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ObjectiveThis study examined the relationship between job accommodations for workers with poor health and work functioning impairment during the COVID-19 pandemic.MethodsAn internet survey was conducted in December 2020. We included 24,429 subjects for analysis. One question was used to determine whether subjects needed job accommodations from their company to continue working in their current health condition. The odds ratios (ORs) of the necessity of job accommodations for sick workers associated with work functioning impairment were estimated using multilevel logistic regression analysis.ResultsThe OR of work functioning impairment among sick workers not receiving job accommodations was 5.75 (95% confidence interval (CI) 5.34-6.20, pConclusionsThis study suggests that providing job accommodations to workers with poor health may improve their work functioning impairment.

ObjectiveThis study investigated the association between attending work while experiencing fever or cold symptoms and workers’ socioeconomic background and company characteristics during the COVID-19 pandemic.MethodsA cross-sectional online survey was performed. Of a total of 33,302 participants, 3,676 workers who experienced fever or cold symptoms after April 2020 were included. The odds ratios (ORs) of attending work while sick associated with workers’ socioeconomic background and company characteristics were evaluated using a multilevel logistic model.ResultsThe OR of attending work while sick associated with a lack of policy prohibiting workers from working when ill was 2.75 (95%CI: 2.28–3.20, PConclusionThis study suggests that clear company policies on work and illness can be effective for preventing employees from attending work while sick.

Excessive accumulation of amyloid β-protein (Aβ) is one of the primary mechanisms that leads to neuronal death with phosphorylated tau in the pathogenesis of Alzheimer's disease (AD). Protofibrils, one of the high-molecular-weight Aβ oligomers (HMW-Aβo), are implicated to be important targets of disease modifying therapy of AD. We previously reported that phenolic compounds such as myricetin inhibit Aβ1-40, Aβ1-42, and α-synuclein aggregations, including their oligomerizations, which may exert protective effects against AD and Parkinson's disease. The purpose of this study was to clarify the detailed mechanism of the protective effect of myricetin against the neurotoxicity of HMW-Aβo in SH-SY5Y cells. To assess the effect of myricetin on HMW-Aβo-induced oxidative stress, we systematically examined the level of membrane oxidative damage by measuring cell membrane lipid peroxidation, membrane fluidity, and cell membrane potential, and the mitochondrial oxidative damage was evaluated by mitochondrial permeability transition (MPT), mitochondrial reactive oxygen species (ROS), and manganese-superoxide dismutase (Mn-SOD), and adenosine triphosphate (ATP) assay in SH-SY5Y cells. Myricetin has been found to increased cell viability by suppression of HMW-Aβo-induced membrane disruption in SH-SY5Y cells, as shown in reducing membrane phospholipid peroxidation and increasing membrane fluidity and membrane resistance. Myricetin has also been found to suppress HMW-Aβo-induced mitochondria dysfunction, as demonstrated in decreasing MPT, Mn-SOD, and ATP generation, raising mitochondrial membrane potential, and increasing mitochondrial-ROS generation. These results suggest that myricetin preventing HMW-Aβo-induced neurotoxicity through multiple antioxidant functions may be developed as a disease-modifying agent against AD.

Many factors are related to vaccination intentions. However, gender differences in the determinants of intention to get the coronavirus disease 2019 (COVID-19) vaccine have not been fully investigated. This study examined gender differences in the determinants of willingness to get the COVID-19 vaccine among the working-age population in Japan. We conducted a cross-sectional study of Japanese citizens aged 20–65 years using an online self-administered questionnaire in December 2020. Logistic regression analysis was performed. Among 27,036 participants (13,814 men and 13,222 women), the percentage who were willing to get the COVID-19 vaccine was lower among women than among men (33.0% vs. 41.8%). Age and education level showed a gender gap regarding the association with willingness to get the COVID-19 vaccine: men who were older or had a higher level of education were more willing to get the vaccine, whereas women aged 30–49 years and those with a higher level of education showed a relatively low willingness to get the vaccine. For both men and women, marriage, higher annual household income, underlying disease, current smoking, vaccination for influenza during the current season, and fear of COVID-19 transmission were linked to a higher likelihood of being willing to get the COVID-19 vaccine. These findings give important insight into identifying target groups in need of intervention regarding COVID-19 vaccination, especially among women. Providing education about COVID-19 and influenza vaccination in the workplace may be an effective strategy to increase COVID-19 vaccine uptake.

BackgroundThe COVID-19 pandemic has resulted in treatment interruption for chronic diseases. The scale of COVID-19 in Japan has varied greatly in terms of the scale of infection and the speed of spread depending on the region. This study aimed to examine the relationship between local infection level and treatment interruption among Japanese workers.MethodsCross-sectional internet survey was conducted from December 22 to 26, 2020. Of 33,302 participants, 9,510 (5,392 males and 4,118 females) who responded that they required regular treatment were included in the analysis. The infection level in each participant's prefecture of residence was assessed based on the incidence rate (per 1,000 population) and the number of people infected. Age-sex and multivariate adjusted odds ratios (ORs) of regional infection levels associated with treatment interruption were estimated by multilevel logistic models, nested by prefecture of residence. The multivariate model was adjusted for sex, age, marital status, equivalent household income, educational level, occupation, self-rated health status and anxiety.ResultsThe ORs of treatment interruption for the lowest and highest levels of infection in the region were 1.32 [95 % confidence interval (CI) were 1.09–1.59] for the overall morbidity rate (per 1,000) and 1.34 (95 % CI 1.10–1.63) for the overall number of people infected. Higher local infection levels were linked to a greater number of workers experiencing treatment interruption.ConclusionsHigher local infection levels were linked to more workers experiencing treatment interruption. Our results suggest that apart from individual characteristics such as socioeconomic and health status, treatment interruption during the pandemic is also subject to contextual effects related to regional infection levels. Preventing community spread of COVID-19 may thus protect individuals from indirect effects of the pandemic, such as treatment interruption.

The aim of the study was to evaluate the risk and threshold doses of lens opacity among residents exposed to low-dose radiation. Residents aged ≥45 years were recruited from a high natural background radiation (HNBR) area in Yangjiang City and a control area selected from nearby Enping City. Lens opacities (LOPs) were classified according to the Lens Opacities Classification System (LOCS) III system. Face-to-face interviews were conducted to collect information on lifestyles, migration and medical history. Life-time cumulative doses were estimated using gender, age, occupancy factors and environmental radiation doses received indoors and outdoors. Logistic regression analyses were conducted to estimate the dose response and determine thresholds. In the HNBR area, among 479 study participants, 101 (21.1%), 245(51.1%) and 23 cases (4.8%), respectively, of cortical, nuclear and posterior subcapsular (PSC) LOPs were found. In the control area, those types of LOPs were identified among 58 cases (12.6%), 206 cases (51.2%) and 6 cases (1.3%) of 462 examinees, respectively. Cumulative eye lens dose was estimated to be 189.5 ± 36.5 mGy in the HNBR area. Logistic analyses gave odds ratios at 100 mGy of 1.26 [95% confidence interval (CI) 1.00–1.60], 0.81 (95% CI 0.64–1.01) and 1.73 (95% CI 1.05–2.85) for cortical, nuclear and PSC LOPs, respectively. For cortical LOPs, a logistic analysis with a threshold dose gave a threshold estimate of 140 mGy (90% CI 110–160 mGy). The results indicated that population exposed to life-time, low-dose-rate environmental radiation was at an elevated risk of cortical and PSC LOPs. A statistically significant threshold dose was obtained for cortical LOPs and no threshold dose for PSC LOPs.

Objectives To determine the expression of hepatocyte growth factor (HGF) in RA biological fluids, the role of HGF in monocyte migration and the therapeutic effect of the c-Met inhibitor savolitinib in an arthritis model mice. Methods HGF/c-Met expression in serum, SF and synovial tissues (STs) obtained from RA patients and controls, as well as RA fibroblast-like synoviocytes (FLSs), was evaluated by ELISA and immunostaining. To determine the function of HGF in RA SF, we preincubated RA SF with a neutralizing anti-HGF antibody and measured the chemotactic ability of a human acute monocytic leukaemia cell line (THP-1). Additionally, examinations were conducted of SKG mice treated with savolitinib for 4 weeks. Results HGF levels in serum from RA patients were significantly higher than those in the controls and were decreased by drug treatment for 24 weeks. Additionally, the HGF level in SF from RA patients was higher than that in SF from OA patients. HGF and c-Met expression was also noted in RA STs. Stimulation of RA FLSs with TNF-α increased HGF/c-Met expression in a concentration-dependent manner, and c-Met signal inhibition suppressed production of fractalkine/CX3CL1 and macrophage inflammatory protein-1α/CCL3. When HGF was removed by immunoprecipitation, migration of THP-1 in RA SF was suppressed. In SKG mice, savolitinib significantly suppressed ankle bone destruction on µCT, with an associated reduction in the number of tartrate-resistant acid phosphatase-positive osteoclasts. Conclusion HGF produced by inflammation in synovium of RA patients activates monocyte migration to synovium and promotes bone destruction via a chemotactic effect and enhanced chemokine production.

ObjectiveWe examined whether teleworking preference and frequency were associated with work functioning impairment.MethodsThis online cross-sectional study was conducted using a self-administered questionnaire among 27,036 full-time Japanese workers. The Work Functioning Impairment Scale was used to measure work functioning impairment, and we performed multilevel logistic regression analysis.ResultsHigher odds ratios for work functioning impairment were observed among employees who preferred to telework compared with those who preferred working in the workplace. A similar trend was observed among employees who teleworked 4 or more days a week compared with those who almost never teleworked. When teleworking preference and frequency were adjusted, only teleworking preference was associated with work functioning impairment.ConclusionsA preference for teleworking was associated with work functioning impairment and one factor that increased the teleworking frequency.

ObjectivesThe purpose of this study was to investigate the relationships of workers being diagnosed with coronavirus disease 2019 (COVID-19) and being identified as close contacts of infected persons with unemployment in Japan.MethodsThis was a prospective cohort study using questionnaires about COVID-19 administered to Japanese workers. A baseline survey conducted on December 22–25, 2020, was used to determine history of being diagnosed with COVID-19 or being identified as a close contact of an infected person. Unemployment since the baseline survey was ascertained with a follow-up survey on February 18 and 19, 2021. The odds ratios of unemployment were estimated using a multilevel logistic model with adjusted covariates nested in prefecture of residence.ResultsWomen (n = 8,771) accounted for 44% of the total sample (n = 19,941), and the mean age was 48.0 years. In terms of unemployment because of negative reasons, the multivariate analysis showed that the odds ratio of unemployment associated with being diagnosed with COVID-19 was 2.18 (95% CI: 1.05–4.55) and that the odds ratio associated with being identified as a close contact was 0.93 (95% CI: 0.29–2.95).ConclusionsThere is an association between workers being diagnosed with COVID-19 and unemployment. Occupational health professionals should follow up closely with workers diagnosed with COVID-19 after they return to work to prevent them from becoming unemployed against their will.

ObjectivesTo prevent the spread of coronavirus disease 2019 (COVID-19) infection, it is necessary for each individual to adopt infection prevention behavior. We investigated the effect of infection control measures implemented in the workplace on personal infection prevention behavior.MethodsWe conducted a self-administered questionnaire survey through the Internet from December 22 to 25, 2020, during which period COVID-19 was spreading. Among respondents aged 20 to 65 years (n=27,036), a total of 21,915 workers were included in the analysis after excluding self-employed workers (n=2,202), workers in small/home offices (n=377), and agriculture, forestry, and fisheries workers (n=212), etc., whose personal infection prevention behavior was almost the same as infection control measures taken in the workplace.ResultsThe results showed that as the number of infection control measures in the workplace increased, implementation of infection prevention behavior by individuals also significantly increased. However, the relationship differed depending on the type of personal infection prevention behavior. Specifically, infection control measures against COVID-19 in the workplace may affect personal infection prevention behavior.ConclusionImplementation of infection control measures in the workplace appears to deepen personal understanding of infection prevention behaviors, and increases awareness of the importance of individual infection prevention behavior and its implementation by all individuals. These findings may be applicable not only to COVID-19 measures but also to responses to other emerging infections and seasonal influenza.

BackgroundThere are increasing concerns that prevention measures against coronavirus disease 2019 (COVID-19) such as social distancing and telework are leading to loneliness and poor lifestyle habits like increased alcohol consumption. The purpose of this study was to assess whether loneliness reported among workers during the COVID-19 pandemic is associated with changes in alcohol consumption.MethodsThe study comprised a cross-sectional, online survey of 27,036 workers between December 22 and 26, 2020. A questionnaire was used to assess loneliness, usual alcohol consumption and whether that consumption had changed. The odds ratios (ORs) were estimated by logistic regression analysis.ResultsA total of 2831 (10.5%) workers indicated they had increased alcohol consumption during the pandemic. Increased alcohol consumption was significantly associated with loneliness (OR=1.94, 95%CI 1.70–2.21). This association held true for those who indicated they were drinking two or more days per week (OR=1.98 95%CI 1.71–2.30) and those who drank less than one day per week (OR=1.51 95%CI 0.71–3.25). In contrast, there was no association between increased drinking and loneliness among those who indicated they hardly ever drank (OR=1.22 95%CI 0.55–2.72).ConclusionsAmong those with a drinking habit, increased alcohol consumption is associated with loneliness.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has been linked to a rise in loneliness. Loneliness is associated with sleep-related problems, which in turn can be a risk factor for various psychiatric disorders. However, it is unclear whether loneliness is linked to sleep-related problems during the pandemic. Here, we studied the association between loneliness and sleep-related problems during the COVID-19 pandemic in Japan.MethodsA total of 33,302 individuals who indicated they were employed were surveyed online. The survey responses of 27,036 participants were analyzed. Odds ratios (ORs) were estimated using univariate and multiple logistic regression analyses.ResultsOf those analyzed, 2,750 (10.2%) experienced feelings of loneliness. Further, sleep-related problems were significantly more common among those who felt lonely both in the short term (more than 3 days) and the long term (more than 3 months). The OR was much weaker after adjusting for factors related to interpersonal connections, such as family and friendships, than after adjusting for factors related to socioeconomic status.ConclusionsLoneliness may be a risk factor for sleep-related problems in the COVID-19 pandemic. Having connections with family and friends may have a moderating effect on the occurrence of sleep-related problems.

ObjectiveThis study investigated the effect of sick leave criteria on the association between long working hours and psychological distress.MethodsWe conducted a cross-sectional survey in December 2020, and 27,032 workers completed the questionnaire. First, after testing the interaction effect of overtime work hours and sick leave criteria on psychological distress, we conducted stratified analyses using sick leave criteria.ResultsA significant interaction effect was found. When we conducted stratified analyses, the odds ratios increased with longer working hours, both with and without sick leave criteria groups; however, the risk was greater in the without sick leave criteria group, compared with the criteria group.ConclusionWe revealed that working without sick leave criteria could strengthen the association between long working hours and psychological distress during the COVID-19 pandemic.Clinical significanceWorkers working without sick leave criteria had a significantly higher risk of psychological distress due to long working hours than those who worked with the criteria. Our findings contribute to preventing the deterioration of mental health during the COVID-19 pandemic.

ObjectiveMany companies in Japan have been increasingly interested in “health and productivity management (H&PM).” In terms of H&PM, we supposed that companies can enhance their employees’ perceived workplace health support (PWHS) by providing support for workers’ lively working and healthy living. This could then improve health-related QOL (HRQOL) by increasing PWHS. This study explored the relationship between PWHS and health-related quality of life (HRQOL).MethodsDuring the COVID-19 pandemic in December 2020, we conducted an Internet-based nationwide health survey of Japanese workers (CORoNaWork study). A database of 27,036 participants was created. The question regarding the intensity of PWHS was measured using a four-point Likert scale. We used a linear mixed model (LMM) to analyze the relationship between the intensity of PWHS and the four domains of CDC HRQOL-4 (self-rated health, number of poor physical health days, number of poor mental-health days, and activity limitation days during the past 30 days).ResultsIn the sex- and age-adjusted and multivariate models, the intensity of PWHS had a main effect on self-rated health and the three domains of unhealthy days (physical, mental, activity limitation). There was also a trend toward worse HRQOL scores as the PWHS decreased.ConclusionsThis study aimed to document the relationship between PWHS and HRQOL. We found that the higher the PWHS of Japanese workers, the higher their self-rated health and the lower their unhealthy days. Companies need to assess workers’ PWHS and HRQOL and promote H&PM. H&PM is also necessary to maintain and promote the health of workers during the COVID-19 pandemic.

BackgroundWe examined the association between socioeconomic and health status, and lifestyle and sickness presenteeism among Japanese workers during the COVID-19 epidemic.MethodsA cross-sectional study using an Internet-monitor survey was conducted in December, 2020 in Japan. Of 33,302 survey participants, we analyzed 27,036 participants (13,814 men and 13,222 women) who reported experience with sickness presenteeism.ResultsThe odds ratio (OR) of sickness presenteeism associated with unmarried versus married status was 1.15. Respective figures for other variables were 1.11 for manual laboring work compared to desk work; 1.79 and 2.29 for loss of employment at the time the pandemic began and continuation of unemployment compared to maintaining employment during the pandemic; and 3.34 for a feeling of financial instability compared to stability.ConclusionThe issue of sickness presenteeism has become more prominent under the COVID-19 epidemic.

BackgroundThe COVID-19 pandemic has dramatically transformed the work environment and work practices worldwide. Long-term infection control practices may increase the psychological stress on workers, and conversely, inadequate infection control practices at the working place may increase the fear of infection. This study aimed to determine the relationship between infection control practices at the workplace and employee mental health during the COVID-19 pandemic in Japan.MethodsThis study was conducted in December 2020 and February 2021. The participants had undergone a preliminary survey, which revealed that they were in good mental health. Their psychological distress was investigated via a second survey, and the factors associated with distress were studied using a logistic model.ResultsThe results of the second survey indicated that 15.1% of participants demonstrated psychological distress. This was associated with leave-of-absence instructions, instructions for shortening business hours, and requests to avoid the workplace in case of any symptoms.ConclusionThe study found that while some infection control practices reduce workers’ distress, others worsen it. Employers need to consider infection control practices as well as the worsening mental health of employees following a decrease in income caused by such measures. Follow-up studies may be necessary to clarify the long-term effects on workers’ mental health.

Purpose: There is limited information about the association between workplace psychosocial factors and general worker mental health status during the COVID-19 pandemic. In the present study, we examined how anxiety about being infected by COVID-19 in the workplace affected the association between job demands and psychological distress (PD).Method: A cross-sectional online survey was conducted in December 2020. The final analyzed sample was 27,036. The dependent variable of PD was assessed using the Kessler Psychological Distress Scale (K6). Job demands were assessed using the Job Content Questionnaire. Feelings of anxiety were assessed by participants' responses to the following question: “Do you feel anxiety about being infected by COVID-19 in the workplace?” We used a two-level regression adjusting for prefectural level: each individual-level variable at level 1 was nested into each prefecture at level 2, stratified by presence of anxiety.Results: A total of 50.5% of participants felt anxious about being infected by COVID-19 in the workplace. The interaction between anxiety and job demands was significant. Job demands were positively associated with PD. In the stratified analysis, the associations were stronger among employees who experienced anxiety about COVID-19 infection in the workplace than among those who did not.Conclusion: The association between job demands and PD may be strengthened by anxiety about COVID-19 infection in the workplace.

BackgroundThe current coronavirus (COVID-19) pandemic has had large impacts on society, including people practicing social distancing. This behavioral response has increased loneliness. Loneliness not only increases the risk of psychiatric disorders, but also affects occupational mental health. To avoid the negative effects of isolation, it is important to have social contact with other people, especially family members. Employment and economic instability caused by COVID-19 may have also affected family relationships. It is important to understand the association between family relationships and loneliness in workers under the pandemic.MethodsWe collected usable data from 27,036 Japanese workers who completed an online survey during the COVID-19 pandemic. Participants were asked how long they spend with members of their family during mealtimes or at home, and if they experienced loneliness; the latter was assessed by a single question. Other questions included whether participants lived with their spouse, or with someone in need of care. To estimate the odds ratios (ORs) of time with family associated with loneliness we used a multilevel logistic model nested in the prefecture of residence, with adjustments for age, sex, marital status, presence of a cohabitant requiring care, equivalent income, educational level, frequency of remote work, availability of someone for casual chat, smoking, drinking, time for leisure interests, and cumulative rates of COVID-19 in the prefecture.ResultsTen percent (2,750) of the 27,036 participants reported loneliness. The survey showed a significant negative correlation between time spent with family and loneliness (pppConclusionLoneliness under COVID-19 pandemic conditions was negatively associated with time spent with family members, with the converse result found for participants cohabiting with someone in need of care. These associations suggest the potential value of changes to working practices and interventions to combat loneliness.

We previously showed that the antiepileptic drug levetiracetam (LEV) inhibits microglial activation, but the mechanism remains unclear. The purpose of this study was to identify the target of LEV in microglial activity suppression. The mouse microglial BV-2 cell line, cultured in a ramified form, was pretreated with LEV and then treated with lipopolysaccharide (LPS). A comprehensive analysis of LEV targets was performed by cap analysis gene expression sequencing using BV-2 cells, indicating the transcription factors BATF, Nrf-2, FosL1 (Fra1), MAFF, and Spic as candidates. LPS increased AP-1 and Spic transcriptional activity, and LEV only suppressed AP-1 activity. FosL1, MAFF, and Spic mRNA levels were increased by LPS, and LEV only attenuated FosL1 mRNA expression, suggesting FosL1 as an LEV target. FosL1 protein levels were increased by LPS treatment and decreased by LEV pretreatment, similar to FosL1 mRNA levels. The FosL1 siRNA clearly suppressed the expression of TNFα and IL-1β. Pilocarpine-induced status epilepticus increased hippocampus FosL1 expression, along with inflammation. LEV treatment significantly suppressed FosL1 expression. Together, LEV reduces FosL1 expression and AP-1 activity in activated microglia, thereby suppressing neuroinflammation. LEV might be a candidate for the treatment of several neurological diseases involving microglial activation.

Background To combat coronavirus disease 2019 (COVID-19), many countries have used contact tracing apps, including Japan’s voluntary-use contact-confirming application (COCOA). The current study aimed to identify industry and workplace characteristics associated with the downloading of this COVID-19 contact tracing app. Methods This cross-sectional study of full-time workers used an online survey. Multiple logistic regression analysis was used to evaluate the associations of industry and workplace characteristics with contact tracing app use. Results Of the 27,036 participants, 25.1% had downloaded the COCOA. Workers in the public service (adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] 1.14–1.45) and information technology (aOR = 1.38, 95% CI 1.20–1.58) industries were more likely to use the app than were those in the manufacturing industry. In contrast, app usage was less common among workers in the retail and wholesale (aOR = 0.87, 95% CI 0.76–0.99) and food/beverage (aOR = 0.81, 95% CI 0.70–0.94) industries, but further adjustment for company size attenuated these associations. Workers at larger companies were more likely to use the app. Compared with permanent employees, the odds of using the app were higher for managers and civil servants but lower for those who were self-employed. Conclusions Downloading of COCOA among Japanese workers was insufficient; thus, the mitigating effect of COCOA on the COVID-19 pandemic is considered to be limited. One possible reason for the under-implementation of the contact tracing app in the retail and wholesale and food/beverage industries is small company size, as suggested by the fully adjusted model results. An awareness campaign should be conducted to promote the widespread use of the contact tracing app in these industries.

Estradiol has an important role in the brain, such as in neuronal development and protection, but estradiol levels in the human brain have not been well investigated. In this study, we measured the estradiol concentration in the cerebrospinal fluid (CSF) of infants to reveal the relationships between the estradiol concentrations in the serum and the CSF and further determined exosomal microRNAs in serum. Estradiol in the CSF was strongly correlated with serum estradiol and moderately correlated with miR-126-5p in the serum exosomes. This report is the first to determine the estradiol concentration in CSF from infants and showed that the levels of miR-126-5p as well as serum estradiol can be candidates to predict brain estrogen status.

Background: Metal exposures could possibly affect allergic responses in pregnant women, although no studies have yet shown a clear relationship between the two, and such exposures might also affect the development of allergic diseases in children. Methods: We investigated the relationship between metal concentrations in whole blood and immunoglobulin E (IgE; total and specific) in 14,408 pregnant women who participated in the Japan Environment and Children’s Study. The subjects submitted self-administered questionnaires, and blood samples were collected from them twice, specifically, during the first trimester and again during the second=third trimester. Concentrations of the metals Cd, Pb, Hg, Se, and Mn, as well as serum total and allergen-specific IgEs for egg white, house dust-mites (HDM), Japanese cedar pollen (JCP), animal dander, and moth, were measured. Allergen-specific IgE(s) were divided based on concentrations, This work was supported by the Ministry of the Environment, Japan., Supplementary data related to this article can be found at https://doi.org/10.2188/jea.JE20180098.

Purpose Dipeptidyl peptidase-4 inhibitors, including linagliptin, prevent inflammation. However, the in vitro effects of linagliptin are unclear. Moreover, although linagliptin inhibits lipopolysaccharide (LPS)-induced inflammation, the anti-inflammatory effects of linagliptin in this context are not concentration-dependent. In the absence of LPS-binding protein (LBP), the pro-inflammatory effects of LPS involve pathways other than the Toll-like receptor (TLR) 4 pathway. Here, we aimed to determine the anti-inflammatory mechanisms of linagliptin in an experimental model in which LBP was added to the medium. Methods Human U937 monocytes were cultured at 1 × 106 cells/mL in Roswell Park Memorial Institute medium and differentiated into macrophages using phorbol myristate acetate. All processes were carried out in medium containing 10% fetal bovine serum (FBS). After 48 hrs of culture, we replaced the medium and pretreated the cells with 100, 250, 500, or 2500 nM linagliptin for 1 hr. We exchanged the medium again, and the cells were treated with 1 ng/mL LPS with or without 100, 250, 500, or 2500 nM linagliptin. Interleukin (IL)-6 and LBP in the supernatant, nuclear factor (NF)-κB/p65 in the nucleus, and reactive oxygen species (ROS) in the cells, as important markers of the mechanism of inflammation induction by LPS, were measured using enzyme-linked immunosorbent assay kits. Results Linagliptin significantly prevented LPS-stimulated IL-6 production and intranuclear NF-κB/p65 levels in a concentration-dependent manner. LPS-induced intracellular ROS levels were significantly decreased by linagliptin at all concentrations. LBP levels were markedly higher in FBS-containing medium than in medium without FBS. However, LBP levels did not change following administration of linagliptin and/or LPS. Conclusion Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment in the context of LPS-induced pro-inflammatory responses. Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms.

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aβ species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aβ1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aβ1-42 were significantly greater than those of LMW-Aβ1-42. Therapeutic reduction of HMW-Aβ1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage.

ObjectivesThis study examined the relationship between interruption to routine medical care during the coronavirus disease 2019 pandemic and sickness presenteeism among workers in Japan.MethodsA cross-sectional study using data obtained from an internet monitor questionnaire was conducted. Interruption to medical care was defined based on the response “I have not been able to go to the hospital or receive treatment as scheduled.” The fraction of sickness presenteeism days in the past 30 days was employed as the primary outcome. A fractional logit model was used for analysis to treat bounded data.ResultsOf the 27,036 participants, 17,526 (65%) were workers who did not require routine medical care, 8,451 (31%) were using medical care as scheduled, and 1,059 (4%) experienced interrupted medical care. The adjusted odds ratio (aOR) of sickness presenteeism was significantly higher among workers who experienced interrupted medical care (3.44; 95% confidence interval [CI]: 3.04–3.89) than those who did not require routine medical care. In terms of symptoms, the highest aOR was observed among workers with mental health symptoms (aOR: 5.59, 95%CI: 5.04–6.20).ConclusionsThis study suggests the importance of continuing necessary treatment during a pandemic to prevent presenteeism.

ObjectivesTo examine the relationship between socioeconomic factors and unemployment among workers during COVID-19 pandemic in Japan.DesignA prospective cohort study, follow-up from December 22–25, 2020 through February 18–19, 2021.SettingThe panelists registered with an Internet survey companyParticipantsA cluster random sample of 33,087 workers with stratification by sex, job type, and region among Japan’s working populationMain outcomes and measuresUnemployment between December 2020 and February 2021ResultsAmong the 19,941 participants, 725 (3.6%) had experienced unemployment. Multivariate analysis showed that the significant high unemployment for women (compared to men); younger age (compared to older age); being married (spouse not working), bereaved or divorced, and unmarried (compared to married (spouse working)); annual household income less than 6 million yen, (compared to more than 10 million yen); junior high or high school, vocational school, junior college, or technical school (compared to graduate school); and temporary or contract employees, self-employed, agriculture, forestry, or fishing (compared to general employees).ConclusionsCOVID-19 appears to have created difficulties for the vulnerable groups. This suggests the need for employment and economic support for such individuals.Strengths and limitations of this studyUnder the pandemic of COVID-19, we found that unemployment was associated with socioeconomic factors such as age, sex, marriage, income, education and occupation.Our findings suggest that in the event of a major epidemic, resulting in unemployment among vulnerable segments of the labour market, regardless of whether workers themselves are infected.It was unclear why the participants had experienced unemploymentThis study was conducted as an Internet survey, so the generalizability of our results is limited.