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Astrocytes are densely present in the suprachiasmatic nucleus (SCN), which is the master circadian oscillator in mammals, and are presumed to play a key role in circadian oscillation. However, specific astrocytic molecules that regulate the circadian clock are not yet well understood. In our study, we found that the water channel aquaporin-4 (AQP4) was abundantly expressed in SCN astrocytes, and we further examined its circadian role using AQP4-knockout mice. There was no prominent difference in circadian behavioral rhythms between Aqp4-/- and Aqp4+/+ mice subjected to light-dark cycles and constant dark conditions. However, exposure to constant light induced a greater decrease in the Aqp4-/- mice rhythmicity. Although the damped rhythm in long-term constant light recovered after transfer to constant dark conditions in both genotypes, the period until the reappearance of original rhythmicity was severely prolonged in Aqp4-/- mice. In conclusion, AQP4 absence exacerbates the prolonged light-induced impairment of circadian oscillations and delays their recovery to normal rhythmicity.

Independence of transfer is important for the daily activities of wheelchair users. A critical step in performing this transfer includes a pre-transfer wheelchair manipulation, and patients with Alzheimer's disease (AD) experience difficulties in learning these tasks. In this report, we present the results of a treatment focused on learning pre-transfer wheelchair manipulation and its learning course in a patient with severe AD.The patient was a 92-year-old woman with severe AD during hospitalization in a long-term care ward. Since her cognitive function was highly compromised, she required assistance for pre-transfer wheelchair manipulation. Physiotherapists implemented a treatment plan that incorporated post-behavioral praise into a practice combining errorless learning and spaced retrieval training for pre-transfer wheelchair manipulation.The patient was able to accurately perform pre-transfer wheelchair manipulation in the seventh treatment session and achieved transfer independence after 12 physiotherapy sessions.This case report suggests that practicing combined errorless learning, spaced retrieval training, and post-behavioral praise was helpful as a treatment modality for an individual with severe AD for wheelchair manipulation learning before transfer.

ObjectivesThis study examined prefrontal cortex (PFC) activation during dual-task seated stepping and walking performed by subacute stroke patients with hemiplegia and evaluated the relationship between PFC activation, frontal lobe functions, and dual-task interference.MethodsPatients with functional ambulation category (FAC) scores ≤ 2 comprised the seated stepping task group. Those with FAC scores > 2 comprised the walking task group. There were 11 patients in the seated stepping task group (mean age, 65.3±12.2 years; age range, 55-73.5 years; 7 male and 4 female patients; time since stroke onset, 45.7±9.9 days) and 11 patients in the walking task group (mean age, 65.6±15.2 years; age range, 49.5-74.5 years; 7 male and 4 female patients; time since stroke onset, 57.5±18.3 days). Both groups completed the Frontal Assessment Battery (FAB). The seated stepping task group performed the following three tasks: cognitive task (CT), normal seated stepping (NSS), and dual-task seated stepping (DTSS). The walking task group completed the following tasks: CT, normal walking (NW), and dual-task walking (DTW). The CT was a letter fluency task; this letter fluency task was simultaneously performed during seated stepping (DTSS) and walking (DTW). Changes in the oxygenated hemoglobin (O2Hb) concentration and deoxygenated hemoglobin concentration during the tasks were measured using near-infrared spectroscopy (Pocket NIRS HM; Dynasense Inc., Japan). The number of steps, walking speed, and percentage of correct responses to the CT were recorded.ResultsThe results showed that DTSS activated the PFC significantly more than performing a single task and that NSS was associated with a significantly higher difference in the hemoglobin concentration when compared to that associated with the CT, which was a single task. In the walking task group, PFC activation was significantly higher during DTW, NW, and CT (in that order), and O2Hb concentrations were significantly higher in the contralesional hemisphere than in the ipsilesional hemisphere during all tasks. Associations between PFC activation, FAB scores, and dual-task interference in the seated task group indicated significant positive correlations between FAB scores and cognitive performance with dual-task interference.ConclusionDTSS may be an effective means of activating the PFC of patients with difficulty walking.

Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer, but it does not necessarily correlate with the prognosis of breast cancer patients. Alcohol consumption in breast cancer patients was addressed in the 2022 Breast Cancer Clinical Practice Guidelines. A systematic review and meta-analysis of epidemiological studies on alcohol consumption and breast cancer recurrence, breast cancer-related mortality, all-cause mortality, and cardiovascular disease mortality in breast cancer patients was performed. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting cohort or case–control studies published until March 2021. A total of 33 studies (32 cohort studies and 1 case–control study) met the eligibility criteria; 4638 cases of recurrence, 12,209 cases of breast cancer-specific mortality, and 21,945 cases of all-cause mortality were observed. With regard to breast cancer recurrence, 7 studies assessed pre-diagnosis alcohol consumption (relative risk (RR) 1.02, 95% confidence interval (95% CI) 0.77–1.37, p = 0.88) and 3 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.85–1.10, p = 0.57), and no significant increase or decrease in risk was observed. With regard to breast cancer-related mortality, 19 studies assessed pre-diagnosis alcohol consumption (RR 1.02, 95% CI 0.93–1.11, p = 0.69), 9 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.77–1.19, p = 0.70), and no significant increase or decrease in risk was observed. With regard to all-cause mortality, 18 studies assessed pre-diagnosis alcohol consumption (RR 0.90, 95% CI 0.82–0.99, p = 0.02), 8 studies assessed post-diagnosis alcohol consumption (RR 0.88, 95% CI 0.74–1.02, p = 0.08), and pre-diagnosis alcohol consumption was associated with a significantly decreased risk. With regard to cardiovascular disease mortality and alcohol consumption, 2 studies assessed it, and the RRwas 0.47 (95% CI 0.28–0.79, p = 0.005), showing that alcohol consumption was associated with a significantly decreased risk. The limitations of this study are that drinking status was mainly based on a questionnaire survey, which is somewhat inaccurate and has many confounding factors, and the cut-off value for the maximum alcohol intake in many studies was low, and it is possible that the actual intake was only an appropriate amount. In many countries, a standard drinking amount is set, and wise decisions are required.

Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C–38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5′ UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology., 全身の体内リズムを調和させるRNA配列の発見 --体温の日内変化に合わせてしなやかに調和させる--. 京都大学プレスリリース. 2023-03-07.

This study aimed to determine the association between postoperative subjective voice function and psychological distress in patients without laryngeal nerve injury after thyroidectomy.A prospective cohort study.We investigated the factors associated with subjective voice function in patients who underwent thyroidectomy without laryngeal nerve injury between October 2018 and July 2020. The Voice Handicap Index was used to assess subjective voice function, the GRBAS (grade, roughness, breathiness, asthenia, strain) scale to assess objective voice, and the Hospital Anxiety and Depression Scale to assess psychological distress.Among 39 patients who underwent thyroidectomy, 32 had no postoperative laryngeal nerve injury. Postoperative Voice Handicap Index was significantly associated with Hospital Anxiety and Depression Scale-Anxiety score after surgery (rs = 0.448, P = .010).In this study, an association was observed between subjective voice function and anxiety following surgery. The finding suggested that nurses and medical practitioners need to consider postoperative anxiety when evaluating patients' voice function after thyroidectomy.

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction., 新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.

Introduction: Among those caring for people with dementia (PwD) at home, more than 60% feel a caregiver burden (CB), and one in three are depressed. Reducing feelings of burden and depressive states in caregiving families will improve the living environment for PwD. However, very few studies have focused on effective methods and reducing feelings of burden and depressive states of caregivers. Thus, using data from a previous study, we aimed to determine the factors associated with perceived CB and depressive states experienced by caregivers for PwD with behavioral and psychological symptoms of dementia (BPSD) at home. Methods: We performed single regression analysis on 285 participants’ data to determine the association between each item and the Zarit Caregiver Burden Interview and Center for Epidemiologic Studies-Depression Scale scores. We performed multiple regression analysis with variables considered in the single regression analysis as independent variables. Results: Severity of BPSD, caregivers’ subjective health status (SHS), time of caregiving, and depressive states were related to CB, and caregivers’ SHS and CB were related to depressive states. Conclusions: Similar to previous studies, we identified an association between family caregivers’ perceived CB and BPSD in PwD. Additionally, we found that caregivers’ SHS is commonly associated with both perceived CB and depressive states. This is a new finding. Our results suggest that interventions focusing on family caregivers’ health status can help not only to reduce family caregivers’ CB and depressive states but also stabilize patients’ symptoms and provide home-based care for a longer time.

Midwives significantly support women with unplanned pregnancies-promoting a shared perspective on the decision-making process. This study aimed to develop a scale to support midwives self-assess their practice of this vital role. Following the derivation of scale items and pilot testing, the final version of the scale was administered to 531 midwives to establish internal consistency and construct criterion-related validity. Through exploratory factor analysis, 35 items with a five-factor structure were retained to form the midwifery practice self-assessment scale to promote shared decision-making in women with unplanned pregnancies. These factors illustrate midwives' general aptitude and competencies in understanding environmental factors, collaborating with significant others and the interprofessional group, forming rapport and problem sharing, focusing on consultation content, and promoting autonomous decision-making. There were high and low scores on the scales after attending the workshops to support the decision-making of women with unplanned pregnancies. The reliability analysis showed acceptable Cronbach's alpha values for the five factors, from .85-.87. The scale was demonstrated to be a reliable and valid measure that would help improve the quality of midwives' practice. This article is protected by copyright. All rights reserved.

By the effort to identify candidate signaling molecules important for the formation of robust circadian rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, here we characterize the role of α2δ proteins, synaptic molecules initially identified as an auxiliary subunit of the voltage dependent calcium channel, in circadian rhythm formation. In situ hybridization study demonstrated that type 3 α2δ gene (α2δ3) was strongly expressed in the SCN. Mice without this isoform (Cacna2d3⁻/⁻) did not maintain proper circadian locomotor activity rhythms under a constant light (LL) condition, whereas under a constant dark (DD) condition, these mice showed a similar period length and similar light-responsiveness as compared to wild type mice. Reflecting this behavioral phenotype, Cacna2d3⁻/⁻ mice showed a severely impaired Per1 expression rhythm in the SCN under LL, but not under DD. Cultured SCN slices from Per1-luc transgenic Cacna2d3⁻/⁻ mice revealed reduced synchrony of Per1-luc gene expression rhythms among SCN neurons. These findings suggest that α2δ3 is essential for synchronized cellular oscillations in the SCN and thereby contributes to enhancing the sustainability of circadian rhythms in behavior.

The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is properly entrained by environmental light cycle. However, the molecular mechanism(s) determining the magnitude of phase shift by light is still not fully understood. The orphan G-protein-coupled receptor Gpr176 is enriched in the SCN, controls the pace (period) of the circadian rhythm in behavior but is not apparently involved in the light entrainment; Gpr176

The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system., 体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16., Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.

Circadian clocks are an endogenous internal timekeeping mechanism that drives the rhythmic expression of genes, controlling the 24 h oscillatory pattern in behaviour and physiology. It has been recently shown that post-transcriptional mechanisms are essential for controlling rhythmic gene expression. Controlling the stability of mRNA through poly(A) tail length modulation is one such mechanism. In this study, we show that

The purpose of this study was to examine the effects of simplified reminiscence practice using olfactory stimuli on depression and cognitive function in community-dwelling older adults in Japan. Accordingly, 61 individuals were randomly divided into two groups. In the intervention group, 12 sessions of reminiscence were performed using olfactory cards. In the control group, reminiscence sessions were similarly performed, but with language cards. The Geriatric Depression Scale-15 (GDS-15) was used to measure mental health status and the Five Cognitive Test was used to measure cognitive function at baseline and after completion of the intervention. The final sample included 27 participants in the intervention group and 23 participants in the control group. Basic characteristics of the participants at baseline were compared and a significant difference was observed between the two groups in age (p = 0.029). Repeated-measures analysis of covariance with age as the covariate revealed a significant interaction between time and group on the GDS-15 (p = 0.04). Furthermore, a before and after comparison using a paired t-test showed a significant difference only in the intervention group (p = 0.01). The results of this study suggest that simplified reminiscence practice using olfactory cards could serve as an intervention to help maintain the mental health of community-dwelling older adults.

Background In Japan, educational support for advance care planning is still limited, and the factors facilitating advance care planning practice have not been identified. The aim of this study is to identify the factors associated with advance care planning practice in Japan using the theory of planned behaviour. Methods We conducted a cross-sectional study through a nationwide online questionnaire survey with 446 Japanese residents aged 20 years and older. After categorizing participants into two groups based on who performed advance care planning, comparisons were made (univariate analysis) regarding attitudes towards advance care planning, willingness to perform advance care planning, subjective norms, sense of control in performing advance care planning, presence of and relationship with a family doctor, experience of seeing or using a ventilator, and degree of self-determination (Autonomy Preference Index) as well as sociodemographic data. In addition, a logistic regression analysis was performed using the factors with significant differences in the univariate analysis as independent variables and the existence of the implementation of advance care planning as a dependent variable. Results The group with advance care planning consisted of 106 participants (23.8%), and the group without advance care planning comprised 340 participants (76.2%). Through logistic regression analysis, age (odds ratio: 1.020), subjective norms (odds ratio: 3.276) and experience with mechanical ventilation (odds ratio: 1.997) were extracted as significant factors influencing advance care planning implementation. Conclusions Advance care planning may be facilitated by providing support not only to the patients but also to their family members to be positively disposed towards advance care planning and by offering comprehensive education regarding using a ventilator.

There have been no intervention studies of psychoeducation programs for schizophrenia that focus on improving subjective well-being or studies to determine the factors influencing such effects. This study aimed to examine the effects of a psychoeducation program combining traditional psychoeducation with a focus on providing knowledge and information and a new intervention to raise patients' subjective well-being and to clarity the factors affecting the program's efficacy. Subjects were 117 patients who participated in a psychoeducation program for schizophrenia between 2012 and 2018. In addition to comparing subjective well-being (Subjective Well-being under Neuroleptic Drug Treatment Short Form, Japanese version, SWNS-J) and attitudes towards drugs (Drug Attitude Inventory-10, DAI-10) before and after the program, basic information such as psychiatric symptoms was surveyed. The factors influencing the effects of the program were assessed with multiple regression analysis. Scores for SWNS-J subscales and total SWNS-J score increased significantly after the program. Higher total scores on subjective well-being after the program were significantly associated with having less severe negative symptoms and higher total subjective well-being before the program, and with more positive attitudes toward drugs after the program. These results suggest that intervention with a focus on improving subjective well-being can be an effective part of psychoeducation programs for patients with schizophrenia. The results also suggest that the level of improvement in subjective well-being gained from the program may be higher in patients with milder negative symptoms and patients with a better understanding of drug treatment.

Background and Purpose: Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with no established physiological function in vivo. The purpose of this study was to determine the role of Gpr19 in the circadian clock system. Experimental Approach: We examined whether and how the master circadian clock neurons in the suprachiasmatic nucleus (SCN) express Gpr19. By analysing Gpr19-deficient (Gpr19−/−) mice, we asked whether Gpr19 has a role in modulating free-running period and light resetting capacity of the circadian clock. Key Results: Compared with the known common core clock genes, Gpr19 was identified to show several distinct yet limited features related to the circadian clock. Gpr19 mRNA was mainly expressed in the middle-to-dorsal region of the SCN. A conserved cAMP-responsive element within the Gpr19 promoter drove the circadian expression of Gpr19. Gpr19−/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity in a 12-h light/12-h dark cycle. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. Gpr19−/− mice had a reduced capacity for phase shift to early subjective night light. The defect was only observed for phase-delay, but not phase-advance, and accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral part of the SCN, in Gpr19−/− mice. Conclusion and Implications: Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and thus may be a potential target for alleviating circadian clock disorders.

The global dietary supplement market is valued at over USD 100 billion. One popular dietary supplement, S-adenosylmethionine, is marketed to improve joints, liver health and emotional well-being in the US since 1999, and has been a prescription drug in Europe to treat depression and arthritis since 1975, but recent studies questioned its efficacy. In our body, S-adenosylmethionine is critical for the methylation of nucleic acids, proteins and many other targets. The marketing of SAM implies that more S-adenosylmethionine is better since it would stimulate methylations and improve health. Previously, we have shown that methylation reactions regulate biological rhythms in many organisms. Here, using biological rhythms to assess the effects of exogenous S-adenosylmethionine, we reveal that excess S-adenosylmethionine disrupts rhythms and, rather than promoting methylation, is catabolized to adenine and methylthioadenosine, toxic methylation inhibitors. These findings further our understanding of methyl metabolism and question the safety of S-adenosylmethionine as a supplement., 過剰なS-アデノシルメチオニンは、メチル化を阻害し生体リズムを障害する. 京都大学プレスリリース. 2022-04-20.

Calcium signaling is pivotal to the circadian clockwork in the suprachiasmatic nucleus (SCN), particularly in rhythm entrainment to environmental light-dark cycles. Here, we show that a small G-protein Gem, an endogenous inhibitor of high-voltage-activated voltage-dependent calcium channels (VDCCs), is rapidly induced by light in SCN neurons via the calcium (Ca²⁺)-mediated CREB/CRE transcriptional pathway. Gem attenuates light-induced calcium signaling through its interaction with VDCCs. The phase-shift magnitude of locomotor activity rhythms by light, at night, increases in Gem-deficient (Gem⁻/⁻) mice. Similarly, in SCN slices from Gem⁻/⁻ mice, depolarizing stimuli induce larger phase shifts of clock gene transcription rhythms that are normalized by the application of an L-type VDCC blocker, nifedipine. Voltage-clamp recordings from SCN neurons reveal that Ca²⁺ currents through L-type channels increase in Gem⁻/⁻ mice. Our findings suggest that transcriptionally activated Gem feeds back to suppress excessive light-evoked L-type VDCC activation, adjusting the light-induced phase-shift magnitude to an appropriate level in mammals., 光誘導物質による新しい体内時計の同調制御機構 --光により誘導される神経細胞の活動抑制物質の発見--. 京都大学プレスリリース. 2022-05-26.

We aimed to determine how prefrontal cortex activation and gait speed during walking is affected by cognitive dysfunction and dual-tasking. Eleven and 14 participants were included in the MOCA-J (Japanese version of the Montreal Cognitive Assessment score)26 (age, 76.0 ± 5.7 years; sex, six men and five women) and the MOCA-J ≥ 26 groups (age 73.9 ± 4.3 years; sex, seven men and seven women), respectively. We measured prefrontal cortex oxygenated hemoglobin (oxy-Hb) levels (using Pocket NIRS HM), and gait speed during normal and dual-task walking (a letter fluency task was added). The oxy-Hb levels were significantly lower in the MOCA-J26 group than in the MOCA-J ≥ 26 group during dual-task walking. The gait speed was significantly lower during dual-task walking, compared with normal walking, in the MOCA-J26group.These results may have been influenced by the compensatory mechanisms in the frontal lobe.

The S-adenosylhomocysteine (SAH) hydrolyzing enzyme AHCY functionally links the circadian clock to methionine metabolism., Circadian gene expression driven by transcription activators CLOCK and BMAL1 is intimately associated with dynamic chromatin remodeling. However, how cellular metabolism directs circadian chromatin remodeling is virtually unexplored. We report that the S-adenosylhomocysteine (SAH) hydrolyzing enzyme adenosylhomocysteinase (AHCY) cyclically associates to CLOCK-BMAL1 at chromatin sites and promotes circadian transcriptional activity. SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)–dependent methyltransferases, and timely hydrolysis of SAH by AHCY is critical to sustain methylation reactions. We show that AHCY is essential for cyclic H3K4 trimethylation, genome-wide recruitment of BMAL1 to chromatin, and subsequent circadian transcription. Depletion or targeted pharmacological inhibition of AHCY in mammalian cells markedly decreases the amplitude of circadian gene expression. In mice, pharmacological inhibition of AHCY in the hypothalamus alters circadian locomotor activity and rhythmic transcription within the suprachiasmatic nucleus. These results reveal a previously unappreciated connection between cellular metabolism, chromatin dynamics, and circadian regulation.

OBJECTIVE To determine the changes in motor function and health-related quality of life after pancreatectomy and identify factors influencing postoperative physical functioning in health-related quality of life. METHODS This single-centre, prospective, observational study measured 6-min walking distance, grip strength, knee extension strength and health-related quality of life variables in patients with pancreatic cancer, before and after surgery. Paired t- and Wilcoxon signed-rank tests were used to compare pre- and postoperative motor function and health-related quality-of-life variables. Factors associated with postoperative physical functioning scores of health-related quality of life were assessed using multiple regression analysis. RESULTS Fifty-nine individuals were enrolled. Motor function values decreased significantly postoperatively, including 6-min walking distance (mean ± standard deviation: 402.5 ± 95.4 vs. 497.7 ± 80.4 m, p

This study aimed to explore the competencies of health care practitioners who promote shared decision-making (SDM)-based care for women facing an unplanned pregnancy in Japan. We conducted semistructured interviews with 12 care providers who are pioneers in care for women facing an unplanned pregnancy and adopted a modified grounded theory approach for data analysis. A three-step model for shared decision making in practice (team talk, option talk, and decision talk) was used as a reference. The answers given by the care providers were analyzed to identify the competencies involved in shared decision making. We identified three stages: (i) building trust and promoting women's expression; (ii) discussing women's real needs; and (iii) exploring the intentions and goals expressed by women and finding the best choices while promoting women's autonomy in decision-making. The coordination between the support of partners, families, and professionals, and the care provided to strengthen women's identities facilitated shared decision making. Women facing an unplanned pregnancy can benefit from interventions designed to improve shared decision making. A key component of shared decision making-based care relates to practitioners' raised awareness toward their roles and responsibilities: developing good communication skills and fostering collaboration between all stakeholders.

The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies.

Background The physical and mental impacts of breast cancer diagnosis on women are substantial. Several studies have investigated the negative mental health effects of breast cancer. However, in recent years, there has also been growing interest in post-traumatic growth, a positive response to stressful events. Considering positive psychology focuses on such virtues, proactive coping theory was chosen as a theoretical guide. This study investigates how breast cancer patients’ post-traumatic growth is associated with proactive coping and mental well-being. Methods A self-administered questionnaire survey was conducted with 80 breast cancer patients aged 20–70 years attending an outpatient clinic. The survey was conducted using the Posttraumatic Growth Inventory-Japanese version (PTGI-J), Proactive Coping Inventory-Japanese version and the Japanese version of the General Health Questionnaire. Single regression and multiple regression analyses with PTGI-J as the dependent variable were performed. Results The multiple regression analysis extracted proactive coping (P = 0.006), emotional support seeking (P = 0.004) and avoidance coping (P = 0.001) as factors associated with post-traumatic growth in breast cancer patients. Conclusions These results suggest that using proactive coping for conflicts caused by a breast cancer diagnosis and temporary avoidant coping for daily stresses during the treatment process may enhance post-traumatic growth while preventing deterioration in mental well-being. Additionally, seeking emotional support is important for post-traumatic growth.

The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies., Fustin et al. reveal the evolutionarily conserved link between methyl metabolism and biological clocks. This study suggests the possibility of translating fundamental understanding of methylation deficiencies to clinical applications.

G-protein-coupled receptors (GPCRs) are important drug targets with diverse therapeutic applications. However, there are still more than a hundred orphan GPCRs, whose protein functions and biochemical features remain unidentified. Gpr176 encodes a class-A orphan GPCR that has a role in circadian clock regulation in mouse hypothalamus and is also implicated in human breast cancer transcriptional response. Here we show that Gpr176 is N-glycosylated. Peptide-N-glycosidase treatment of mouse hypothalamus extracts revealed that endogenous Gpr176 undergoes N-glycosylation. Using a heterologous expression system, we show that N-glycosylation occurs at four conserved asparagine residues in the N-terminal region of Gpr176. Deficient N-glycosylation due to mutation of these residues reduced the protein expression of Gpr176. At the molecular function level, Gpr176 has constitutive, agonist-independent activity that leads to reduced cAMP synthesis. Although deficient N-glycosylation did not compromise this intrinsic activity, the resultant reduction in protein expression was accompanied by attenuation of cAMP-repressive activity in the cells. We also demonstrate that human GPR176 is N-glycosylated. Importantly, missense variations in the conserved N-glycosylation sites of human GPR176 (rs1473415441; rs761894953) affected N-glycosylation and thereby attenuated protein expression and cAMP-repressive activity in the cells. We show that N-glycosylation is a prerequisite for the efficient protein expression of functional Gpr176/GPR176.

Chronic jet lag, a model of shiftwork, increases mortality in aged mice. One potential reason for this association is that the chronic desynchronization between the internal clock phase and the environmental light/dark (LD) cycle might increase the mortality rate. However, this hypothesis has not been examined because of the lack of an appropriate animal model to prove this speculation. Here, we found that rapidly entrainable vasopressin receptor V1a–/–V1b–/– mice showed lower mortality under a chronic jet lag condition. Moreover, we found that pharmacological inactivation of V1a and V1b signaling decreased mortality even in aged wild-type mice, thus providing a potential pharmaceutical intervention for shiftwork-related health problems., 慢性時差環境下での老齢マウスの生存率改善に成功 --シフトワーカーの病態への創薬に期待--. 京都大学プレスリリース. 2018-07-20.

Background There has been little research on reminiscence cues and their effectiveness. The purpose of the present study was to measure the effects of reminiscence practice using olfactory stimuli on the mental health and cognitive functions of community-dwelling elderly individuals. Methods Written consent was obtained from 72 eligible community-dwelling elderly individuals. They were non-randomly divided into an intervention group and a control group. In the intervention group (n = 35), reminiscence practice was carried out bi-weekly using olfactory stimulation as the cue for eight sessions. In the control group (n = 37), reminiscence practice was carried out without olfactory stimulation. The Geriatric Depression Scale-15 and the Five-cog Test were used as the methods of assessment at baseline and again after completion of the intervention. Participants in the final analysis were 27 individuals in the intervention group and 33 individuals in the control group. Results At baseline, a significant difference was seen between the groups depending on the existence of a spouse. Repeated measures analysis of covariance with the existence of a spouse as a covariate showed a significant difference between the two groups in changes in Geriatric Depression Scale-15 scores (P = 0.038). Furthermore, analysis of the participants sorted into a depression symptoms group and a non-depression symptoms group showed a significant group main effect (P = 0.033) and interaction (P = 0.049) in the depression symptoms group. Conclusion The results suggest that reminiscence intervention using olfactory stimulation may maintain the mental health of community-dwelling elderly individuals.

Daily body temperature rhythm (BTR) is essential for maintaining homeostasis. BTR is regulated separately from locomotor activity rhythms, but its molecular basis is largely unknown. While mammals internally regulate BTR, ectotherms, including Drosophila, exhibit temperature preference rhythm (TPR) behavior to regulate BTR. Here, we demonstrate that the diuretic hormone 31 receptor (DH31R) mediates TPR during the active phase in Drosophila. DH31R is expressed in clock cells, and its ligand, DH31, acts on clock cells to regulate TPR during the active phase. Surprisingly, the mouse homolog of DH31R, calcitonin receptor (Calcr), is expressed in the suprachiasmatic nucleus (SCN) and mediates body temperature fluctuations during the active phase in mice. Importantly, DH31R and Calcr are not required for coordinating locomotor activity rhythms. Our results represent the first molecular evidence that BTR is regulated distinctly from locomotor activity rhythms and show that DH31R/Calcr is an ancient specific mediator of BTR during the active phase in organisms ranging from ectotherms to endotherms.

Micturition behavior follows regular day/night fluctuations, and unwanted increase in micturition could occur during night in jet lag condition. To clarify the effect of jet lag on micturition behavior, we simultaneously detected circadian micturition patterns and locomotor activity rhythms of mice under experimental jet lag conditions, by applying the improved automated Voided Stain on Paper (aVSOP) method. When wild-type (WT) mice were phase-advanced for 8 hours, day-night variation of micturition was disrupted suddenly, and this irregular daily micturition continued until 8 days, although their activity rhythms entrained gradually day by day until 8 days. We also examined how jet lag induced changes of micturition in Per-null mice lacking Per1, Per2 and Per3 genes, whose endogenous clock is completely disrupted. We found both micturition and locomotor activity of Per-null mice promptly entrained to the new LD cycle. These findings suggest that the irregular micturition during jet lag is caused along with the gradual shift of the endogenous clock, and paradoxically, jet lag-associated abnormality was absent when endogenous circadian oscillations were genetically disrupted.

Jet-lag symptoms arise from temporal misalignment between the internal circadian clock and external solar time when traveling across multiple time zones. Light is known as a strong timing cue of the circadian clock. We here examined the effect of daily light on the process of jet lag by detecting c-Fos expression in the master clock neurons in the suprachiasmatic nucleus (SCN) under 8-hr phase-advanced jet lag condition. In WT mice, c-Fos-immunoreactivity was found at 1–2 hours on the first day after light/dark (LD) phase-advance. This induction was also observed on the second and third days, although their levels were diminished day by day. In contrast, c-Fos induction in the SCN of V1a–/–V1b–/– mice, which show virtually no jet lag symptoms even after 8-hr phase-advance, was only detected on the first day. These results indicate that external light has affected SCN neuronal activity for 3 days after LD phase-advance in WT mice suggesting the continuous progress of activity change of SCN neurons under jet lag conditions. Noteworthy, limited c-Fos induction in V1a–/–V1b–/– SCN is also consistent with the rapid reentrainment of the SCN clock in mutant mice after 8-hr LD phase-advance.

Liver metabolism undergoes robust circadian oscillations in gene expression and enzymatic activity essential for liver homeostasis, but whether the circadian clock controls homeostatic self-renewal of hepatocytes is unknown. Here we show that hepatocyte polyploidization is markedly accelerated around the central vein, the site of permanent cell self-renewal, in mice deficient in circadian Period genes. In these mice, a massive accumulation of hyperpolyploid mononuclear and binuclear hepatocytes occurs due to impaired mitogen-activated protein kinase phosphatase 1 (Mkp1)-mediated circadian modulation of the extracellular signal-regulated kinase (Erk1/2) activity. Time-lapse imaging of hepatocytes suggests that the reduced activity of Erk1/2 in the midbody during cytokinesis results in abscission failure, leading to polyploidization. Manipulation of Mkp1 phosphatase activity is sufficient to change the ploidy level of hepatocytes. These data provide clear evidence that the Period genes not only orchestrate dynamic changes in metabolic activity, but also regulate homeostatic self-renewal of hepatocytes through Mkp1-Erk1/2 signaling pathway., Circadian clock regulates hepatic gene expression and functions. Here Chao et al. show that alteration of circadian clock genes by Period deletion induces polyploidy in hepatocytes due to impaired regulation of Erk signaling by mitogen-activated protein kinase phosphatase 1.

To identify a specific sensorimotor impairment feature of autism spectrum disorder (ASD), we focused on temporal processing with millisecond accuracy. A synchronized finger-tapping task was used to characterize temporal processing in individuals with ASD as compared to typically developing (TD) individuals. We found that individuals with ASD showed more variability in temporal processing parameters than TD individuals. In addition, temporal processing instability was related to altered motor performance. Further, receiver operating characteristic (ROC) curve analyses indicated that altered temporal processing can be useful for distinguishing between individuals with and without ASD. These results suggest that instability of temporal processing with millisecond accuracy is a fundamental feature of sensorimotor impairments in ASD.

G-protein-coupled receptors (GPCRs) constitute an immensely important class of drug targets with diverse clinical applications. There are still more than 120 orphan GPCRs whose cognate ligands and physiological functions are not known. A set of circadian pacemaker neurons that governs daily rhythms in behavior and physiology resides in the suprachiasmatic nucleus (SCN) in the brain. Malfunction of the circadian clock has been linked to a multitude of diseases, such as sleeping disorders, obesity, diabetes, cardiovascular diseases, and cancer, which makes the clock an attractive target for drug development. Here, we review a recently identified role of Gpr176 in the SCN. Gpr176 is an SCN-enriched orphan GPCR that sets the pace of the circadian clock in the SCN. Even without known ligand, this orphan receptor has an agonist-independent basal activity to reduce cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for the activity of Gpr176. We also provide an overview on the circadian regulation of G-protein signaling, with an emphasis on a role for the regulator of G-protein signaling 16 (RGS16). RGS16 is indispensable for the circadian regulation of cAMP in the SCN. Developing drugs that target the SCN remains an unfulfilled opportunity for the circadian pharmacology. This review argues for the potential impact of focusing on GPCRs in the SCN for the purpose of tuning the body clock.

The Gm7325 gene, bioinformatically identified in the mouse genome, encodes a small protein but has not been characterized until recently. Our gene expression analysis revealed that Gm7325 transcription is remarkably upregulated in injured skeletal muscle tissues. Activated satellite cells and immature myotubes were densely decorated with positive signals for Gm7325 mRNA in in situ hybridization analysis, while no obvious signals were observed in quiescent satellite cells and mature myofibers. In the 5'-flanking regions of mouse Gm7325 and its human homologue, conserved E-box motifs for helix-loop-helix transcription factors are repeatedly arranged around the putative promoter regions. Reporter gene assays suggested that MyoD, a master transcription factor for myogenesis, binds to the conserved E-box motifs to activate Gm7325 expression. Therefore, Gm7325, as a novel MyoD-target gene, is specifically induced in activated satellite cells, and may have an important role in skeletal myogenesis.

Cancer therapy-induced cognitive impairment adversely affects the quality of life of patients with cancer but cannot be detected by neuropsychological tests.This study aimed to validate a Japanese version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) version 3, which is a self-report measure of the cognitive concerns of patients with cancer.The FACT-Cog was translated into Japanese and pilot tested with five patients with breast cancer and five patients with hematologic malignancy. Study participants were recruited in Hiroshima University Hospital and Kagawa Breast Clinic in Hiroshima, Japan. Patients with breast cancer (N = 236) responded to the resultant assessment and Functional Assessment of Cancer Therapy-General version 4. The internal consistency and concurrent and construct validity of the FACT-Cog were examined.The Cronbach's alphas of the four FACT-Cog subscales, namely, CogPCI, CogOth, CogPCA, and CogQOL, were 0.95, 0.73, 0.93, and 0.88, respectively. The item-to-domain correlations ranged from 0.211 to 0.920. Most of the FACT-Cog subscales were significantly correlated with other subscale and total scores (r = 0.133-0.425). Structural equation modeling was barely acceptable (χ2 = 1361.8, df = 489, P 0.001; goodness of fit index = 0.731, adjusted goodness of fit index = 0.691, comparative fit index = 0.848, root-mean-square error of approximation = 0.087).The Japanese version of the FACT-Cog is a valid and reliable self-report measure of the cognitive function of patients with breast cancer. Its utility to clinicians and researchers in measuring the cognitive concerns of patients with cancer in Japan will serve as a further test of its validity.

Non-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E′-box cis-element in the promoter region of the core clock gene Per2. The Per2 E′-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E′-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E′-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity., The circadian transcription factors BMAL1:CLOCK bind to E/E′-boxes in gene regulatory elements of their targets and facilitate rhythmic expression. Here, the authors mutate the Per2 promoter E’′-box in mice and observe that cell- and tissue-autonomous oscillations are dampened and that animals are less susceptible to jet lag.

The methyl cycle is a universally conserved metabolic pathway operating in prokaryotes and eukaryotes. In this pathway, the amino acid methionine is used to synthesize S-adenosylmethionine, the methyl donor co-substrate in the methylation of nucleic acids, histone and non-histone proteins and many other molecules within the cell. The methylation of nucleic acids and proteins is the foundation of epigenetic and epitranscriptomic regulations of gene expression, but whether the methyl cycle centrally regulates gene expression and function by controlling the availability of methyl moieties is poorly understood.From cyanobacteria to humans, a circadian clock that involves an exquisitely regulated transcription-translation-feedback loop driving oscillations in gene expression and orchestrating physiology and behavior has been described. We reported previously that inhibition of the methyl cycle in mammalian cells caused the lengthening of the period of these oscillations, suggesting the methyl cycle may indeed act as a central regulator of gene expression, at least in mammals. Here, we investigated whether the methyl cycle, given its universal presence among living beings, regulates the circadian clock in species across the phylogenetic tree of life.We reveal a remarkable evolutionary conservation of the link between the methyl cycle and the circadian clock. Moreover, we show that the methyl cycle also regulates the somite segmentation clock, another transcription-translation negative feedback loop-based timing mechanism that orchestrate embryonic development in vertebrates, highlighting the methyl cycle as a master regulator of biological clocks.SIGNIFICANCE STATEMENTHere we reveal that the methyl cycle, a universal metabolic pathway leading to the synthesis of S-adenosylmethionine, the methyl donor co-substrate in virtually all transmethylation reactions within the cell, is a conserved regulator of biological clocks. These discoveries highlight the methyl cycle as a metabolic hub that regulates gene expression via the availability of methyl moieties for the methylation of nucleic acids, proteins and many other molecules with the cell.

We aimed to determine whether voice rehabilitation after radiotherapy improves the quality of life (QOL), voice function, and self-rated voice function in patients with laryngeal cancer. We searched CENTRAL, MEDLINE, EMBASE, PEDro, and World Health Organization International Clinical Trials Registry Platform for randomized controlled trials published between inception and October 2018. The primary outcome was QOL, adverse events and mortality. Secondary outcomes included voice function and self-rated voice function. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. Three trials (enrolling 122 patients) compared voice rehabilitation to usual care or no intervention after radiotherapy. Voice rehabilitation did not significantly improve any QOL scores. Data on adverse events and mortality were not available in any of the trials. Voice rehabilitation did not improve any voice function scores, such as jitter (mean difference: – 0.48 [– 1.27 to 0.32]), shimmer (mean difference: – 0.04 [– 0.27 to 0.19]), maximum phonation time (mean difference: 1.54 [– 1.13 to 4.22]), and the grade, roughness, breathiness, asthenia, and strain scale (mean difference: – 0.39 [– 2.59 to 1.80]). Voice rehabilitation also did not improve the voice handicap index, which was used as a self-rated voice function score (mean difference: 5.54 [– 2.07 to 13.16]). The certainty of the evidence was graded as low for primary and secondary outcomes. Voice rehabilitation for patients with laryngeal cancer after radiotherapy might not improve QOL, voice function, and self-rated voice function. Pre-specified voice rehabilitation programs may not be necessary for all patients with laryngeal cancer after radiotherapy.

Background Like most women, female nurses in the workforce experience life events such as marriage, childbirth, and child-rearing, and carry out numerous personal roles. This may result in an increase in various demands for nurses, and coping with these roles may promote work engagement. However, few studies have focused on work engagement or spillover effects, including those in the family domain, in female nurses with multiple roles. In the present study, we aimed to examine work engagement in female nurses and investigate its relationship with factors such as the presence or absence of multiple personal roles. Methods The subjects of this study were 1225 female nurses working at three general hospitals, each with at least 200 hospital beds in Fukuoka Prefecture, Japan. The cross-sectional design of the study used anonymous self-administered questionnaires. Responses were received from 650 nurses (response rate 53.1%), of which 612 were valid (valid response rate 50.0%). Multiple regression analysis was performed on the 612 responses regarding associations between work engagement and the presence or absence of multiple roles (role as a wife or mother), spillover effects, coping characteristics, job demands, and job resources. Results In general, the work engagement of female nurses was low, as is the case with other female workers in Japan, but work engagement was higher among female nurses with multiple roles than among those without. The regression analysis showed that factors associated with better work engagement in female nurses were family-to-work positive spillover, job resources, coping strategies including “changing a point of view,” “active solution for problems,” “avoidance and suppression,” and the presence of multiple roles. Conclusions The results indicate that in addition to resources in the work domain, a family-to-work positive spillover effect, which is a variable in the non-work domain, may also promote energetic work among female nurses. Therefore, it is necessary for nurses to receive support at work and use effective coping strategies.

In Japan, long-term hospitalization of patients with schizophrenia is still prevalent, even though the focus of psychiatric care is shifting from hospitals to the community. Difficulties in discharge planning often arise because clinical staff members’ functional assessment differs from that of patients’ self-assessment. Therefore, we attempted to identify characteristics related to these perceptual differences to promote the development of more effective approaches toward the discharge and societal reintegration of patients with schizophrenia undergoing prolonged hospitalization. Forty-eight long-term inpatients (23 men and 25 women with a mean age of 60.72 years) with schizophrenia were examined using the Schizophrenia Cognition Rating Scale Japanese version (SCoRS-J), Life Skills Profile (LSP), and Profile of Mood States- (POMS-) Brief Form. Differences between patients’ self-ratings and clinical staff members’ ratings on the SCoRS-J were used to divide patients into overestimators, underestimators, and accurate raters. These groups were then comparatively analyzed. Accordingly, overestimators displayed significantly severe cognitive dysfunction on the SCoRS-J objective ratings (p=.001) and significantly less difficulty on the SCoRS-J subjective ratings (p=.002) as compared to underestimators. Overestimators also scored significantly lower on the communication (p=.012) and responsibility (p=.021) LSP subscales compared to underestimators, and the total LSP score for overestimators was significantly lower compared to accurate raters (p=.036) and underestimators (p=.009). However, underestimators displayed significantly higher confusion on the titular POMS subscale than did overestimators (p=.021). These findings indicate that, among the three groups, overestimators scored lowest for objectively rated functioning. In contrast, underestimators attained the highest functioning; however, they were also confused. Clinical staff should examine how patients’ self-perceptions deviate from the perceptions of staff and implement an appropriate approach considering the patient characteristics revealed from the results of this study.

Background It has become necessary to develop mental health management methods that do not require specialized skills or tools to implement. With this in mind, we performed a subjective and objective investigation of the stress-reducing effect of hearing laughter. Methods Ninety healthy students were randomly assigned to a laughter (n = 45) or rest (n = 45) group. Both groups were then administered the Uchida-Kraepelin test for 15 min, which served as a stress-loading method. The laughter group listened to a specially prepared CD for five minutes, while the rest group rested for five minutes. The participants’ subjective stress level was assessed using a visual analogue scale and their physiological status was assessed by measuring blood pressure and monitoring heart rate variability. Results The visual analogue scale score for subjective stress was found to decrease significantly in both the laughter and rest groups after the intervention. However, a two-way repeated-measures analysis of variance revealed significant interaction and main effects for the change in heart rate and the natural logarithm of the high-frequency component of heart rate variability (lnHF). A post-hoc analysis using Dunnett’s test showed that hearing laughter caused the lnHF to significantly increase compared to that recorded during the Uchida-Kraepelin test and the rest period. Conclusions These results suggest that hearing laughter might produce a relaxing effect by increasing parasympathetic nervous activity. This would make it an easily accessible method for improving the recovery process of the autonomic nervous system after a stress-loading task that does not require specialized skills or tools. Trial registration UMIN000016422. Retrospectively registered on 2 February 2015. Electronic supplementary material The online version of this article (10.1186/s13030-018-0141-0) contains supplementary material, which is available to authorized users.

Background Objective evaluation is important to achieve an effective intervention. However, there are limited assessment tools to easily apply to autism spectrum disorder (ASD) individuals with various severities in the clinical setting. This study aimed to characterize the timing control ability of ASD individuals and clarify the relationship between timing control ability and ASD severity level in order to establish an assessment tool for ASD function. Method We developed a simple touchscreen-based task for evaluate motor timing control ability and used two types of sensorimotor timing controls (i.e., simple timing and delayed timing tasks) in ASD (n = 77) and typically developing (TD) individuals (n = 87). Results Each participant with ASD completed the simple timing task. Regarding the delayed timing task, two participants in the ASD group were excluded as they faced difficulties when conducting the task according to the instruction. Accuracy of motor-timing control was significantly lower in participants with ASD than in those with TD for each timing task. The mean timing error in the adaptive timing control were correlated with clinically evaluated ASD severity and participant age in the ASD group. Furthermore, receiver operating characteristic curve analysis indicated that altered motor timing control is useful for distinguishing individuals with and without ASD (area under the curve = .845). Conclusions We showed that our assessment tool accurately assessed timing control ability of individuals with ASD, regardless of the varying ranges of symptomatic severities, and served as a useful tool for capturing the overall severity of such a heterogeneous disorder, which may lead to more effective therapies for ASD.

Falls are adverse events affecting psychiatric inpatients that can lead to external injuries, fractures, and death. However, none have attempted to examine fall-related factors, particularly focused on balance, specifically among inpatients with schizophrenia. The present preliminary study aimed to assess the association between falls and balance in patients with schizophrenia. The authors performed baseline assessments of background factors, postural sway, and maximum step length in 120 patients with schizophrenia hospitalized in the psychiatric ward. A prospective 3-month follow-up was conducted, and participants were divided into a fall or non-fall group according to their history of falls during the follow-up. Variance among individual variables was compared between the fall group and non-fall group using the t-test, Mann–Whitney U test, and chi-square test. A total of 16 participants experienced falls in the 3-month follow-up period (13.3%). Comparative factor analysis revealed significant differences between the fall and non-fall groups in terms of the presence or absence of falls within 3 months before follow-up (p = 0.002) and Romberg quotients for sway length (p = 0.02). These findings suggest that fall history could be considered a predictor of future falls, which could help with fall prevention, and that assessment of visual contribution to postural control using the Romberg quotient could play an important role in fall prevention.