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Takashi Miyachi,1 Kyoko Nomura,2 Sachiko Minamizono,2 Kazuki Sakai,1 Toyoto Iwata,2 Yuta Sugano,1 Shun Sawaguchi,3 Kouhei Takahashi,3 Kazuo Mishima4 1Department of Medicine, Akita University Graduate School of Medicine, Akita, Japan; 2Department of Environmental Health Science and Public Health, Akita University Graduate School of Medicine, Akita, Japan; 3Japan Health Insurance Association, Akita Branch, Akita, Japan; 4Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, JapanCorrespondence: Kyoko NomuraDepartment of Environmental Health Science and Public Health, Akita University Graduate School of Medicine, 1– 1– 1 Hondo, Akita, 010-8543, JapanTel +81-18-884-6086Fax +81-18-836-2609Email nomurakyoko@gmail.comPurpose: Truck drivers with insomnia are at a high risk of traffic accidents. We aimed to investigate the prevalence of insomnia and identify its associated factors among truck drivers in Japan.Methods: Participants were 2927 male truck drivers younger than 65 years old. Self-administered questionnaires were used to assess insomnia symptoms, State-Trait Anxiety Inventory, drinking, smoking habits, body mass index, caffeine intake, as well as daily driving hours, consecutive days away from home, and driving distance. Insomnia symptoms included difficulty initiating sleep, maintaining sleep and early morning awakening. Insomnia was defined when any of these symptoms were observed with daily tiredness.Results: The prevalence of insomnia among the subjects was 13.3% (n=356), of which 13.5% had difficulty initiating sleep, 78% had difficulty maintaining sleep, and 26.4% had early morning awakening. After adjusting for covariates, drinking habits, daily driving hours, and STAI score were significantly and linearly associated with insomnia; the adjusted odds ratio (OR) of drinking habits for insomnia was 1.74 [95% confidence interval (CI), 1.23– 2.47] for heavy drinkers compared to non-drinkers (trend p< 0.001); the adjusted OR of daily driving hours was 1.87 (95% CI, 1.00– 3.49) for 12 hours or longer in a day compared to < 8 hours in a day (trend p< 0.001); the adjusted OR of STAI quartiles was 5.30 (95% CI, 3.66– 7.67) for the highest quartile compared to the lowest quartile (trend p< 0.001).Conclusion: The present study demonstrated that insomnia is prevalent among truck drivers in Japan, and its risk factors include drinking habits, daily driving hours, and anxiety.Keywords: insomnia, truck driver, State-Trait Anxiety Inventory, STAI, working environment, lifestyle

Abstract To elucidate the molecular mechanisms underling hydration during oocyte maturation, we characterized the structure of Japanese eel (Anguilla japonica) novel-water selective aquaporin 1 (AQP1b) that thought to be involved in oocyte hydration. The aqp1b cDNA encodes a 263 amino acid protein that includes the six potential transmembrane domains and two Asn-Pro-Ala motifs. Reverse transcription-polymerase chain reaction showed transcription of Japanese eel aqp1b in ovary and testis but not in the other tissues. In situ hybridization studies with the eel aqp1b cRNA probe revealed intense eel aqp1b signal in the oocytes at the perinucleolus stage and the signals became faint during the process of oocyte development. Light microscopic immunocytochemical analysis of ovary revealed that the Japanese eel AQP1b was expressed in the cytoplasm around the yolk globules which were located in the peripheral region of oocytes during the primary yolk globule stage; thereafter, the immunoreactivity was observed throughout the cytoplasm of oocyte as vitellogenesis progressed. The immunoreactivity became localized around the large membrane-limited yolk masses which were formed by the fusion of yolk globules during the oocyte maturation phase. These results together indicate that AQP1b, which is synthesized in the oocyte during the process of oocyte growth, is essential for mediating water uptake into eel oocytes.

Transmembrane protein 106B (TMEM106B), which is a type II transmembrane protein, is believed to be involved in intracellular dynamics and morphogenesis in the lysosome. TMEM106B is known to be a risk factor for frontotemporal lobar degeneration and has been recently identified as the receptor needed for the entry of SARS-CoV-2, independently of angiotensin-converting enzyme 2 (ACE2). A missense mutation, p.Asp252Asn, of TMEM106B is associated with hypomyelinating leukodystrophy 16 (HLD16), which is an oligodendroglial cell-related white matter disorder causing thin myelin sheaths or myelin deficiency in the central nervous system (CNS). However, it remains to be elucidated how the mutated TMEM106B affects oligodendroglial cells. Here, we show that the TMEM106B mutant protein fails to exhibit lysosome distribution in the FBD-102b cell line, an oligodendroglial precursor cell line undergoing differentiation. In contrast, wild-type TMEM106B was indeed localized in the lysosome. Cells harboring wild-type TMEM106B differentiated into ones with widespread membranes, whereas cells harboring mutated TMEM106B failed to differentiate. It is of note that the output of signaling through the lysosome-resident mechanistic target of rapamycin (mTOR) was greatly decreased in cells harboring mutated TMEM106B. Furthermore, treatment with hesperetin, a citrus flavonoid known as an activator of mTOR signaling, restored the molecular and cellular phenotypes induced by the TMEM106B mutant protein. These findings suggest the potential pathological mechanisms underlying HLD16 and their amelioration.

Purpose: To evaluate the changes in choroidal thickness 1 year after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) using widefield swept-source optical coherence tomography., Methods: We retrospectively reviewed 21 patients with CSC who unilaterally underwent half-dose PDT and completed a 12-month follow-up. Choroidal thickness was evaluated before and after PDT within an 18-mm circular grid centered on the fovea subdivided into nine areas in the treated and untreated fellow eyes., Results: All 21 treated eyes showed complete resolution of subretinal fluid at 3 months after PDT, without any recurrence at 12 months. The mean choroidal thickness in all nine areas significantly decreased after PDT at 3 months (P < 0.05) and remained unchanged at 12 months (P < 0.05) compared with that at baseline. However, the subtracted choroidal thickness maps between 3 and 12 months detected significant variations among the cases, classified into an enhanced pattern in 10 eyes (47.6%), an attenuated pattern in six eyes (28.6%), and a stable pattern in five eyes (23.8%). The 21 untreated fellow eyes also showed a decrease in mean choroidal thickness in three of the nine subdivided areas at 12 months (P < 0.05), but this decrease was limited posteriorly., Conclusion: The reduction in mean choroidal thickness after half-dose PDT for CSC was extensively maintained for 1 year. However, subclinical hemodynamic changes in the entire choroid occurred longitudinally even in the absence of disease recurrence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the association between scleral thickness and a newly developed multimodal imaging-based classification of central serous chorioretinopathy (CSC)., Design: Retrospective, cross-sectional study., Methods: This study included 217 eyes of 217 patients classified as simple or complex CSC based on the established protocols. Clinical and anatomical factors were compared between the 2 types. The scleral thickness was measured at 4 locations using anterior-segment optical coherence tomography., Results: Of the 217 eyes, 167 were classified as simple CSC and 50 as complex CSC. The complex CSC group showed older age (P = .011), higher male ratio (P = .001), more bilateral involvement (P < .001), poorer visual acuity (P < .001), greater subfoveal choroidal thickness (P = .025), and higher frequency of loculation of fluid (P < .001) and ciliochoroidal effusion (P < .001) than the simple CSC group. The complex CSC group had significantly greater scleral thicknesses in the superior, temporal, inferior, and nasal directions (all P < .001) than the simple CSC group. Multivariable analysis revealed that older age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.013-1.097, P < .001), male sex (OR 10.445, 95% CI 1.151-94.778, P < .001), bilateral involvement (OR 7.641, 95% CI 3.316-17.607, P < .001), and the mean value of scleral thicknesses in 4 directions (OR 1.022, 95% CI 1.012-1.032, P < .001) were significantly associated with the complex CSC., Conclusions: Older age, male sex, bilateral involvement, and thick sclera were associated with the complex CSC. Scleral thickness seemed to determine the clinical manifestations of CSC., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: There are few reports on bowel preparation for early colonoscopy in patients with suspected colonic diverticular bleeding (CDB). We aim to clarify in a retrospective, multicenter study., Methods: In a multicenter retrospective cohort study at 10 institutions, we analyzed clinical features of patients diagnosed with CDB, who underwent early colonoscopy within 24 h. We compared patients who were prepared with polyethylene glycol lavage (PEL) and those without PEL. We evaluated the effects of PEL for early colonoscopy in patients with suspected CDB., Results: A total of 129 (53%) underwent under preparation with PEL and 113 patients without PEL. The PEL group was younger, had fewer comorbidities, and had better performance status. After adjusting for these variables with propensity score matching, the PEL group had a significantly shorter hospital stay (7.9 ± 4.7 vs. 10.1 ± 5.2 days; p  = 0.001), and a higher cecal intubation rate (91.1% vs. 50.0%; p  < 0.001). There were no significant differences in adverse event rates, identification of stigmata of recent hemorrhage, or frequency in endoscopic hemostatic treatment., Conclusions: PEL may be preferred for early colonoscopy in patients suspected of having CDB., Competing Interests: Authors declare no conflicts of interest for this article. Author Takayuki Matsumoto is an advisory member of DEN Open., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Purpose: The sclera is reportedly thicker in eyes with central serous chorioretinopathy (CSC) than in healthy control eyes. We compared the scleral thicknesses of the affected and unaffected fellow eyes of patients with unilateral CSC., Methods: We retrospectively examined the findings of 115 patients with unilateral CSC. Comparisons of the spherical equivalent, axial length, anterior chamber depth, subfoveal choroidal thickness, scleral thickness, and presence of peripheral ciliochoroidal effusion of the affected and fellow eyes were made. Using anterior segment optical coherence tomography, scleral thickness was measured vertically, 6 mm posterior to the scleral spur in the superior, temporal, inferior, and nasal directions., Results: No significant differences in scleral thickness in all four directions, spherical equivalent, axial length, anterior chamber depth, and frequency of ciliochoroidal effusion were found between the affected and unaffected fellow eyes. The only significant difference between the affected and fellow eyes was observed in the subfoveal choroidal thickness (398.8 µ m vs. 346.6 µ m, P < 0.001)., Conclusion: A thickened choroid seems to have a direct effect on CSC development. By contrast, the affected and fellow eyes showed no significant difference in scleral thickness, indicating that scleral thickening may be a predisposing factor for the development of CSC.

Purpose: Central serous chorioretinopathy (CSC) is a retinal disorder characterized by serous retinal detachment with or without pigment epithelial detachment in the posterior pole of the eye. We aimed to elucidate the relationship between scleral thickness and choroidal structure in CSC eyes., Methods: This single-center retrospective study included 111 eyes of 111 CSC patients. Using swept-source optical coherence tomography, the horizontal cross-sectional images of the posterior choroid were converted to binary images by semiautomated software. The luminal and stromal areas of the choroid were measured, and the luminal/stromal (L/S) ratios of the whole choroid (WC), inner choroid, and outer choroid (OC) at 1500 µm, 3000 µm, and 7500 µm ranges centered on the fovea were calculated. Correlations of L/S ratio and age, spherical equivalent, axial length, subfoveal choroidal thickness (SCT), and scleral thickness were determined. Scleral thickness was measured vertically, 6 mm posterior to the scleral spur in four directions., Results: SCT and mean scleral thickness were significantly positively correlated with the L/S ratio in all ranges of WC and OC. Multiple regression analysis found that SCT and mean scleral thickness were significantly correlated with the L/S ratio, and the strength of correlation of mean scleral thickness (WC: 0.386, P < 0.001; OC: 0.391, P < 0.001) was greater than that of SCT (WC: 0.368, P < 0.001; OC: 0.383, P < 0.001) in 7500 µm range., Conclusions: Thick sclera appeared to play a role in an increase in the luminal component of the posterior choroid in CSC eyes.

Hypomyelinating leukodystrophy 10 (HLD10) is an autosomal recessive disease related to myelin sheaths in the central nervous system (CNS). In the CNS, myelin sheaths are derived from differentiated plasma membranes of oligodendrocytes (oligodendroglial cells) and surround neuronal axons to achieve neuronal functions. Nucleotide mutations of the pyrroline-5-carboxylate reductase 2 (PYCR2) gene are associated with HLD10, likely due to PYCR2's loss-of-function. PYCR2 is a mitochondrial residential protein and catalyzes pyrroline-5-carboxylate to an amino acid proline. Here, we describe how each of the HLD10-associated missense mutations, Arg119-to-Cys [R119C] and Arg251-to-Cys [R251C], lead to forming large size mitochondria in the FBD-102b cell line, which is used as an oligodendroglial cell differentiation model. In contrast, the wild type proteins did not participate in the formation of large size mitochondria. Expression of each of the mutated R119C and R251C proteins in cells increased the fusion abilities in mitochondria and decreased their fission abilities relatively. The respective mutant proteins, but not wild type proteins also decreased the activities of mitochondria. While cells expressing the wild type proteins exhibited differentiated phenotypes with widespread membranes and increased expression levels of differentiation marker proteins following the induction of differentiation, cells harboring each of the mutant proteins did not. Taken together, these results indicate that an HLD10-associated PYCR2 mutation leads to the formation of large mitochondria with decreased activities, inhibiting oligodendroglial cell morphological differentiation. These results may reveal some of the pathological mechanisms in oligodendroglial cells underlying HLD10 at the molecular and cellular levels.

Hypomyelinating leukodystrophy 17 is an autosomal recessive disease affecting myelin-forming oligodendroglial cells in the central nervous system. The gene responsible for HLD17 encodes aminoacyl-tRNA synthase complex-interacting multifunctional protein 2, whose product proteins form a scaffold that supports aminoacyl-tRNA synthetases throughout the cell body. Here we show that the HLD17-associated nonsense mutation (Tyr35-to-Ter [Y35X]) of AIMP2 localizes AIMP2 proteins as aggregates into the Golgi bodies in mouse oligodendroglial FBD-102b cells. Wild type AIMP2 proteins, in contrast, are distributed throughout the cell body. Expression of the Y35X mutant proteins, but not the wild type proteins, in cells upregulates Golgi stress signaling involving caspase-2 activation. Cells expressing the wild type proteins exhibit differentiated phenotypes with web-like structures bearing many processes following the induction of differentiation, whereas cells expressing the Y35X mutant proteins fail to differentiate. Furthermore, CASP2 knockdown but not control knockdown reverses the phenotypes of cells expressing the mutant proteins. These results suggest that HLD17-associated AIMP2 mutant proteins are localized in the Golgi bodies where their proteins stimulate Golgi stress-responsive CASP2 to inhibit differentiation; this effect is ameliorated by knockdown of CASP2. These findings may reveal some of the molecular and cellular pathological mechanisms underlying HLD17 and possible approaches to ameliorating the disease's effects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hereditary peripheral neuropathies called Charcot-Marie-Tooth (CMT) disease affect the sensory nerves as well as motor neurons. CMT diseases are composed of a heterogeneous group of diseases. They are characterized by symptoms such as muscle weakness and wasting. Type 2 CMT (CMT2) disease is a neuropathy with blunted or disrupted neuronal morphological differentiation phenotypes including process formation of peripheral neuronal axons. In the early stages of CMT2, demyelination that occurs in Schwann cells (glial cells) is rarely observed. CMT2W is an autosomal-dominant disease and is responsible for the gene encoding histidyl-tRNA synthetase 1 (HARS1), which is a family molecule of cytoplasmic aminoacyl-tRNA synthetases and functions by ligating histidine to its cognate tRNA. Despite increasing knowledge of the relationship of mutations on responsible genes with diseases, it still remains unclear how each mutation affects neuronal differentiation. Here we show that in neuronal N1E-115 cells, a severe Asp364-to-Tyr (D364Y) mutation of HARS1 leads to formation of small aggregates of HARS1 proteins; in contrast, wild type proteins are distributed throughout cell bodies. Expression of D364Y mutant proteins inhibited process formation whereas expression of wild type proteins possessed the normal differentiation ability to grow processes. Pretreatment with the antiepileptic valproic acid recovered inhibition of process formation by D364Y mutant proteins through the c-Jun N-terminal kinase signaling pathway. Taken together, these results indicate that the D364Y mutation of HARS1 causes HARS1 proteins to form small aggregates, inhibiting process growth, and that these effects are recovered by valproic acid. This could be a potential therapeutic drug for CMT2W at the cellular levels., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)