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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.

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.

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.