Structure of full-length ERGIC-53 in complex with MCFD2 for cargo transport.

ERGIC-53 transports certain subsets of newly synthesized secretory proteins and membrane proteins from the endoplasmic reticulum to the Golgi apparatus. Despite numerous structural and functional studies since its identification, the overall architecture and mechanism of action of ERGIC-53 remain unclear. Here we present cryo-EM structures of full-length ERGIC-53 in complex with its functional partner MCFD2. These structures reveal that ERGIC-53 exists as a homotetramer, not a homohexamer as previously suggested, and comprises a four-leaf clover-like head and a long stalk composed of three sets of four-helix coiled-coil followed by a transmembrane domain. 3D variability analysis visualizes the flexible motion of the long stalk and local plasticity of the head region. Notably, MCFD2 is shown to possess a Zn2+-binding site in its N-terminal lid, which appears to modulate cargo binding. Altogether, distinct mechanisms of cargo capture and release by ERGIC- 53 via the stalk bending and metal binding are proposed.

Challenges and solutions for discharge support of elderly people in the acute care ward: Interviews with community-based integrated care supporters and patients in Tokyo, Japan.

Japan, which has become the country with the longest-living people in the world due to rapid population aging, has an insurer function for each local government and socialized long-term care under a public system. Japan aims to build a Community-based Integrated Care System (CICS) for each municipality with the goal of integrating medical care and long-term care. However, despite the policy and management studies, the challenges and solutions for discharge support by the parties have not yet been clarified. This study aimed to obtain suggestions on challenges and solutions for discharge support in the acute care wards for the elderly for community-based integrated care support providers and patients in Kita Ward, Tokyo. Semi-structured interviews were conducted, and the obtained data were a priori analyzed by a deductive thematic analysis using a conceptual framework for integrated care based on the integrative functions of primary care. The challenges were found to include: i) disparity between medical and lifestyle perspectives, ii) competencies of medical and care workers at homes, iii) discharge support challenges related to the elderly themselves, iv) nursing care dependent on family; and v) the impact of payment of medical service in the health insurance system and payment of long-term care services. The solution that can be applied at the local government level was community connection. While aiming to build a CICS for each local government, there was a contradiction in that the challenges and solutions required examination at the national and prefectural levels.

Butyrate, Valerate, and Niacin Ameliorate Anaphylaxis by Suppressing IgE-Dependent Mast Cell Activation: Roles of GPR109A, PGE2, and Epigenetic Regulation.

Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during the fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate the development and function of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) remain unclear. In the current study, we analyzed the function and gene expression of mouse MCs in the presence of SCFAs in vitro and in vivo. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis and passive cutaneous anaphylaxis in mice. The majority of SCFAs, particularly propionate, butyrate, valerate, and isovalerate, suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by the Gi protein inhibitor pertussis toxin and by the knockdown of Gpr109a. A treatment with the HDAC inhibitor trichostatin A also suppressed IgE-mediated MC activation and reduced the surface expression level of FcεRI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly reduced by PGE2 but not by PGD2. Furthermore, SCFAs enhanced PGE2 release from stimulated MCs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist, but not by an EP4 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by cyclooxygenase inhibitors and the EP3 antagonist. We conclude that SCFAs suppress IgE-mediated activation of MCs in vivo and in vitro involving GPR109A, PGE2, and epigenetic regulation.

Metroplasty increases the take-home baby rate by reducing pregnancy loss without changing the chance of conception in women with septate uterus: a retrospective, single-center, observational study.

BACKGROUND: Although abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center. METHODS: This retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins' method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women. RESULTS: Seventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio. CONCLUSIONS: Both abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy. TRIAL REGISTRATION: Not applicable.

Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis.

HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.

Impact of longer working hours on fathers' parenting behavior when their infants are 6 months old: The Japan Environment and Children's Study.

Objective: Long working hours have been suggested to affect fathers' parenting behavior, but previously reported findings have been inconsistent. This study examined the association between the working hours and parenting behavior of fathers while accounting for other factors related to their parenting behavior, using data from the Japan Environment and Children Study (JECS), a large cohort study in Japan. Methods: Data from 43,159 father-mother pairs were analyzed. The mother assessed the father's frequency of seven parenting behaviors at 6 months after delivery. Then, each behavior was classified into a high-engagement group (always and sometimes) or a low-engagement group (rarely and never). The father's weekly working hours was obtained from his responses and was classified into six levels. Results: Logistic regression analysis showed that after adjustment for covariates, fathers' weekly working hours was inversely associated with the frequency of all parenting behaviors examined in this study (p for trend <0.0001). Compared with fathers working ≥0 to ≤40 h per week, those working >65 h per week showed the following adjusted odds ratios (95% confidence intervals) for low engagement in parenting behaviors: playing at home, 2.38 (2.08-2.72); changing diapers, 2.04 (1.89-2.20); and bathing the child, 2.01 (1.84-2.18). Conclusion: This study suggests that the greater time constraints imposed by longer working hours constitute a major factor that discourages fathers from engaging in childrearing behavior. Intervention targeting long working hours could contribute to measures aimed at promoting high-engagement parenting behaviors among fathers.

[Current issues related to education in the five core disciplines of public health at the school of public health in a private university].

Objectives　In Japan, schools of public health (SPH) have engaged in professional education focusing on five core disciplines: epidemiology, biostatistics, social and behavioral science, health policy and management, and occupational and environmental health. However, empirical information is lacking regarding the current state of this education and its associated challenges in Japan. In this article, we showcase this issue, using the master of public health (MPH) course at Teikyo University Graduate School of Public Health (Teikyo SPH) as an example.Methods　We summarized the current objectives and classes required to complete the MPH course at Teikyo SPH, using the course guideline published in 2022. Current issues and possible future directions in the course were summarized based on the opinions of Teikyo SPH faculty members.Results　For epidemiology, lectures and exercises were designed to focus on how to formulating public health issues, collecting and evaluating data, and causal inference. Issues related to the design included ensuring that students had the necessary skills to apply epidemiology to emerging issues, and catching the course up with evolving techniques. For biostatistics, lectures and exercise classes focused on understanding data and statistics, as well as performing analyses. Issues included the understanding of theories, setting the course level, and a lack of appropriate education materials for emerging analytical methods. For social and behavioral science, lectures and exercise classes focused on understanding human behaviors and actions for problem solving. Issues included learning various behavioral theories in a limited timeframe, the gap between the lectures and various needs, and nurturing professionals who had the skills to perform in practical settings. For health policy and management, lectures, exercise classes, and practical training classes focused on identifying and solving problems in the community and around the world, and on integrating the disparate viewpoints of health economics and policy. Issues included few alumni who actually found work globally, a lack of students working in local or central administrations, and insufficient perspectives on rational/economic thinking and macro-economic transitions. For occupational and environmental health, lectures, exercise classes, and practical training classes focused on learning the occupational and environmental impacts of public health issues, and their countermeasures. Challenges included enriching the topics with regard to advanced technologies, environmental health, and socially vulnerable populations.Conclusion　Through these reflections on MPH education at Teikyo SPH, the following recommendations are considered essential in order to prepare improvements to the program: reorganizing the curriculum to meet the needs of the day, accepting students with various backgrounds, addressing the increasing knowledge and skills that need to be acquired by the students, and enhancing the powers of professors to implement changes.

Perceived Future Outcomes of Unsuccessful Treatment and Their Association with Treatment Persistence Among Type-2 Diabetes Patients: A Cross-Sectional Content Analysis.

INTRODUCTION: Despite the known strong association between patients' knowledge of outcomes of type 2 diabetes mellitus (T2DM) and treatment persistence, this knowledge in this patient population requires further clarification. The aim of our study was to reveal the perception of unsuccessful treatment outcomes among patients with T2DM and its association with treatment persistence by analysing answers to open-ended questions. METHODS: In this cross-sectional study, 106 patients with T2DM who lived in Fukushima Prefecture, Japan, had a medical record in the Fukushima National Health Insurance Organisation database and had no cognitive problems were enrolled by purposive sampling. Treatment status was defined as "non-persistent" when a participant's treatment medical record was absent for a continuous period of ≥ 6 months; otherwise, it was referred to as "persistent". We asked about the possible future problems of untreated T2DM, inductively classified the open answers into 15 codes and then statistically examined the association between these codes and treatment persistence using logistic regression analysis adjusted for age and sex. RESULTS: Persistent treatment was prevalent among participants who mentioned the code "treatment", which encompasses the terms that indicated invasiveness, such as dialysis, insulin injection, and shots (odds ratio 4.339; 95% confidence interval 1.104-17.055). CONCLUSION: Persistent treatment was prevalent among patients with T2DM who mentioned the code "treatment", suggesting that these patients may anticipate a threat due to the invasiveness of diabetes and thus participate in persistent treatment to avoid this threat. Healthcare professionals should provide appropriate information and supportive conditions to achieve both a reduced feeling of threat and persistent treatment engagement.

GPR55 contributes to neutrophil recruitment and mechanical pain induction after spinal cord compression in mice.

Pain transmission and processing in the nervous system are modulated by various biologically active substances, including lysophospholipids, through direct and indirect actions on the somatosensory pathway. Lysophosphatidylglucoside (LysoPtdGlc) was recently identified as a structurally unique lysophospholipid that exerts biological actions via the G protein-coupled receptor GPR55. Here, we demonstrated that GPR55-knockout (KO) mice show impaired induction of mechanical pain hypersensitivity in a model of spinal cord compression (SCC) without the same change in the models of peripheral tissue inflammation and peripheral nerve injury. Among these models, only SCC recruited peripheral inflammatory cells (neutrophils, monocytes/macrophages, and CD3+ T-cells) in the spinal dorsal horn (SDH), and GPR55-KO blunted these recruitments. Neutrophils were the first cells recruited to the SDH, and their depletion suppressed the induction of SCC-induced mechanical hypersensitivity and inflammatory responses in compressed SDH. Furthermore, we found that PtdGlc was present in the SDH and that intrathecal administration of an inhibitor of secretory phospholipase A2 (an enzyme required for producing LysoPtdGlc from PtdGlc) reduced neutrophil recruitment to compressed SDH and suppressed pain induction. Finally, by screening compounds from a chemical library, we identified auranofin as a clinically used drug with an inhibitory effect on mouse and human GPR55. Systemically administered auranofin to mice with SCC effectively suppressed spinal neutrophil infiltration and pain hypersensitivity. These results suggest that GPR55 signaling contributes to the induction of inflammatory responses and chronic pain after SCC via the recruitment of neutrophils and may provide a new target for reducing pain induction after spinal cord compression, such as spinal canal stenosis.

Maternal dietary intake of fish and child neurodevelopment at 3 years: a nationwide birth cohort-The Japan Environment and Children's Study.

Background: Results on the association between fish intake during pregnancy and a reduction in neurodevelopmental delays in children have been inconsistent, with some reports finding an association and others finding none. Because neurodevelopmental delays are more pronounced at the age of 3 years, their association needs to be examined at this age. Methods: After exclusion and multiple imputation from a dataset comprising 104,057 records from the Japan Environment and Children's Study, logistic regression analysis was conducted in quintiles to evaluate the association between maternal fish intake during pregnancy and child neurodevelopment at age 3 years in 91,909 mother-child pairs. The Food Frequency Questionnaire (FFQ), validated in the Japan Public Health Center-Based Prospective Study for the Next Generation, was used to assess maternal fish intake during pregnancy. The Ages and Stages Questionnaires-3 was used to assess children's neurodevelopment in five domains: communication, gross motor, fine motor, problem-solving, and personal-social. Results: Consistently lower odds were found for the highest vs. lowest quintile for the domains of communication, fine motor, problem-solving, and personal-social but not gross motor skills, with adjusted odd ratios (95% confidence intervals) of 0.89 (0.80-0.998), 0.90 (0.83-0.97), 0.86 (0.80-0.94), 0.87 (0.77-0.98), and 1.04 (0.94-1.16), respectively. The trend for lower odds of symptoms of neurodevelopmental delays across quintiles of higher maternal fish intake were significant for fine motor, problem-solving, and personal-social but not communication or gross motor. Conclusions: Fish consumption during pregnancy may be associated with a reduced risk of neurodevelopmental delay in 3-year-olds, particularly in the fine motor, problem-solving, and personal-social domains. Continued investigation after the age of 3 could further clarify the association.

Dietary intake of yogurt and cheese in children at age 1 year and sleep duration at age 1 and 3 years: the Japan Environment and Children's Study.

BACKGROUND: We previously reported that 1-year-old infants born to mothers who regularly consumed fermented food during pregnancy had a lower risk of sleep deprivation. However, it is not known if these positive effects are enhanced when infants themselves eat fermented foods or the long-term effects of such consumption. In this study, we examined the association between the frequency of fermented food intake during the child's weaning period and sleep deprivation at age 1 and 3 years. METHODS: This birth cohort study used data from a nationwide, government-funded study called the Japan Environment and Children's Study (JECS), covering 65,210 mother-child pairs. We examined the association between infants' consumption of fermented foods at 1 year of age and sleep deprivation at 1 and 3 years of age. RESULTS: There was no association between yogurt or cheese intake and sleep duration at age 1; at age 3, there was no group difference, although a trend test showed that yogurt intake at age 1 was significantly associated with sleep duration at age 3. There was also no association between the frequency of cheese intake and inadequate sleep duration at age 3. CONCLUSION: Frequency of children's yogurt and cheese intake at age 1 was not associated with sleep duration at age 1 or 3. However, a trend test showed a significant association between the frequency of yogurt intake at age 1 and sleep duration at age 3.

Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles.

OBJECTIVE: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. METHODS: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls. RESULTS: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling. CONCLUSION: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.

Association between maternal fermented food consumption and child sleep duration at the age of 3 years: the Japan Environment and Children's Study.

BACKGROUND: Using cohort data from the Japan Environment and Children's Study (JECS), we previously reported that the risk of sleep deprivation in 1-year-old children was reduced with a higher maternal intake of fermented foods, particularly miso. The present study, which evaluates children from the same cohort at 3 years of age, is a continuation of that work. METHODS: After applying exclusion criteria to 104,062 records in the JECS dataset, we evaluated 64,200 mother-child pairs in which the child was 3 years old. We examined the association of the dietary intake of fermented foods during pregnancy with child sleep duration < 10 h at the age of 3 years. RESULTS: Multivariable logistic regression analysis with the lowest quartile used as a reference revealed adjusted odds ratios (95% confidence intervals) for the second through fourth quartiles of 0.98 (0.90-1.06), 0.93 (0.85-1.01), and 0.85 (0.78-0.94) for cheese intake. CONCLUSIONS: The consumption of fermented foods during pregnancy is associated with reduced risk of sleep deprivation in 3-year-old children, albeit in a limited way.

Associations between Workers' Health and Working Conditions: Would the Physical and Mental Health of Nonregular Employees Improve If Their Income Was Adjusted?

Precarious employment can negatively affect health, but workers may be healthy if they earn enough income. This study uses equivalent disposable income and examines the interaction between income classes and employment types to clarify whether workers' health improves as the income classes rise. In Japan, nonstandard workers, called nonregular employees, have remained high since 2013. Therefore, using data from the national cross-sectional Comprehensive Survey of Living Conditions 2013, an official survey performed in Japan, we targeted a sample of employees aged 18 to 45 who graduated during the economic recession. Our final sample included 8282 employees (4444 males and 3838 females). The health (general and mental) status indicators used the dichotomized self-rated health and scores of the K6 questionnaires scored in the national survey. The association between income and health was almost proportional. Female workers tended to improve their health as their income class increased; however, this tendency was not observed in male workers, especially nonregular employees. Although the associations were weakened by added income information on the regression models, nonregular employees always showed inferior health to regular employees. The health status of nonregular employees, especially female nonregular employees, is statistically significantly lower than that of regular employees, even when the economic class is similar. In conclusion, improving low incomes for nonregular employees could improve health challenges, but income alone may not result in the same health status for regular and nonregular employees.

Qualitative and Quantitative Study on Components of Future Time Perspective and Their Association with Persistent Treatment for Type 2 Diabetes.

INTRODUCTION: Future time perspective (FTP) means the capacity to foresee, anticipate, and plan for future desired outcomes, and it contributes to persistent treatment for type 2 diabetes mellitus (T2DM). However, the components of FTP specific to T2DM patients have not been clarified. This study aimed to explore the components of FTP and to examine the associations between such components and persistent/impersistent diabetes treatment. METHODS: In this cross-sectional study, using qualitative and quantitative methods, 106 T2DM patients were enrolled by purposive sampling. The participants were interviewed in October and November 2018 by public health nurses in Koriyama City Public Health Center, Japan. In addition to the participants' status of treatment engagement (persistent/impersistent), their responses regarding reasons for persistent/impersistent treatment were collected and then summarized into nine subthemes, which were then merged into two main themes according to the presence or absence of FTP with a sense of T2DM ownership for analysis. RESULTS: The main theme, "presence of FTP with a sense of T2DM ownership," included subthemes such as "securing social independence," "planning on living a long and healthy life," "prioritizing avoiding being a burden on family and friends," "valuing improvement of diabetes," "avoiding tragic results," "optimistically viewing treatment as a form of self-development," and "improving mental health," whereas the main theme, "absence of FTP with a sense of T2DM ownership," included "lack of consciousness of disease" and "living a dissipated life." The association between the presence of FTP with a sense of T2DM ownership and persistent treatment for T2DM was found using Fisher's exact test (p < 0.001). CONCLUSION: Health care professionals should support T2DM patients in having an FTP with a sense of T2DM ownership and purpose in life instead of treatment goals when such patients mention their dissipated life or lack of insight into the disease.

Effectiveness of self-managed continuous monitoring for maintaining high-quality early essential newborn care compared to supervision visit in Lao PDR: a cluster randomised controlled trial.

BACKGROUND: Thousands of neonatal deaths are expected to be averted by introducing the Early Essential Newborn Care (EENC) in the Western Pacific Region. In Lao People's Democratic Republic (Lao PDR), the government adopted the EENC programme and expanded it to district hospitals. With the expansion, maintaining the quality of EENC has become difficult for the government. METHODS: A cluster randomised controlled trial with four strata based on province and history of EENC coaching was implemented to evaluate the effectiveness of self-managed continuous monitoring compared with supervisory visit in Lao PDR between 20 July 2017 and 2 April 2019. Health workers who were routinely involved in maternity care were recruited from 15 district hospitals in Huaphanh (HP) and Xiangkhouang (XK) provinces. The primary endpoint was the score on the determinants of EENC performance measured by the Theory of Planned Behaviour (TPB). Secondary endpoints were set as the knowledge and skill scores. A linear mixed-effects model was applied to test the effects of intervention over time on the endpoints. RESULTS: Among 198 recruited health workers, 46 (23.2%) did not complete the final evaluation. TPB scores were 180.9 [Standard Deviation: SD 38.6] and 182.5 [SD 37.7] at baseline and 192.3 [SD 30.1] and 192.3 [SD 28.4] at the final evaluation in the intervention and control groups, respectively. There was no significant difference in changes between the groups in the adjusted model (2.4, p = 0.650). Interviews with participants revealed that district hospitals in HP regularly conducted peer reviews and feedback meetings, while few hospitals did in XK. Accordingly, in stratified analyses, the TPB score in the intervention group significantly increased in HP (15.5, p = 0.017) but largely declined in XK (- 17.7, p = 0.047) compared to the control group after adjusting for covariates. Skill scores declined sharper in the intervention group in XK (- 8.78, p = 0.026), particularly in the practice of managing nonbreathing babies. CONCLUSIONS: The study indicates that self-managed continuous monitoring is effective in improving behaviour among district health workers; however, additional measures are necessary to support its proper implementation. To maintain resuscitation skills, repeated practice is necessary. TRIAL REGISTRATION: This trial was registered at UMIN Clinical Trials Registry on 15/6/2017. Registration number is UMIN000027794 .

Impact of the COVID-19 pandemic on working students: Results from the Labour Force Survey and the student lifestyle survey.

OBJECTIVE: The COVID-19 pandemic has caused devastating damage to employment globally, particularly among the non-standard workforce. The objective of this study was to identify the effects of the pandemic on the employment status and lives of working students in Japan. METHODS: The Labour Force Survey (January 2019 to May 2020) was used to examine changes in students' work situations. In addition, to investigate the economic and health conditions of university students during the pandemic, the Student Lifestyle Survey was conducted in late May 2020. This survey asked students at a national university in Tokyo about recent changes in their studies, work, and lives. RESULTS: The number of working students reported in the Labour Force Survey has declined sharply since March 2020, falling by 780,000 (46%) in April. According to a survey of university students' living conditions, 37% were concerned about living expenses and tuition fees, and a higher percentage of students who were aware of financial insecurity had poor self-rated health. CONCLUSION: Nearly half of working students have lost their jobs during the pandemic in Japan, which has affected their lives, studies, and health. There is a need to monitor the impact of economic insecurity on students' studies and health over time, and to expand the safety net for disadvantaged students.

Associations Between Social Support and Subjective Symptoms in Disaster-Stricken Ishinomaki, Japan.

OBJECTIVES: Natural disasters affect long-term health by directly disrupting or destroying health-care systems and social support. We examined the associations between social support and subjective symptoms (SS) among disaster victims living in their homes approximately 1-2 years after the Great East Japan Earthquake and tsunami on March 11, 2011, which devastated the northeastern Japan seaboard and far inland, focusing on Ishinomaki, Miyagi Prefecture. METHODS: The Health and Life Revival Council of Ishinomaki District conducted door-to-door household surveys between April 2012 and January 2013. Replies to 12 questions regarding social support, specifically emotional, informational, and instrumental, were investigated. SS prevalence was calculated as the proportion of those having any of 8 predetermined symptoms including back pain, neck stiffness, sleep difficulty, dizziness, heart palpitations, poor appetite, or stomachache. Logistic regression analysis by sex was used to obtain crude and adjusted odds ratios for the association between SS prevalence and forms of social support. RESULTS: From 4023 households, self-reported data on 2593 individuals from 1709 households were obtained. SS prevalence was 29.1%. Adjusted logistic regression analysis revealed that instrumental support with others and emotional support with personal and others were specific associated with SS in men and women, respectively. CONCLUSIONS: Our findings suggest that providing social support depending on needs is potentially effective in preventing SS in disaster areas.

Lysolipid Chain Length Switches Agonistic to Antagonistic G Protein-Coupled Receptor Modulation.

Activation of lysolipid-sensitive G protein-coupled receptors (GPCR) depends not only on lysolipid class but also on the length and degree of saturation of their respective hydrophobic tails. Positive regulation of these signaling networks caused by the lipid chain length specificity of upstream phospholipases is firmly established. Nonagonistic lysolipid homologues, featuring incompatible lipid tails, have been suggested to indirectly modulate GPCR signaling by delaying agonist catabolism. Nonetheless, recent results seem inconsistent with this hypothesis. Utilizing a simplified lysolipid-GPCR signaling assay based on the established lysophosphatidylglucoside-GPR55 signaling axis in primary sensory neurons, we demonstrate that short-chain ligand homologues directly modulate receptor activation via a potent competitive antagonistic activity. Considering the well-documented tissue-specific concentration of lysolipid homologues, we propose that endogenous lysolipids with insufficient chain length for stable receptor activation exert an antagonistic activity, effectively representing a negative control mechanism for GPCR-associated lysolipid signaling.