Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells.

Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible. DO 11.10 iTS cells were obtained from splenocytes of BALB/c DO 11.10 mice by stimulation with OVA peptide and antagonistic anti-CD80/CD86 mAbs. When DO 11.10 iTS or Foxp3- DO 11.10 iTS cells were stimulated with OVA, these cells produced IL-13, but not IL-4. DO 11.10 iTS cells decreased IL-4 and increased IL-13 production from OVA-stimulated naïve DO 11.10 splenocytes. When Foxp3+ DO 11.10 iTS cells were prepared, these cells significantly inhibited the production of IL-4 and IL-13 compared with freshly isolated Foxp3+ DO 11.10 T cells. Moreover, an increase in the population expressing OX40, ICOS, and 4-1BB suggested activation of Foxp3+ DO 11.10 iTS cells. Thus, blockade of CD80/CD86-CD28 co-stimulation during peptide antigen stimulation augments the inhibitory function of Foxp3+ regulatory T cells, and does not induce anergic Foxp3- conventional T cells. Peptide-specific Foxp3+ regulatory iTS cells could be useful for the treatment of allergic and autoimmune diseases without adverse effects.

The Prostaglandin D2 Receptor CRTH2 Contributes to Airway Hyperresponsiveness during Airway Inflammation Induced by Sensitization without an Adjuvant in Mice.

INTRODUCTION: Prostaglandin D2 (PGD2), which is produced mainly by Th2 cells and mast cells, promotes a type-2 immune response by activating Th2 cells, mast cells, eosinophils, and group 2 innate lymphoid cells (ILC2s) via its receptor, chemoattractant receptor-homologous molecules on Th2 cells (CRTH2). However, the role of CRTH2 in models of airway inflammation induced by sensitization without adjuvants, in which both IgE and mast cells may play major roles, remain unclear. METHODS: Wild-type (WT) and CRTH2-knockout (KO) mice were sensitized with ovalbumin (OVA) without an adjuvant and then challenged intranasally with OVA. Airway inflammation was assessed based on airway hyperresponsiveness (AHR), lung histology, number of leukocytes, and levels of type-2 cytokines in the bronchoalveolar lavage fluid (BALF). RESULTS: AHR was significantly reduced after OVA challenge in CRTH2 KO mice compared to WT mice. The number of eosinophils, levels of type-2 cytokines (IL-4, IL-5, and IL-13) in BALF, and IgE concentration in serum were decreased in CRTH2 KO mice compared to WT mice. However, lung histological changes were comparable between WT and CRTH2 KO mice. CONCLUSION: CRTH2 is responsible for the development of asthma responses in a mouse model of airway inflammation that features prominent involvement of both IgE and mast cells.

CD8+ T cell-mediated rejection of allogenic human-induced pluripotent stem cell-derived cardiomyocyte sheets in human PBMC-transferred NOG MHC double knockout mice.

BACKGROUND: Transplantation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) has emerged as a promising therapy to treat end-stage heart failure. However, the immunogenicity of hiPS-CMs in transplanted patients has not been fully elucidated. Thus, in vivo models are required to estimate immune responses against hiPS-CMs in transplant recipients. METHODS: We transferred human peripheral blood mononuclear cells (hPBMCs) into NOD/Shi-scid IL-2rgnull (NOG) MHC class I/II double knockout (NOG-ΔMHC) mice, which were reported to accept hPBMCs without xenogeneic-graft-versus-host disease (xeno-GVHD). Then, hiPS-CM sheets generated from the hiPS cell line 201B7 harboring a luciferase transgene were transplanted into the subcutaneous space of NOG-ΔMHC mice. Graft survival was monitored by bioluminescent images using a Xenogen In Vivo Imaging System. RESULTS: The human immune cells were engrafted for more than 3 months in NOG-ΔMHC mice without lethal xeno-GVHD. The hiPS-CMs expressed a moderate level of human leukocyte antigen (HLA)-class I, but not HLA-class II, molecules even after interferon-gamma (IFN-γ) stimulation. Consistently, the allogenic IFN-γ-treated hiPS-CMs induced weak CD8+ but not CD4+ T cell responses in vitro. hiPS-CM sheets disappeared approximately 17 to 24 days after transplantation in hPBMC-transferred NOG-ΔMHC mice, and CD8+ T cell depletion significantly prolonged graft survival, similar to what was observed following tacrolimus treatment. CONCLUSIONS: hiPS-CMs are less immunogenic in vitro but induce sufficient CD8+ T cell-mediated immune responses for graft rejection in vivo.

Association of COVID-19 preventive behavior and job-related stress with the sleep quality of healthcare workers one year into the COVID-19 outbreak: a Japanese cross-sectional survey.

BACKGROUND: This study aimed to evaluate the association of COVID-19 preventive behavior and job-related stress with sleep quality among healthcare workers (HCWs). We conducted a cross-sectional survey using a questionnaire at the National Center of Neurology and Psychiatry, Tokyo, Japan. METHODS: A total of 586 participants who completed the questionnaire were eligible for the study. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality. We examined the level of engagement between poor sleep and COVID-19-related infection preventive behaviors, such as avoiding closed spaces, crowded places, and close contact (three Cs), a distance of at least one meter from others, wearing a face mask regularly, washing hands regularly, and working remotely, as well as job-related stress in the work environment, exposure to patients, potential risk of infection, fear of infecting others, need for social confinement, and financial instability. We conducted a hierarchical logistic regression analysis to examine the relationship between poor sleep and COVID-19 preventive behavior, job-related stress, and other covariates, including age, sex, and the Kessler Psychological Distress Scale (K6), which was used to measure non-specific psychological distress. RESULTS: Poor sleep was observed in 223 (38.1%) participants. Adherence to COVID-19 preventive measures was relatively high: 84.1% of participants answered "always" for wearing a face mask regularly and 83.4% for washing hands regularly. In the multivariate logistic regression analysis, stress in the work environment (odds ratio [OR] = 2.09, 95% confidence interval [CI], 1.37-3.20; p < 0.001), financial instability (OR = 1.73, 95% CI, 1.12-2.67; p < 0.05), and low adherence to working remotely (OR = 1.65, 95% CI, 1.06-2.57; p < 0.05) were independently and significantly associated with poor sleep after controlling for the covariates. CONCLUSIONS: One year into the COVID-19 pandemic, the poor sleep rates of HCWs remained high. These results emphasize the need to protect HCWs from work environment stress and financial concerns.

The evaluation study for social cognition measures in Japan: Psychometric properties, relationships with social function, and recommendations.

AIM: Patients with schizophrenia can have significant subjective difficulties in social cognition, but few undergo testing or treatment for social cognition. The Social Cognition Psychometric Evaluation (SCOPE) study recommends six social cognitive measures; however, the reliability and validity of these measures in different cultural and linguistic areas has not been adequately examined. We examined the psychometric properties of nine social cognitive measures and the relationship to social function, with the aim of determining the level of recommendation for social cognitive measures in clinical practice in Japan. METHODS: For our test battery, an expert panel previously selected nine measures: the Bell Lysaker Emotion Recognition Task (BLERT); Facial Emotion Selection Test (FEST); Hinting Task (Hinting); Metaphor and Sarcasm Scenario Test (MSST); Intentionality Bias Task (IBT); Ambiguous Intentions and Hostility Questionnaire (AIHQ); Social Attribution Task-Multiple Choice (SAT-MC); SAT-MCII; and Biological Motion (BM) task. In total, 121 outpatients with schizophrenia and 70 healthy controls were included in the analysis, and the results were provided to an expert panel to determine the recommendations for each measure. The quantitative psychological indices of each measure were evaluated for practicality, tolerability, test-retest reliability, correlation with social function, and the incremental validity of social function. RESULTS: Hinting and FEST received the highest recommendations for use in screening, severity assessment, and longitudinal assessment, followed by BLERT, MSST AIHQ, SAT-MC, and SAT-MCII, with IBT and BM receiving the lowest recommendations. CONCLUSION: This study provides a uniform assessment tool that can be used in future international clinical trials for social cognitive impairment.

Association between health anxiety dimensions and preventive behaviors during the COVID-19 pandemic among Japanese healthcare workers.

Objective: Health anxiety (HA), defined as excessive worry about having a serious medical condition, may affect preventive behaviors during the coronavirus disease 2019 (COVID-19) pandemic. We examined the distinct role of two dimensions of HA-perceived likelihood (probability dimension) and awfulness of illness (awfulness dimension)-in self-protection, as reflected in preventive behaviors during the pandemic. Methods: Participants comprised 657 healthcare workers. Data were collected between February 24 and 26, 2021. The Short Health Anxiety Inventory determined the HA dimensions. Adherence to the government's recommendations for COVID-19 preventive behaviors was self-rated. An independent association between each HA dimension and participants' adherence to the recommendations was examined using multivariable regression. Results: Within the analyzed sample of 560 subjects, severe HA was observed in 9.1 %. The more the participants felt awful, the less frequently they engaged in the recommended preventive behaviors (adjusted odds ratio = 0.993, 95 % confidence interval: 0.989, 0.998, p = 0.003) regardless of their profession, working position, psychological distress, sleep disturbance, and current physical diseases. However, the probability dimension was not associated with their preventive behaviors. Conclusion: The awfulness dimension of HA could be a more sensitive marker of preventive behaviors than the probability dimension. Paying particular attention to the awfulness dimension may help optimize self-protection strategies during the COVID-19 pandemic. A two-dimensional understanding of HA may be useful for the maintenance of the healthcare system and public health as well as healthcare workers' own health.

The association between emotion malleability beliefs and severe psychological distress stratified by sex, age, and presence of any psychiatric disorders.

Background: Recent studies have shown an association between psychological distress and emotion malleability beliefs, meaning mindsets about whether one's emotions are fixed or changeable. However, most studies have not examined the association between these beliefs and sociodemographic factors. Methods: A nationwide cross-sectional Internet survey of residents of Japan aged 15-79 years was conducted using sampling weights for national estimates to investigate the association between emotion malleability beliefs and sociodemographic factors and between fixed beliefs and severe psychological distress (SPD). SPD was defined as a Kessler 6 Scale score of ≥13. Adjusted odds ratios for SPD were calculated considering potential confounders. Further analyses were stratified by sex, age and presence of any psychiatric disorder. Results: The analysis included 23,142 participants (female, 48.64%). Fixed beliefs were associated with female sex, age < 45 years, and presence of psychiatric disorders. These beliefs were associated with SPD, and additional analysis showed stronger associations with SPD among female respondents, respondents aged 45-59 years, and those aged ≥60 years. Conclusion: Results indicate that female sex, age < 45 years, and current mental disorders were associated with fixed emotion malleability beliefs. Associations between fixed emotion malleability beliefs and SPD were particularly strong among female respondents and people aged ≥45 years compared with the general population. Our study extends the association between emotion malleability beliefs and psychological health to the general population. Future studies should explore mechanisms underlying individual differences in emotion beliefs.

Individual prefrontal neurons contribute to sensory-to-motor information transformation by rotating reference frames during spatial working memory performance.

Performing working memory tasks correctly requires not only the temporary maintenance of information but also the visual-to-motor transformation of information. Although sustained delay-period activity is known to be a mechanism for temporarily maintaining information, the mechanism for information transformation is not well known. An analysis using a population of delay-period activities recorded from prefrontal neurons visualized a gradual change of maintained information from sensory to motor as the delay period progressed. However, the contributions of individual prefrontal neurons to this process are not known. In the present study, we used a version of the delayed-response task, in which monkeys needed to make a saccade 90o clockwise from a visual cue after a 3-s delay, and examined the temporal change in the preferred directions of delay-period activity during the delay period for individual neurons. One group of prefrontal neurons encoded the cue direction by a retinotopic reference frame and either maintained it throughout the delay period or rotated it 90o counterclockwise to adjust visual information to saccade information, whereas other groups of neurons encoded the cue direction by a saccade-based reference frame and rotated it 90o clockwise. The results indicate that visual-to-motor information transformation is achieved by manipulating the reference frame to adjust visual coordinates to motor coordinates.

Feasibility of a wrist-worn wearable device for estimating mental health status in patients with mental illness.

Object: Real-world data from wearable devices has the potential to understand mental health status in everyday life. We aimed to investigate the feasibility of estimating mental health status using a wrist-worn wearable device (Fitbit Sense) that measures movement using a 3D accelerometer and optical pulse photoplethysmography (PPG). Methods: Participants were 110 patients with mental illnesses from different diagnostic groups. The study was undertaken between 1 October 2020 and 31 March 2021. Participants wore a Fitbit Sense on their wrist and also completed the State-Trait Anxiety Inventory (STAI), Positive and Negative Affect Schedule (PANAS), and EuroQol 5 dimensions 5-level (EQ-5D-5L) during the study period. To determine heart rate (HR) variability (HRV), we calculated the sdnn (standard deviation of the normal-to-normal interval), coefficient of variation of R-R intervals, and mean HR separately for each sleep stage and the daytime. The association between mental health status and HR and HRV was analyzed. Results: The following significant correlations were found in the wake after sleep onset stage within 3 days of mental health status assessment: sdnn, HR and STAI scores, HR and PANAS scores, HR and EQ-5D-5L scores. The association between mental health status and HR and HRV was stronger the closer the temporal distance between mental health status assessment and HR measurement. Conclusion: A wrist-worn wearable device that measures PPG signals was feasible for use with patients with mental illness. Resting state HR and HRV could be used as an objective assessment of mental health status within a few days of measurement.

Subgingival titanium wire implantation induces weak inflammatory responses but does not promote substantial T cell activation.

Titanium is a biocompatible material commonly used for dental treatments. However, the detailed mechanism underlying the weak biological activity of titanium has not been elucidated. We investigated both the inflammatory responses and T cell activation induced by solid titanium in the gingiva in mice. Both titanium and nickel wire implantation promoted neutrophil infiltration into the gingiva on day 2. Nickel, but not titanium, wire implantation enhanced proinflammatory cytokine expression and dendritic cell activity in gingival tissue by day 2. Nickel wire implantation enhanced the activity of T cells in draining lymph nodes on day 5. Moreover, T cell and neutrophil infiltration and elevated proinflammatory cytokine expression in the gingival tissue were still observed on day 5. However, no such augmented biological responses were observed after titanium wire implantation. These findings suggest that, unlike nickel, solid titanium does not induce sufficient inflammatory responses leading to T cell activation in gingival tissue.

Anti-influenza Activity of Povidone-Iodine-Integrated Materials.

Personal protective equipment (PPE), including medical masks, should be worn for preventing the transmission of respiratory pathogens via infective droplets and aerosols. In medical masks, the key layer is the filter layer, and the melt-blown nonwoven fabric (NWF) is the most used fabric. However, the NWF filter layer cannot kill or inactivate the pathogens spread via droplets and aerosols. Povidone-iodine (PVP-I) has been used as an antiseptic solution given its potent broad-spectrum activity against pathogens. To develop PPE (e.g., medical masks) with anti-pathogenic activity, we integrated PVP-I into nylon-66 NWF. We then evaluated its antiviral activity against influenza A viruses by examining the viability of Madin-Darby canine kidney (MDCK) cells after inoculation with the virus strains exposed to the PVP-I-integrated nylon-66 NWF. The PVP-I nylon-66 NWF protected the MDCK cells from viral infection in a PVP-I concentration-dependent manner. Subsequently, we found to integrate PVP-I into nylon-66 and polyurethane materials among various materials. These PVP-I materials were also effective against influenza virus infection, and treatment with PVP-I nylon-66 NWF showed the highest cell survival among all the tested materials. PVP-I showed anti-influenza A virus activity when used in conjunction with PPE materials. Moreover, nylon-66 NWF integrated with PVP-I was found to be the best material to ensure anti-influenza activity. Therefore, PVP-I-integrated masks could have the potential to inhibit respiratory virus infection. Our results provide new information for developing multi-functional PPEs with anti-viral activity by integrating them with PVP-I to prevent the potential transmission of respiratory viruses.

Underlying medical conditions and anti-SARS-CoV-2 spike IgG antibody titers after two doses of BNT162b2 vaccination: A cross-sectional study.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

The association between experience of COVID-19-related discrimination and psychological distress among healthcare workers for six national medical research centers in Japan.

BACKGROUND: Discrimination is an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan. METHODS: This cross-sectional study conducted a health survey among 5703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥ 13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified factors associated with discrimination. RESULTS: Of the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (adjusted odds ratio [AOR] = 1.41, 95% confidence interval [CI] = 1.28-1.55), had high vs. low viral exposure (AOR = 2.31, 95% CI = 1.81-2.93), and worked for 11 or more hours/day vs. 8 or less hours/day (AOR = 1.42, 95% CI = 1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The AOR (95% CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. In the stratified analysis by sociodemographic and job-related factors, all the interactions did not reach statistical significance (p for interaction > 0.20). CONCLUSION: Experience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.

Association of COVID-19-related discrimination with subsequent depression and suicidal ideation in healthcare workers.

Previous cross-sectional studies showed that COVID-19-related discrimination against healthcare workers was linked to depression. However, no study has examined the longitudinal association that allows causal interpretations. This prospective cohort study aimed to examine whether COVID-19-related discrimination at baseline is associated with depression and suicidal ideation several months later. Data were collected from October 2020 to July 2021. Multivariable logistic regression was performed. Fixed effects models were used to control for the effect of hospitals (Level 2 variable). Adjustments also included age, sex, living alone, alcohol consumption, exercise, BMI, working hours, comorbidity, and frontline worker status (Level 1 variables). Multiple sensitivity analyses were conducted to examine if the results substantially changed and were robust to unmeasured confounding. Multiple imputation for missing data was conducted via chained equations. As the final sample, 2862 healthcare workers without depression at baseline were studied. A total of 269 individuals (9.4%) experienced COVID-19-related discrimination. Depression was suggested in 205 participants (7.2%), and suicidal ideation in 108 participants (3.8%). In the adjusted models, COVID-19-related discrimination was significantly associated with subsequent depression (OR = 2.18, 95% CI = 1.39 to 2.90) and suicidal ideation (OR = 2.07, 95% CI = 1.22 to 3.50). Multiple sensitivity analyses verified the results. COVID-19-related discrimination results in depression and suicidal ideation in healthcare workers. Interventions to prevent such discrimination against healthcare workers, e.g., anti-discrimination campaigns, are crucial during the COVID-19 pandemic.

An IL-12-Based Nanocytokine Safely Potentiates Anticancer Immunity through Spatiotemporal Control of Inflammation to Eradicate Advanced Cold Tumors.

Treatment of immunologically cold tumors is a major challenge for immune checkpoint inhibitors (ICIs). Interleukin 12 (IL-12) can invigorate ICIs against cold tumors by establishing a robust antitumor immunity. However, its toxicity and systemic induction of counteracting immunosuppressive signals have hindered translation. Here, IL-12 activity is spatiotemporally controlled for safely boosting efficacy without the stimulation of interfering immune responses by generating a nanocytokine that remains inactive at physiological pH, but unleashes its full activity at acidic tumor pH. The IL-12-based nanocytokine (Nano-IL-12) accumulate and release IL-12 in tumor tissues, eliciting localized antitumoral inflammation, while preventing systemic immune response, counteractive immune reactions, and adverse toxicities even after repeated intravenous administration. The Nano-IL-12-mediated spatiotemporal control of inflammation prompt superior anticancer efficacy, and synergize with ICIs to profoundly inflame the tumor microenvironment and completely eradicate ICI-resistant primary and metastatic tumors. The strategy could be a promising approach toward safer and more effective immunotherapies.

IL-33 deficiency suppresses alveolar bone loss in a ligature-induced periodontitis model.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been studied primarily in the context of type 2 immune responses. Recent reports suggest that IL-33 also enhances the func- tions of various immune cells and contributes to the development of different inflammatory diseas- es. Interestingly, IL-33 and its receptor ST2 axis exerted either inhibitory or promotional effects on alveolar bone loss in various periodontitis models. Using a mouse model of ligature-induced periodontitis, we found that the levels of mRNAs encoding IL-33 and other inflammatory cyto- kines (IL-1α, IL-1ß, IL-6, and TNFα) were augmented in gingival tissues of wild-type (WT) mice, and that the alveolar bone loss amount was lower in IL-33-deficient than WT mice. The numbers and proportions of IFN-γ-producing CD8+ T and regulatory T cells were decreased while those of Th17 cells were increased in the draining lymph nodes of IL-33-deficient mice compared to WT mice. Additionally, the level of RNA encoding an osteoclastogenic molecule, i.e., receptor activa- tor of nuclear factor kappa-B ligand (RANKL), in ligated gingival tissue was higher in IL-33-defi- cient than WT mice. These results suggest that IL-33 is involved in alveolar bone loss in the ligature-induced periodontitis model, although IL-33 may inhibit osteoclast differentiation.

Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.

COVID-19-related discrimination, PTSD symptoms, and psychological distress in healthcare workers.

To date, little effort has been made to examine if frontline workers who deal with COVID-19 patients are more likely to experience discrimination than second-line workers. Also, little information has appeared on how COVID-19-related discrimination affects PTSD symptoms in healthcare workers. We aimed to examine the association between COVID-19-related discrimination and frontline worker status. We further aimed to examine how COVID-19-related discrimination was associated with PTSD symptoms and psychological distress. We studied 647 healthcare workers. For the association between COVID-19-related discrimination and frontline worker status, we conducted multivariable logistic regression adjusting for age, sex and living alone. For the association of COVID-19-related discrimination with PTSD symptoms and psychological distress, we performed multivariable regression using hierarchical adjustments for age, sex, living alone, alcohol consumption, exercise and frontline worker status. Bias-corrected and accelerated bootstrap confidence intervals (CIs) were used. A total of 136 individuals worked on the frontline and the largest group were nurses (n = 81, 59.6%). Frontline workers had increased odds of COVID-19-related discrimination compared with second-line workers (odds ratio = 2.60, 95% CI = 1.37-4.96). COVID-19-related discrimination was associated with PTSD symptoms and psychological distress even at the highest level of adjustment (ß = 0.67, 95% CI = 0.10-1.23; ß = 2.43, 95% CI = 0.91-3.95, respectively). Frontline workers are more likely to experience COVID-19-related discrimination than second-line workers. Such discrimination may result in PTSD symptoms and psychological distress. Interventions to prevent COVID-19-related discrimination against healthcare workers, for example anti-discrimination campaigns, are important.