypertension was assessed by self-reported history and/or the use of antihypertensives. The Women's Health Initiative Insomnia Rating Scale (WHIIRS) was used to evaluate insomnia-related symptoms (difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, difficulty returning to sleep, and NRS). Logistic regression analyses were conducted to assess the degree to which insomnia-related symptoms at baseline predicted incident hypertension. RESULTS: Among the participants (64% middle-aged, 36% young adults), 140 (12.7%) developed hypertension during the follow-up period. Among the sleep-related symptoms, only NRS predicted incident hypertension after adjusting for sociodemographic factors and physical condition (odds ratio: 1.88, 95% confidence interval: 1.10-3.21, p = 0.022) in middle-aged adults. None of the insomnia-related symptoms were associated with incident hypertension in the young adults. No association was found between WHIIRS-defined insomnia (total score ≥ 9) and incident hypertension in middle-aged adults or young adults. CONCLUSION: The present findings suggest the importance of focusing on NRS to help prevent the development of hypertension in middle-aged adults.

Associations of nonrestorative sleep and insomnia symptoms with incident depressive symptoms over 1-2 years: Longitudinal results from the Hispanic Community Health Study/Study of Latinos and Sueño Ancillary Study.

BACKGROUND: Nonrestorative sleep (NRS), defined as insufficiently rested or refreshed sleep, is considered to play an important role in the development of depression. The aim of this study is to investigate the predictive ability of insomnia-related symptoms, including NRS, for incident depressive symptoms (DEPs) in a longitudinal manner. METHODS: We used data of 1196 samples aged 18-64 years who participated in both the Hispanic Community Health Study/Study of Latinos conducted in 2008-2010 and the follow-up study (Sueño Ancillary Study) conducted in 2010-2013. DEPs and insomnia-related symptoms (difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], early morning awakening [EMA], difficulty returning to sleep [DRS], and NRS) were evaluated by the 10-item Center for Epidemiologic Studies Depression Scale and the Women's Health Initiative Insomnia Rating Scale, respectively. A logistic regression analysis was used to evaluate the predictive ability of each insomnia-related symptom at baseline for incident DEPs in couple-years. RESULTS: In the univariate logistic regression analysis, all insomnia-related symptoms had significant associations with incident DEPs (DIS, odds ratio [OR] = 1.6; DMS, OR = 1.6; EMA, OR = 1.5; DRS, OR = 1.9; NRS, OR = 2.5). After adjusting for sociodemographic factors and the confounding effects of other insomnia-related symptoms, only NRS (OR = 2.2, 95% confidence interval = 1.4-3.5, p = .001) was significantly associated with incident DEPs. CONCLUSIONS: NRS was a risk factor for incident DEPs, which includes a predictive ability for other insomnia-related symptoms. Our results suggest that focusing on NRS is an effective strategy for preventing depression in public health promotions.

A Case of High Altitude Cerebral Edema With a Prolonged Motivational Deficit.

We report a case of prolonged motivational deficit as a sequela of high altitude cerebral edema (HACE), the most severe form of neuropsychiatric dysfunction arising from traveling to high altitude. Magnetic resonance imaging of the brain showed hyperintense lesions in the globi pallidi bilaterally on T2-weighted images. Single-photon emission computed tomography showed hypoperfusion in dorsolateral and orbital prefrontal cortices bilaterally and in the anterior cingulate cortex. This case suggests that a prolonged motivational deficit can occur in patients with HACE. The case may also suggest that HACE can cause network disturbances between the prefrontal cortex and the globi pallidi.

Severe fatigue due to valproate-induced hypothyroidism in a case of bipolar disorder.

BACKGROUND: Valproate-induced hypothyroidism is a rare condition and has been considered asymptomatic. Here, we report a case of bipolar I disorder who developed symptomatic valproate-induced hypothyroidism. CASE PRESENTATION: A 44-year-old woman with bipolar I disorder complained of severe fatigue after starting valproate. She showed a hormonal pattern of central hypothyroidism. Thyroid autoantibodies were negative, and no pituitary abnormality was seen on magnetic resonance imaging. After stopping valproate, her severe fatigue rapidly improved with normalizing thyroid function. CONCLUSIONS: Our case suggests that valproate-induced hypothyroidism should be considered when patients complain of excessive fatigue under treatment with valproate.

Impact of chronotype, insomnia symptoms, sleep duration, and electronic devices on nonrestorative sleep and daytime sleepiness among Japanese adolescents.

OBJECTIVES: Nonrestorative sleep (NRS) and excessive daytime sleepiness (EDS) are important indicators of daytime dysfunction. Electronic media use before bedtime greatly affects adolescent sleep quality. However, few studies have examined factors associated with these symptoms. Therefore, we aimed to investigate the impact of chronotype, electronic device use before bedtime, and insomnia symptoms on NRS and EDS in Japanese adolescents. METHODS: A web-based cross-sectional survey of 2067 adolescents was conducted in 2022 to mainly assess sleep-related issues (sleep duration, chronotype, insomnia symptoms, NRS, and EDS), time spent using electronic devices, physical activity, and mental health. RESULTS: We analyzed data of 1880 adolescents (age, 16.4 ± 0.8 years; males, 56.7%). NRS and EDS prevalence rates were 54.9% and 39.4%, respectively. In multivariate analysis, evening chronotype [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.58-2.89], difficulty initiating sleep (OR: 1.94, 95% CI: 1.43-2.64), <5 h sleep (OR: 1.77, 95% CI: 1.24-2.54), 5-6 h sleep (OR: 1.52, 95% CI: 1.20-1.93), and using electronic devices just before bedtime (OR: 1.48, 95% CI: 1.08-2.04) were associated with NRS. Evening chronotype (OR: 1.40, 95% CI: 1.07-1.82), early morning awakening (OR: 1.60, 95% CI: 1.02-2.50), using electronic devices just before bedtime (OR: 2.08, 95% CI: 1.48-2.93), and using electronic devices 30 min before bedtime (OR: 1.57, 95% CI: 1.07-2.29) were associated with EDS. CONCLUSION: Chronotype may be an important factor influencing NRS and EDS. Discontinuing electronic device use at least 30 min before bedtime could benefit affected adolescents.

Nonrestorative sleep is a risk factor for metabolic syndrome in the general Japanese population.

BACKGROUND: This longitudinal study aimed to investigate the effects of nonrestorative sleep on developing metabolic syndrome (MetS) and related diseases in a general Japanese middle-aged population. METHODS: Overall, 83,224 adults without MetS (mean age: 51.5 ± 3.5 years) from the Health Insurance Association in Japan were followed up for a maximum of 8 years between 2011 and 2019. The Cox proportional hazard method was used to determine whether nonrestorative sleep, assessed using a single-item question, was significantly associated with the respective development of MetS, obesity, hypertension, diabetes, and dyslipidemia. The MetS criteria were adopted by the Examination Committee for Criteria of Metabolic Syndrome in Japan. RESULTS: The mean follow-up duration was 6.0 years. The incidence rate of MetS was 50.1 person-years/1,000 during the study period. Data suggested that nonrestorative sleep was associated with MetS (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.08-1.16) and other disorders, such as obesity (HR: 1.07, 95% CI: 1.02-1.12), hypertension (HR: 1.07, 95% CI: 1.04-1.11), and diabetes (HR: 1.07, 95% CI: 1.01-1.12) but not with dyslipidemia (HR: 1.00, 95% CI: 0.97-1.03). CONCLUSIONS: Nonrestorative sleep is associated with the development of MetS and many of its core components in the middle-aged Japanese population. Therefore, assessing nonrestorative sleep may help identify individuals at a risk of MetS development.

Trends and socioeconomic inequities in insomnia-related symptoms among Japanese adults from 1995 to 2013.

BACKGROUND: Although insomnia prevalence is increasing in developed countries, little is known about trends in sleep problems among Japanese adults according to socioeconomic status. Therefore, we aimed to determine trends and socioeconomic inequalities in insomnia-related symptom (IRS) in Japan using nationally representative data. METHODS: The IRSs were based on past subjective sleeping difficulty. Using data from the Comprehensive Survey of Living Conditions for every 3 years from 1995 to 2013, we built multivariable Poisson regression models, with IRS as an outcome and survey year and socioeconomic status variables as explanatory variables. RESULTS: Data from 513,223 Japanese adults were analyzed. Age- and sex-adjusted IRS prevalence was the lowest in 1995, highest in 2007, and decreased from 2007 to 2013. The IRSs were more frequently reported in unemployed or self-employed individuals aged 20-64 years; those with the lowest household expenditure level, except among women aged ≥65 years; and those divorced, separated, or single, especially among women aged 20-64 years. LIMITATIONS: First, the repeated cross-sectional study design prevented the exclusion of the possibility of reversal of causality between factors. Second, data on insomnia-related lifestyle behaviors were unavailable. Third, the IRSs examined did not meet established clinical criteria for clinical insomnia. Fourth and fifth, information and selection biases could exist because of self-reported data and a small sample size, respectively. CONCLUSIONS: These results could aid in developing more effective prevention strategies for sleep problems and provide benchmarks for monitoring sleep health trends in Japan and other East Asian countries.

Differences in psychosocial factors and sleep study findings between delayed sleep-wake phase disorder and hypersomnia in teenagers.

Central hypersomnia (HS) and delayed sleep-wake phase disorder (DSWPD) appear commonly in adolescents, and they severely reduce quality of life and have an enormous impact on academic performance and other aspects of development. Although these disorders are thought to be considerably different in etiology, it is sometimes difficult to distinguish them because of their similar clinical features. This study aimed to compare psychosocial factors and sleep study findings between HS and DSWPD in teenagers. The clinical data of 89 teenagers who visited the psychiatric section of the Sleep Medicine Center of Nihon University Itabashi Hospital from January 2013 to December 2019 were analyzed. Psychosocial factors were evaluated at the first visit, and polysomnography (PSG) and the multiple sleep latency test (MSLT) were performed for patients deemed to require definitive diagnosis. Compared with patients with HS, those with DSWPD had a higher rate of mother's employment, introversion, adjustment problems, events that triggered the disorder, concurrent mental disorders, habitual lateness, and difficulty attending school or work. PSG did not show any differences in sleep parameters between the two disorders, except for sleep latency. On the MSLT, sleep latency was shorter in those with HS on the second, third, and fourth tests. The present results suggest that focusing on psychosocial factors could be useful for differential diagnosis of the two disorders that appear commonly in adolescents.

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.

Combined in silico and in vivo analyses reveal role of Hes1 in taste cell differentiation.

The sense of taste is of critical importance to animal survival. Although studies of taste signal transduction mechanisms have provided detailed information regarding taste receptor calcium signaling molecules (TRCSMs, required for sweet/bitter/umami taste signal transduction), the ontogeny of taste cells is still largely unknown. We used a novel approach to investigate the molecular regulation of taste system development in mice by combining in silico and in vivo analyses. After discovering that TRCSMs colocalized within developing circumvallate papillae (CVP), we used computational analysis of the upstream regulatory regions of TRCSMs to investigate the possibility of a common regulatory network for TRCSM transcription. Based on this analysis, we identified Hes1 as a likely common regulatory factor, and examined its function in vivo. Expression profile analyses revealed that decreased expression of nuclear HES1 correlated with expression of type II taste cell markers. After stage E18, the CVP of Hes1(-/) (-) mutants displayed over 5-fold more TRCSM-immunoreactive cells than did the CVP of their wild-type littermates. Thus, according to our composite analyses, Hes1 is likely to play a role in orchestrating taste cell differentiation in developing taste buds.

Association of insomnia symptoms and non-restorative sleep with Typus melancholicus: a Japanese general population survey.

This study aimed to investigate the association between insomnia symptoms and non-restorative sleep (NRS) in individuals with Typus melancholicus, a personality trait linked to depression, in the general population. We analyzed data from a Japanese cross-sectional survey of 2519 randomly sampled adults. Typus melancholicus was evaluated using a modified version of Kasahara's Typus melancholicus inventory (modified-KTM). Logistic regression analysis was used to examine the associations of insomnia symptoms and NRS with modified-KTM scores. We demonstrated that insomnia symptoms and NRS were both positively associated with modified-KTM scores. Our results provide evidence for an association between Typus melancholicus and insomnia.

Comparison of the efficacy and safety of quetiapine and lithium for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.

AIM: Pharmacological treatments recommended for bipolar depression are inconsistent across guidelines. We compared the efficacy and safety of antipsychotics and mood stabilizers for bipolar depression. METHODS: A systemic review and meta-analysis of randomized controlled trials comparing antipsychotics and mood stabilizers for bipolar depression was conducted based on a literature search of major electronic databases. RESULTS: Three studies comparing quetiapine with lithium were identified and analyzed; no other antipsychotic-mood stabilizer combinations were found. The meta-analysis revealed no significant differences between quetiapine and lithium for the following outcomes: (1) remission from depressive episodes (risk ratio [RR]: 1.80, 95% CI: 0.51-6.40, P = 0.36), (2) changes in depressive symptom (standardized mean difference: -0.22, 95% CI: -0.52-0.08, P = 0.15), (3) changes in social function (standardized mean difference: -0.00, 95% CI: -0.19-0.18, P = 0.98), (4) suicide-related events (odds ratio [OR]: 2.35, 95% CI: 0.40-13.65, P = 0.34), (5) severe adverse events (OR: 1.63, 95% CI: 0.51-5.20, P = 0.41), (6) dropouts due to adverse events (RR: 1.19, 95% CI: 0.76-1.87, P = 0.45, 7) dropout for any reasons (RR: 0.95, 95% CI: 0.74-1.22, P = 0.70). CONCLUSION: Although this study found no differences in the efficacy and safety of quetiapine and lithium for bipolar depression, a comprehensive comparison of antipsychotics and mood stabilizers was not performed. Further studies are needed to clarify which of these, not just quetiapine and lithium, is more useful for bipolar depression.

Differential effects of aging and cognitive decline on visual exploration behavior in the elderly.

Visual exploration disturbance has been examined in the elderly, mainly from the perspective of associations with cognitive function. However, it remains unknown whether this is a consequence of cognitive decline, age-related changes independent of cognitive decline, or both. In this study, 15 healthy elderly individuals were evaluated using two figure-matching tasks representing visual information processing (clock-matching and inverted clock-matching tasks). Cognitive functions were evaluated for each subject using the Mini-Mental State Examination (MMSE). Infrared eye-movement assessments were used to analyze eye movements during task performance. Behavioral analyses showed that age was associated with longer reaction time, while MMSE score was associated with higher accuracy on the inverted clock-matching task. Analyses of eye-movement parameters showed that MMSE score was negatively associated with a parameter indicating difficulty in the efficiency of visual exploration planning, while age was tended to be positively associated with the sum of saccade times in each trial, both predominantly on the inverted clock-matching task. Our approaches highlighted that age and cognitive decline are separately associated with eye-movement characteristics: cognitive decline is associated with difficulty in visual exploration planning, particularly in situations that require substantial visual working memory resources, whereas aging may be associated with oculomotor dysfunction.

Successful Combination Therapy of Trazodone and Fluvoxamine for Pica in Alzheimer's Disease: A Case Report.

Pica in Alzheimer's disease (AD) makes it difficult for caregivers to provide care. However, few effective medications have been reported for pica in AD. We report a case of AD with pica that was successfully improved by trazodone and fluvoxamine. An 80-year-old woman with AD was admitted to our hospital due to aggravated pica, including eating weeds in the facility's garden and eating a dishwashing sponge. Her pica was accompanied by oral tendency, prosopagnosia, and placidity. She took rivastigmine and memantine, but these were ineffective for her pica. She was given olanzapine and perospirone, but both were discontinued due to over-sedation and severe extrapyramidal symptoms, respectively. We then administered trazodone and fluvoxamine, both of which have demonstrated effectiveness for pica in frontotemporal dementia (FTD). Her pica behaviors then disappeared without daytime sleepiness. In this case, pica with oral tendency, which was accompanied by prosopagnosia and placidity, may be interpreted as a partial symptom of Klüver-Bucy syndrome (KBS). KBS is often seen in FTD, but also occurs in late-stage AD. Our case together with previous reports showing that trazodone and fluvoxamine were effective for pica in FTD suggest that the same common drug therapy may be successful in pica with oral tendency, regardless of the subtype of dementia.

[Metastatic renal tumor originating from thyroid cancer: a case report].

A 82-year-old female was referred to our department for close examination and treatment of a right renal tumor incidentally found by computed tomography. Her past history included partial thyroidectomy for follicular thyroid carcinoma 20 years earlier. Enhanced computed tomography showed a hypervascular mass with a diameter of 3 cm at the lower pole of the right kidney. We carried out radical nephrectomy for diagnosis of renal cell carcinoma. Pathological findings revealed a metastatic renal tumor of follicular thyroid carcinoma. It is rare to find metastatic renal tumors arising from thyroid carcinoma in clinical practice. Thirty cases have been reported in the Japanese literature.

Initial 3-year results of first human use of an in-body tissue-engineered autologous "Biotube" vascular graft for hemodialysis.

This study presents the initial 3-year results of the first in-human study of internal shunt restoration using completely autologous vascular grafts, "Biotubes," based on in-body tissue architecture. Biotubes (diameter, 6 mm; length, 7 cm) were prepared as autologous collagenous tubular tissues with approximately 0.5 mm wall thickness by embedding molds (two per patient), assembled with a silicone rod and a stainless steel pipe with many slits, into the patients' abdominal subcutaneous tissue for 2 months. Two female patients with end-stage renal disease were undergoing hemodialysis with a high probability of failure due to repeated stenosis every few months at the venous outflow regions over 1.5 years. Biotubes formed in both patients and were bypassed over the venous stenosis region of the arteriovenous shunt. After bypass with Biotubes without living cells, palpable thrill and typical turbulent flow pattern were observed by pulsed-wave Doppler. Follow-up angiography showed no signs of dilation or stenosis after implantation, and puncture could be performed easily without graft damage. In both cases, stenosis of Biotubes occurred after 3-4 months. In the first case, percutaneous transluminal angioplasty was not required for over 2 years after implantation even after the development of Biotube stenosis. In the second case, stenosis at the proximal anastomotic site of the Biotube became prominent, and percutaneous transluminal angioplasty was needed 7 months after implantation and then repeated at up to 2 years. This was the first human study successfully supporting the concept of internal shunt restoration for hemodialysis using an autologous Biotube.

Exploding Head Syndrome Accompanied by Repeating Panic Attacks: A Case Report.

To the best of our knowledge, we report here for the first time a case of exploding head syndrome (EHS) that caused repeating panic attacks. A 62-year-old woman experienced a sudden sensation of a loud noise just before going to sleep. The frequency of these episodes rapidly increased to multiple times per night, and she soon began to fear sleep, which led to the occurrence of nighttime panic attacks. She was diagnosed with EHS at our sleep clinic, and clonazepam was prescribed accompanied by reassurance about the benign nature of this syndrome. The intensity of the loud noise gradually reduced, and her fear of sleep and panic attacks disappeared at around the same time. In this report, we argue the importance of gaining further knowledge about EHS, including that about complicating psychiatric symptoms and that about its treatment.

Multimodal visual exploration disturbances in Parkinson's disease detected with an infrared eye-movement assessment system.

Parkinson's disease (PD) reportedly show disturbed visual exploration. However, whether this disturbance is due to dysfunctional visual information processing remains unclear. To clarify the effects of PD on visual information processing when exploring for targets and to compare disease effects with aging effects, we used an infrared eye-movement assessment system. Cognitively normal PD patients (n = 13), healthy age-matched (n = 17) and young controls (n = 36) participated in this study, and were evaluated using two figure-matching tasks representing visual information processing (clock-matching and inverted clock-matching tasks) and saccade tasks representing oculomotor function. With figure-matching tasks, PD patients showed significantly larger numbers of images watched in a single trial compared to healthy age-matched controls on the inverted clock-matching task. No aging effects was found in these variables. In contrast, no disease effect was apparent for reaction time, which was significantly longer in healthy age-matched controls than in healthy young controls. For saccade tasks, PD patients showed significantly smaller saccade size than healthy age-matched controls on the antisaccade task, but no aging effects were evident. Our approaches highlighted that visual exploration disturbance in PD may be due to dysfunctional visual information processing in addition to dysfunctional oculomotor processing. These disease effects may differ from aging effects.

Dephosphorylation of protamine 2 at serine 56 is crucial for murine sperm maturation in vivo.

The posttranslational modification of histones is crucial in spermatogenesis, as in other tissues; however, during spermiogenesis, histones are replaced with protamines, which are critical for the tight packaging of the DNA in sperm cells. Protamines are also posttranslationally modified by phosphorylation and dephosphorylation, which prompted our investigation of the underlying mechanisms and biological consequences of their regulation. On the basis of a screen that implicated the heat shock protein Hspa4l in spermatogenesis, we generated mice deficient in Hspa4l (Hspa4l-null mice), which showed male infertility and the malformation of sperm heads. These phenotypes are similar to those of Ppp1cc-deficient mice, and we found that the amount of a testis- and sperm-specific isoform of the Ppp1cc phosphatase (Ppp1cc2) in the chromatin-binding fraction was substantially less in Hspa4l-null spermatozoa than that in those of wild-type mice. We further showed that Ppp1cc2 was a substrate of the chaperones Hsc70 and Hsp70 and that Hspa4l enhanced the release of Ppp1cc2 from these complexes, enabling the freed Ppp1cc2 to localize to chromatin. Pull-down and in vitro phosphatase assays suggested the dephosphorylation of protamine 2 at serine 56 (Prm2 Ser56) by Ppp1cc2. To confirm the biological importance of Prm2 Ser56 dephosphorylation, we mutated Ser56 to alanine in Prm2 (Prm2 S56A). Introduction of this mutation to Hspa4l-null mice (Hspa4l -/-; Prm2 S56A/S56A) restored the malformation of sperm heads and the infertility of Hspa4l -/- mice. The dephosphorylation signal to eliminate phosphate was crucial, and these results unveiled the mechanism and biological relevance of the dephosphorylation of Prm2 for sperm maturation in vivo.