Association between Dental Caries and Influenza Infection in Children: A Japanese Nationwide Population-Based Study

Dental caries is the most common chronic childhood disease. Recent studies have suggested that dental caries harbor respiratory infections in adults. We investigated the association between dental caries and influenza in children. In this study, 42,812 children aged 2.5 years, 38,540 children aged 5.5 years, and 34,124 children aged 10 years were included in the analysis from the Longitudinal Survey of Newborns in the 21st Century in Japan, which targeted all children born during a certain period in 2001. We used information on dental caries treated at hospitals and clinics in the past year as exposure and influenza as outcome during the observation periods (1.5-2.5, 4.5-5.5, and 9-10 years of age). We performed a log-binomial regression analysis, adjusting for potential confounders, and stratified analysis according to previous dental caries status. The presence of dental caries increased the incidence of influenza in all three target ages compared with the absence of dental caries. The incidence of influenza increased with the presence of current dental caries, regardless of the presence of past dental caries. These associations were observed irrespective of household income. Early detection and treatment of dental caries may reduce the risk of influenza in children

Longitudinal impact of the COVID-19 pandemic on the development of mental disorders in preadolescents and adolescents

Background　School closures and social distancing may have affected mental health among preadolescent and adolescent children, who are in a social developmental stage. Rates of anxiety, depression, and stress have been reported to have increased during the COVID-19 pandemic among teenagers worldwide. However, most studies have measured children's mental health in cross-sectional studies or short-term comparisons before and after lockdowns and school closures, and few studies have tracked the long-term effects on mental health among children and adolescents, despite the pandemic lasting more than 2 years. Methods　An interrupted time-series analysis was performed for longitudinal changes in the monthly number of new mental disorders (eating disorders, schizophrenia, mood disorders, and somatoform disorders). Using a nationwide multicenter electronic health records database in Japan, we analyzed data of patients aged 9 to 18 years from 45 facilities that provided complete data throughout the study period. The study period covered January 2017 to May 2021, defining a national school closure as an intervention event. We modeled the monthly new diagnoses of each mental disorder using a segmented Poisson regression model. Results　The number of new diagnoses throughout the study period was 362 for eating disorders, 1104 for schizophrenia, 926 for mood disorders, and 1836 for somatoform disorders. The slope of the regression line in monthly number of new diagnoses increased in the post-pandemic period for all targeted mental disorders (change in slope for eating disorders 1.05, 95% confidence interval [CI] 1.00-1.11; schizophrenia 1.04, 95% CI 1.01-1.07; mood disorders 1.04, 95% CI 1.01-1.07; and somatoform disorders 1.04 95% CI 1.02-1.07). The number of new diagnoses for schizophrenia and mood disorders increased early after school closure; while eating disorders showed an increasing trend several months later. Somatoform disorders showed a decreasing trend followed by an increasing trend. Time trends by sex and age also differed for each mental disorder. Conclusions　In the post-pandemic period, the number of new cases increased over time for eating disorders, schizophrenia, mood disorders, and somatoform disorders. The timing of increase and trends by sex and age differed for each mental disorder

Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity

M2a-subtype macrophage activation is known to be impaired in obesity, although the underlying mechanisms remain poorly understood. Herein, we demonstrate that, the IL-4/Irs2/Akt pathway is selectively impaired, along with decreased macrophage Irs2 expression, although IL-4/STAT6 pathway is maintained. Indeed, myeloid cell-specific Irs2-deficient mice show impairment of IL-4-induced M2a-subtype macrophage activation, as a result of stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex, resulting in insulin resistance under the HF diet condition. Moreover, the reduction of macrophage Irs2 expression is mediated by hyperinsulinemia via the insulin receptor (IR). In myeloid cell-specific IR-deficient mice, the IL-4/Irs2 pathway is preserved in the macrophages, which results in a reduced degree of insulin resistance, because of the lack of IR-mediated downregulation of Irs2. We conclude that downregulation of Irs2 in macrophages caused by hyperinsulinemia is responsible for systemic insulin resistance via impairment of M2a-subtype macrophage activation in obesity

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (>30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p<0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated

Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses

Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle

Experience with a nosocomial cluster of novel coronavirus infection and the cluster response algorithm

　The novel coronavirus disease (COVID-19) pandemic that began in 2019 is yet to end, as of the summer of 2022. During the pandemic, community-acquired infections spread easily to healthcare-associated facilities, resulting in COVID-19 clusters among high-risk individuals that have been difficult to contain. Our regional base hospital also experienced a nosocomial cluster of COVID-19 in October 2020 that took 30 days to contain and affected 9 hospital staff and 14 patients. Six patients died due to COVID-19, and six died due to COVID-19-related complications. Two patients were discharged alive. Patient characteristics included ① advanced age (79.0±8.1 years), ② dementia (64.3%), ③ low Prognostic Nutrition Index (31.1 ±7.9), ④ zinc deficiency (50.2±13.1μg/dL), ⑤ vitamin C deficiency (1.6±1.9μg/mL), ⑥ elevated urea nitrogen-to-creatinine ratio (27.4±23.5), ⑦ anticancer and immunosuppressive drug use (78.6%), and ⑧ malignancy (75.6%). This cluster had a very high mortality rate, but the viral spread was contained in a short period. Algorithmizing the cluster response was crucial to controlling this cluster. We report on our actual cluster response algorithm, as well as our strategy and response procedure during the pandemic