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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

Objective: In preterm and very low birth weight (VLBW) infants, attention-related problems have been found to be more pronounced and emerge later as academic difficulties that may persist into school age. In response, based on three attention networks: alerting, orienting, and executive attention, we examined the development of attention functions at 42 months (not corrected for prematurity) as a follow-up study of VLBW ( n  = 23) and normal birth weight (NBW: n  = 48) infants., Method: The alerting and orienting attention networks were examined through an overlap task with or without warning signal. The orienting network was also examined through the distribution of gaze points when exposed to videos of human faces talking and silently looking straight ahead. Executive attention was examined using a parental report measure for temperamental self-regulation, effortful control., Results: In the overlap task, the difference between VLBWs and NBWs was not the latency of attentional disengagement but the fact that VLBWs were less focused on the fixation stimulus ( F (1,60) = 10.80, p  < .01, η p 2  = .071) and seemed to profit more from auditory warning signals than NBWs ( F (1,60) = 7.13, p  = .01, η p 2  = .106). Moreover, there was no intergroup difference regarding lateral (right or left) or feature (eye or mouth) attention bias toward the face videos. Further, longer latencies in overlap condition were significantly positively associated with high effortful control scores only in the NBW group ( r  = .36, p  = .018)., Conclusion: Results indicate that poor underlying alertness and orienting relating to atypical lateralization may affect cognitive and behavioral abnormalities in VLBWs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dynamic WaveArc (DWA) is a technique used for continuous, non-coplanar volumetric-modulated arc therapy on the Vero4DRT platform. This study aimed to evaluate the application of single-isocenter DWA (SI-DWA) for treating multiple brain metastases by comparing dose distribution and irradiation time with multi-isocenter DWA (MI-DWA) through retrospective treatment planning. Treatment plans were developed for SI-DWA and MI-DWA in 14 cases with 3-5 brain metastases. Parameters assessed included target dose indices, such as conformity index (CI) of the planning target volume (PTV), volumes of normal brain excluding gross tumor volumes (GTVs) receiving a single dose equivalent of 14 Gy (V14), V30%, V20%, V10%, volumes of normal brain, including GTVs receiving a single dose equivalent of 12 Gy (V12), D2% for other organs at risk, and beam-on time. SI-DWA showed inferior CI, V14, and V12 values for lesions with PTV volumes <1 cc, whereas it performed equivalently to MI-DWA for lesions with PTV volumes ≥1 cc. SI-DWA resulted in higher volumes of normal brain receiving low doses compared to MI-DWA. SI-DWA exhibited significantly shorter beam-on times than MI-DWA. In conclusion, SI-DWA is an effective method for treating multiple brain metastases with PTV volumes ≥1 cc, offering an index of radiation-induced brain necrosis comparable with MI-DWA while allowing for shorter irradiation times., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: Heterotopic ossification (HO) can occur after hemiarthroplasty (HA) for femoral neck fractures (FNF). This study aimed to investigate the frequency and factors contributing to the development of HO after HA., Methods: The study included data from 92 of 183 patients (26 male and 66 female) who sustained FNF and underwent HA between April 2019 and January 2022. HO was identified on postoperative radiographic images. Patient background, operative duration, blood loss, and presence of free bone fragments immediately after surgery were compared between the HO and non-HO groups. Statistical analyses included the independent-sample t-test for continuous variables and the chi-squared test for categorical variables. A multivariate logistic regression analysis was performed using HO as an objective variable., Results: HO occurred in 50 of the 92 (54%) patients. There were no statistically significant differences in patient backgrounds. Univariate analysis revealed significantly longer mean operative duration and greater blood loss in the HO group. Free bone fragments in the immediate postoperative period were observed in 29 of 50 (58%) patients in the HO group and in 3 of 42 (7.1%) patients in the non-HO group, a statistically significant difference. Logistic regression analysis revealed that the presence of free bone fragments was an independent explanatory factor for HO development., Conclusion: The presence of free bone fragments immediately after surgery may be significantly associated with the development of HO. Therefore, it is necessary to sufficiently remove such fragments during surgery because they may trigger HO., (© 2024. The Author(s).)

Background: Since the 1920s, motor development has been a strong research theme, focusing on infants' acquisition of motor skills, such as turning over and crawling. In the 1980s, a dynamic systems approach began emphasizing children's own motivation, which helped explain individual differences in the emergence of motor skills. However, few studies have examined factors contributing to individual differences in early motor development. In response, we investigated directional associations between temperament and motor development in children aged 6 months to 3 years., Method: The Japan Environment and Children's Study (JECS-A) recruited mothers between January 2011 and March 2014. 2,639 mothers were sent a questionnaire at 6 months, and responses were received from 1,657 of them, with full data for children aged 6 months, 2 years, and 3 years, including from three mothers of twins, were analyzed through structural equation modeling. Question items regarding fine and gross motor activities at each age were selected by pediatric neurologists specializing in developmental disorders. The Japanese version of the Little Developmental Coordination Disorder Questionnaire was administered at 42 months. Temperament was assessed through the parent-reported Behavior Questionnaire (short version) for infants, toddlers, and children. In all three measures, Surgency and Negative Affectivity were extracted, and Effortful Control, a major form of self-regulation, was found from toddlerhood onward, as in previous studies., Results: A path diagram reveals that at 6 months, Surgency and Orienting/Regulation interacted positively with the motor function (respectively, r = .57; r = 40, ps < .001). Up to about 3 years, Effortful Control plays a role in facilitating the motor function, resulting in positive effects on Control During Movement (CDM), General Coordination (GC), and Fine Motor Movement (FMM) (β = 14; β = 30; β = 37, ps < .001). Surgency had a positive effect on CDM and GC (β = 18; β = 06, ps < .001), whereas Negative Affect had a negative influence on FMM and GC (β = -.08; β = -.08, ps < .001)., Conclusion: While Surgency may be a key reactive factor in early motor development, Effortful Control and Movement develop in an interactive manner., Trial Registration: UMIN000030786. Scientific Title: The Japan Environment and Children's Study. Date of disclosure of the study: 2018/01/15. Only questionnaires were administered in the study., (© 2024. The Author(s).)

Background and Aims: In the neurobiological theory of attention, the orienting network mainly supports the temperamental regulatory function in infancy, with soothing methods such as visual attention distraction influencing its development. The attention distraction method chosen for soothing is thought to be influenced by maternal sensitivity, which has been found to decrease with poor maternal mental health. We hypothesize that the degree of maternal distress may affect the choice of attention distraction soothing method. Further, individual differences in being soothed by attention distraction will be associated with the temperamental regulation function in infancy/toddlerhood., Method: Structural equation modeling (SEM) was conducted on longitudinal data at 6 and 24 months on a sample ( N  = 1892) drawn from the sub-cohort of the Japan Environment and Children's Study (JECS). Temperament was examined through the short Infant Behavior Questionnaire-Revised (Japanese version) and the Early Childhood Behavior Questionnaire (Japanese version). Distress in caregivers was measured through the Kessler Psychological Distress Scale (Japanese version) at prenatal and 1-year-postnatal stages. Individual differences in using visual distraction soothing methods were also measured using tailor-made items., Results: Postnatal maternal distress at 12 months was negatively related to the tendency to use visual attention distraction as a soothing method (β = -0.06, p  = 0.006) at 24 months. When we applied the subscale of the temperamental regulatory factor in SEM, the more the mothers chose the distraction method for soothing, i.e., the more the toddlers experienced it, the higher their attention shifting scores (β = 0.07, p  = 0.002)., Conclusion: The findings support the view that caregivers' choice of method for distracting offspring's attention from distress may be associated with the development of self-regulation during infancy and toddlerhood., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Proton (H + ) release is linked to aluminum (Al)-enhanced organic acids (OAs) excretion from the roots under Al rhizotoxicity in plants. It is well-reported that the Al-enhanced organic acid excretion mechanism is regulated by SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1), a zinc-finger TF that regulates major Al tolerance genes. However, the mechanism of H + release linked to OAs excretion under Al stress has not been fully elucidated. Recent physiological and molecular-genetic studies have implicated the involvement of SMALL AUXIN UP RNAs (SAURs) in the activation of plasma membrane H + -ATPases for stress responses in plants. We hypothesized that STOP1 is involved in the regulation of Al-responsive SAURs , which may contribute to the co-secretion of protons and malate under Al stress conditions. In our transcriptome analysis of the roots of the stop1 (sensitive to proton rhizotoxicity1) mutant, we found that STOP1 regulates the transcription of one of the SAURs , namely SAUR55 . Furthermore, we observed that the expression of SAUR55 was induced by Al and repressed in the STOP1 T-DNA insertion knockout (KO) mutant ( STOP1 -KO). Through in silico analysis, we identified a functional STOP1-binding site in the promoter of SAUR55 . Subsequent in vitro and in vivo studies confirmed that STOP1 directly binds to the promoter of SAUR55 . This suggests that STOP1 directly regulates the expression of SAUR55 under Al stress. We next examined proton release in the rhizosphere and malate excretion in the T-DNA insertion KO mutant of SAUR55 ( saur55 ), in conjunction with STOP1 -KO. Both saur55 and STOP1 -KO suppressed rhizosphere acidification and malate release under Al stress. Additionally, the root growth of saur55 was sensitive to Al-containing media. In contrast, the overexpressed line of SAUR55 enhanced rhizosphere acidification and malate release, leading to increased Al tolerance. These associations with Al tolerance were also observed in natural variations of Arabidopsis. These findings demonstrate that transcriptional regulation of SAUR55 by STOP1 positively regulates H + excretion via PM H + -ATPase 2 which enhances Al tolerance by malate secretion from the roots of Arabidopsis. The activation of PM H + -ATPase 2 by SAUR55 was suggested to be due to PP2C.D2/D5 inhibition by interaction on the plasma membrane with its phosphatase. Furthermore, RNAi-suppression of NtSTOP1 in tobacco shows suppression of rhizosphere acidification under Al stress, which was associated with the suppression of SAUR55 orthologs, which are inducible by Al in tobacco. It suggests that transcriptional regulation of Al-inducible SAUR s by STOP1 plays a critical role in OAs excretion in several plant species as an Al tolerance mechanism., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Previously, insomnia and adverse lifestyle were prevalent among truck drivers, but the association between the two remains unknown in this particular occupational cohort. This study aimed to examine the relationship between insomnia and lifestyle-related diseases among truck drivers. We investigated 875 male truck drivers of the Japan Truck Association, Akita branch, as of July 2020. The definition of insomnia was based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Data from a self-administered questionnaire were merged with health records and health insurance claims data of 2020. In total, 40.1% had either one of the lifestyle-related diseases including hypertension (29.7%), diabetes mellitus (11.7%), and dyslipidemia (24.8%), whereas according to ICSD-3, 13.2% had insomnia. Multivariate logistic regression models demonstrated that individuals with insomnia had approximately 2-fold increased risk of having at least one lifestyle-related disease (p < 0.001), hypertension (p = 0.0027), diabetes mellitus (p = 0.0654) and dyslipidemia (p < 0.001). Occupational characteristics including daily driving hours, driving distance, and travel days were not associated with any lifestyle-related diseases except for an association between short-haul and at least one disease. In conclusion, insomnia is significantly associated with increased risks of lifestyle-related diseases among male truck drivers in Japan.

Aim: To investigate whether rightward attention to the mouth during audiovisual speech perception may be a behavioural marker for early brain development, we studied very preterm and low birthweight (VLBW) and typically developing (TD) toddlers., Methods: We tested the distribution of gaze points in Japanese-learning TD and VLBW toddlers when exposed to talking, silent and mouth moving faces at 12, 18 and 24 months (corrected age). Each participant was categorised based upon the area they gazed at most (Eye-Right, Eye-Left, Mouth-Right, Mouth-Left) per stimulus per age. A log-linear model was applied to three-dimensional contingency tables (region, side and group)., Results: VLBW toddlers showed fewer gaze points than TD toddlers. At 12 months, more VLBW toddlers than TD toddlers showed left attentional bias toward any one face; however, this difference in attention asymmetry receded somewhat by 24 months. In talking condition, TD toddlers showed right attentional bias from 12 to 24 months, whereas VLBW toddlers showed such bias upon reaching 24 months. Additionally, more TD toddlers than VLBW toddlers attended to the mouth., Conclusion: Delays in exhibiting the attentional bias for an audiovisual face or general faces displayed by typically developing children might suggest differential developmental timing for hemispheric specialisation or dominance., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12 months or older., Methods: Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24 months. Crawling was rated by mothers at 12 months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire., Results: At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12 months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months., Conclusion: Short fragmental sleep in early infancy did not always predict poor development., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

This study investigated the intention to get the coronavirus disease of 2019 (COVID-19) vaccine and its associated factors among Japanese university students. A cross-sectional survey was conducted from March to May 2021 via an e-learning platform at Akita University. Participants were 1776 graduate and undergraduate students who answered the survey on vaccine intention, the health belief model (HBM), sociodemographic characteristics, and concerns over COVID-19-related situations. Vaccine intention was stratified into active, slightly less, and no intention, and the associated factors were determined using the multinomial logistic regression model. Results showed that 56.7% of students had active intention, followed by slightly less intention (34.5%) and no intention (8.8%). After adjusting for covariates, healthcare course, perceived severity (life-threatening and serious social consequences), and perceived benefits from HBM were significantly associated with active intention, with adjusted odds ratios of 4.02 (95% confidence interval [CI], 2.11-7.67), 1.40 (95% CI, 1.16-1.69), 1.23 (95% CI, 1.04-1.46), and 2.03 (95% CI, 1.66-2.49), respectively; perceived barriers (side effect, troublesome, and parent disagreement) were adversely associated with active intention. The public health strategy to improve students' vaccine uptake requires providing accurate information on vaccine safety and efficacy while removing any barriers to vaccination.

In March 2020, many schools were closed to prevent the spread of COVID-19 in Japan, and it is predicted that many children, especially those with neurodevelopmental disorders (NDDs), will be affected emotionally and behaviorally. Here, we examined the impact of school closures due to COVID-19 on school-aged children with NDDs using the Child Behavior Checklist. Totally, data on 121 children diagnosed with autism spectrum disorder, attention-deficit hyperactivity disorder, and/or intellectual disorder were analyzed and it was found that externalizing and aggressive behavior increased in all NDDs, regardless of the type of diagnosis. A clear prospect is important for children with NDDs children to lead a stable life, and more generous supports for children with NDDs and their families are needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The detrimental impacts of abuse on victims' well-being are well documented globally, including Japan. The ongoing COVID-19 pandemic may increase the incidence of abuse in the community, creating an additional burden amid the crisis. However, the incidence of abuse in Japan during COVID-19 remains to be evaluated. Accordingly, our study aimed to assess the incidence of physical and verbal abuse among the general population in Japan and to identify the associated factors of abuse during COVID-19., Design and Setting: We used the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were used to calculate national estimates, and multivariable logistic regression was performed to identify the associated factors for physical and verbal abuse., Results: Out of the total 25 482 participants, 965 (3.8 %) reported experiencing physical abuse and 1941 (7.6%) verbal abuse from April 2020 to September 2020. The incidence of physical and verbal abuse was higher among female participants. Participants who lived in areas where the 'state of emergency' was enforced were more likely to suffer from physical abuse. Similarly, vulnerable participants such as those below age 18, with low income, bad family relationships, and disabled people were more likely to experience both physical and verbal abuse. Participants suffering from COVID-19-related symptoms, who had poor health status and widows/divorcees were more likely to be verbally abused. Furthermore, those who did not follow preventive behaviours such as wearing masks in public places, abusing drugs and drinking alcohol in high amounts were also more likely to experience abuse., Conclusion: The impact of abuse was found disproportionately greater in more vulnerable groups of the population. Pandemic has reinforced the existing social inequalities, which need to be addressed timely to prevent precarious repercussions., Competing Interests: Competing interests: AO received personal fees from MNES, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective/background: Insomnia among truck drivers may contribute to traffic accidents. We previously reported that truck drivers had adverse lifestyle habits, including smoking and drinking alcohol, in addition to enforced sedentarism making them more vulnerable to lifestyle-related diseases. This study aimed to investigate the association between insomnia and diabetes, as well as the effect of anxiety related to driving tasks on this association., Patients/methods: A total of 755 male truck drivers under 65 years of age who belonged to Akita prefecture Truck Association in Japan were investigated. Insomnia and State-Trait Anxiety Inventory (STAI) score were assessed using a self-administered questionnaire in 2020. Insomnia was defined in accordance with International classification of sleep disorders-third edition. Diabetes was defined as a fasting blood glucose level of ≥126 mg/dL and/or use of anti-diabetic drugs using data obtained from health checkups in 2018., Results: The proportions of truck drivers with insomnia and diabetes were 13.9% and 9.7%, respectively, which were higher than those in the general working population in Japan. After adjusting for age, smoking, drinking, daily hours of driving and sleep, and hypertension, the STAI score (odds ratio [OR] for the highest quartile vs. the lowest: 3.88, 95% confidence interval [CI]: 1.84-8.18) and diabetes (OR: 2.49, 95% CI: 1.11-5.60) were found to be associated with insomnia. A statistical interaction with STAI scores was not observed between diabetes and insomnia., Conclusions: The present study demonstrated that diabetes and anxiety are independently and significantly associated with insomnia in male Japanese truck drivers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Dr. Ozaki received personal fees from Medical Network Systems outside the scope of the submitted work; Dr. Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd. outside the scope of the submitted work.

Although genetic factors are involved in the etiology of autism spectrum disorder (ASD), the significance of genetic analysis in clinical settings is unclear. Forty-nine subjects diagnosed with non-syndromic ASD were analyzed by microarray comparative genomic hybridization (CGH) analysis, whole-exome sequencing (WES) analysis, and panel sequencing analysis for 52 common causative genes of ASD to detect inherited rare variants. Genetic analysis by microarray CGH and WES analyses showed conclusive results in about 10% of patients, however, many inherited variants detected by panel sequencing analysis were difficult to interpret and apply in clinical practice in the majority of patients. Further improvement of interpretation of many variants detected would be necessary for combined genetic tests to be used in clinical settings., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is often used to treat patients with neurological impairment and difficulty in swallowing. However, these patients often develop copper deficiency. This report describes a case of isolated neutropenia, which is a rare manifestation of copper deficiency., Case Summary: Our patient was a 19-year-old boy with neurological impairment and gastroesophageal reflux. He received PEG-J feeding, including an enteral supplement containing copper and zinc. However, as his serum zinc level was low (53 μg/dL) at the age of 19 years and 2 mo, we changed to a zinc-rich supplement containing 22 mg/d of zinc and 1.0 mg/d of copper. The supplement comprised a mixture of isocal 1.0 junior (5 packs/d), Tezon [2 packs (250 mL)/d], and cocoa powder. Seven months later, he had neutropenia (606/mm 3 ) with a serum copper level of 16 μg/dL. There were no other manifestations of copper deficiency, including anemia. Copper deficiency and neutropenia both improved following the administration of cocoa powder and Tezon., Conclusion: In patients receiving long-term PEG-J feeds, white blood cell counts, hemoglobin, and serum levels of copper and zinc should be regularly monitored., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

In Japan, the production of Leuplin ® , a key drug for the treatment of prostate cancer and breast cancer, was temporarily suspended in 2020 by the manufacturer. The incident illustrated several significant failings, namely the lack of uniformity in international GMP (Good Manufacturing Practice) regulations, the lack of mechanisms to resolve disputes between PIC/S (Pharmaceutical Inspection Co-operation Scheme) member countries, and the importance of maintaining a stable supply of safe GMP-compliant essential medicines., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

The 'Opioid Crisis', which originated in Western countries, has been misrepresented and is misinforming the global public. For 20 years, since the advent of the synthetic opioids, 25,000 Americans, on average, have died annually from opioid-related overdoses. The United States produces and consumes by far the greatest amounts of opioids. National regulations introduced to curb overdoses and restrict opioid availability have condemned many Americans, such as cancer patients or those in need of palliative care, to a life of extreme pain due to lack of access to adequate pain management. As is often the case, US-driven laws have informed and guided international regulations. Worldwide, 83% of countries have low or non-existent access to opioids for pain relief. Over 25 million people are at the end-of-life stage, with eight million people dying annually in unnecessary pain and distress. Ineffectively controlled pain is a global public health issue blighting the lives of billions of people worldwide with immeasurable human and socioeconomic costs. International conventions regulate the trade and use of controlled medications, including many opioids. The goal is to balance widespread access to optimal forms of pain management with restrictions to govern the use and prevent the misuse of controlled substances. Those conventions are failing to meet their goals. International guidelines to inform national legislation have been compromised and withdrawn, thanks to undue interference from US-based opioid manufacturers. The new goal must be to ensure equitable access, for all, to opioids and ensure that optimal pain management becomes a central component of Universal Health Coverage. SIGNIFICANCE: The opioid crisis is, more accurately, a multicomponent global crisis and one that is not fully apparent or well understood. Regulations of the wealthy and powerful to control a surfeit of opioids, which encourages misuse, cannot be allowed to govern legislation in the majority of countries worldwide where citizens have little or no access to opioids to reduce pain and suffering. International conventions must be revised to ensure an optimal balance that allows access to opioids for all those who need them., (© 2021 European Pain Federation - EFIC®.)

A questionnaire survey was conducted on 8,402 members of the Japanese Neurological Society to examine the current status and countermeasures for physician burnout, and 1,261 respondents (15.0%) responded. In this paper, we report the results of a comparison between male and female physicians. There was a significant difference in working and living conditions only for married people. It was confirmed that men work under stricter conditions in terms of working hours, and that the burden on women is heavier in the division of housework. Analysis using the Japanese Burnout Scale revealed no gender differences in overall scores, but as for factors related to burnout, in addition to factors common to both men and women, factors specific to men or women were clarified.

To identify factors associated with burnout among Japanese physician and to use them in future measures, the Japanese Society of Neurology conducted a survey of neurologists on burnout using a web-based questionnaire in October 2019. A total of 1,261 respondents, 15.0% of the 8,402 members, responded to the survey. The mean of the subscales of the Japanese Burnout Scale was 2.86/5 points for emotional exhaustion, 2.21/5 points for depersonalization, and 3.17/5 points for lack of personal accomplishment. In addition, the burnout of our country's neurologists is not related to workloads such as working hours and the number of patients in charge, but also to a decreased meaningfulness and professional accomplishment. Therefore, it is necessary to take comprehensive measures to improve these issues at the individual, hospital, academic and national levels.

Background: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation., Methods: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses., Findings: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children., Interpretation: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology., Funding: This study was supported mainly by MEXT, Japan., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A sex difference in the second-to-fourth digit ratio (2D:4D, males < females) has been described in Japanese fetuses and children, and its possible links to autism spectrum disorders (ASDs) have been discussed. Accordingly, this sexual difference in representative neonates merits examination., Aims: This study aimed to examine 2D:4D measurements and sexual differences in Japanese toddlers aged 1.5 years., Study Design and Subjects: The digit lengths used to calculate 2D:4D were measured using an easy-to-use photography method. A total of 1045 JECS-A (the Aichi regional sub-cohort of the Japan Environment and Children's Study) children (males, 523; females, 522) aged 1.5 years were analyzed., Results: The mean ages for the males and females were 575.3 ± 13.1 and 575.9 ± 17.1 days, respectively. Histograms of left and right 2D:4D were normally distributed regardless of sex (left male, 0.909 ± 0.048; left female, 0.913 ± 0.049, d = 0.08; right male, 0.938 ± 0.055; right female, 0.937 ± 0.049, d = 0.02). Because of high dispersion in the data, t-tests did not support a significant sex difference in 2D:4D. Post-hoc statistical power was calculated as 0.124 and the effect size for the sex difference in 2D:4D was 0.036., Conclusions: This study failed to confirm sexual differences in 2D:4D in 1.5-year-old Japanese children. This may be because digit measurement is difficult in this group, resulting in reduced effect sizes, or because rapid growth attenuates the in utero sexual dimorphism. This evidence is useful for the light it casts on the extreme male brain theory of ASDs., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health., Participants: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children., Findings to Date: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas., Future Plans: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a 77-year-old woman suffering from dementia with Lewy bodies (DLB) who presented with Hashimoto encephalopathy. The patient began to mistakenly believe that another person was sleeping in her bed from approximately 70 years of age. She began to show symptoms of parkinsonism after 75 years of age. One night, the patient began to exhibit loitering behavior, and made incomprehensible comments while also exhibiting other abnormal behaviors. Clinical examination revealed rigidity and tremor of the limbs, as well as hallucination, abnormal speech and behavior. We first considered DLB. However, serum anti-thyroglobulin levels turned out to be elevated, indicating Hashimoto encephalopathy as well, and treated the patient with steroid pulse therapy. Her mental symptoms subsequently improved, but rigidity and tremor remained. 123 I-ioflupane SPECT demonstrated decreased accumulation in the bilateral caudal basal ganglia. Anti NH 2 -terminal of α-enolase (NAE) antibody in the serum was positive. Therefore, we diagnosed the patient with the rare comorbidity of DLB and Hashimoto encephalopathy, successfully treated with immunotherapy.

Background: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects. We sought to investigate the effects and mechanisms of bariatric surgery on NASH improvement., Methods: Male Sprague-Dawley rats were fed by a high-fat and high-fructose diet, which results in obesity, insulin resistance, and NASH. Rats underwent duodenal-jejunal bypass (DJB), which is a main component of bariatric procedures. The liver pathological findings and the expression level of mRNA of FXR were investigated. The plasma BA level was measured in peripheral and portal vein blood., Results: DJB suppressed weight gain, improved insulin resistance, and ameliorated NASH mainly in a point of inflammation. The plasma BA level along with the expression of FXR and its target transcriptional factor, small heterodimer partner (SHP), in the liver were elevated., Conclusions: DJB has a direct effect on NASH improvement, and there is a possibility that an anti-inflammatory effect is functioning as a part of the mechanism. The increase of plasma bile acid level followed by the stimulation of FXR signaling may contribute to this phenomenon.

Background and Aims: Roux-en-Y gastric bypass improves glucose metabolism in clinical practice, and duodenal-jejunal bypass (DJB), an experimental bypass procedure, also improves metabolism in animals. However, the mechanism remains controversial; especially, the role of the biliopancreatic limb (BP-limb) remains unclear. Our aim was to examine the importance of the function of the BP-limb after DJB using a novel operative model., Methods: Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into the following groups: DJB with a short alimentary limb (A-limb) and long BP-limb (B-DJB group), DJB with jejunectomy (J-DJB group) in which the entire length of the jejunum used for the BP-limb of the B-DJB group was excised; and a sham operation group. Glucose tolerance, plasma bile acid levels, and the gut microbiota were assessed postoperatively., Results: Glucose tolerance was improved and weight gain was suppressed after surgery in the B-DJB group. In contrast, these effects were cancelled in the J-DJB group. The plasma levels of bile acids in the B-DJB group were greater than those in other groups. The analysis of gut microbiota showed distinct differences between the B-DJB and other groups; especially, the relative abundance of genus Bifidobacterium was much higher in the B-DJB group., Conclusion: The BP-limb played an important role in the control of weight gain, glucose tolerance, and increased plasma bile acid levels after DJB in this rat model of type 2 diabetes mellitus. Plasma bile acids and gut microbiota may be involved in these processes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Poor motor skills and differences in sensory processing have been noted as behavioral markers of common neurodevelopmental disorders. A total of 171 healthy children (81 girls, 90 boys) were investigated at age 3 to examine relations between temperament, sensory processing, and motor coordination. Using the Japanese versions of the Children's Behavior Questionnaire (CBQ), the Sensory Profile (SP-J), and the Little Developmental Coordination Disorder Questionnaire (LDCDQ), this study examines an expanded model based on Rothbart's three-factor temperamental theory (surgency, negative affect, effortful control) through covariance structure analysis. The results indicate that effortful control affects both sensory processing and motor coordination. The subscale of the LDCDQ, control during movement, is also influenced by surgency, while temperamental negative affect and surgency each have an effect on subscales of the SP-J.

Background: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in May 2013. Autism spectrum disorder (ASD) has been structured for the three subtypes of pervasive developmental disorder (PDD), but the number of impairment in social and communication dimension is not stated., Methods: The subjects were 68 children who visited the Department of Psychology and Development at Nagoya City University Hospital for the first time between the ages of 6 and 15 years old. We retrospectively re-examined the subjects using DSM-IV-TR criteria and DSM-5 criteria with two rules (two of three and one of three on the social and communication dimension) and examined the concordance rate., Results: Forty subjects were diagnosed with PDD, and 28 were not. The mean PDD subject age was 9.4 years, and mean IQ was 84.0 on the Wechsler Intelligence Scale for Children III or 62.7 on the Tanaka-Binet test. Twenty-seven (68%) of the PDD subjects were classified with ASD using DSM-5 criteria when the two of three rule was applied, while 32 (80%) were classified with ASD when the one of three rule was applied. All subjects without PDD were not diagnosed with ASD on DSM-5 criteria., Conclusion: DSM-5 criteria may exclude high functioning and older subjects from ASD because they tend to be atypical. The diagnostic procedure for DSM-5 criteria is ambiguous, especially in high functioning subjects and those diagnosed at an older age., (© 2015 Japan Pediatric Society.)

Background: The aim of the present study was to investigate the effects of the intracolonic transient receptor potential (TRP) A1 agonist allyl isothiocyanate (AITC) on colonic motility and defecation., Methods: The effects of AITC administered into the proximal colonic lumen on colonic motility and defecation were studied in neurally intact dogs equipped with strain-gauge force transducers on the colon, with or without various antagonists. Effects of intracolonic AITC were also studied in dogs with either transection/re-anastomosis (T/R) between the proximal and middle colon and complete extrinsic denervation of an ileocolonic segment., Results: AITC increased colonic motility and induced giant migrating contractions (GMCs) with defecations in 75% of experiments in neurally intact dogs. These effects were inhibited by atropine, hexamethonium, ondansetron, and HC-030031 but unaltered by capsazepine. In dogs with T/R, the increase in colonic motility was inhibited in the middle-distal colon. In dogs with extrinsic denervation, the increase in colonic motility in the distal colon was decreased., Conclusions: Intracolonic AITC stimulates colonic motility and defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of colonic enteric neurons plays an essential role in the intracolonic AITC-induced colonic motor response, while extrinsic nerves are important in occurrence and propagation of GMCs.