A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. METHODS: This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 µg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. RESULTS: There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. CONCLUSIONS: A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. TRIAL REGISTRATION: NCT number: NCT04354480; Clinical Registry number: CR108768.

Impact of COVID-19 pandemic on physical health amongst children: Difference-in-differences analyses of nationwide school health checkup database.

INTRODUCTION: The COVID-19 pandemic posed tremendous challenges for children. However, the long-term effects of the pandemic on various aspects of physical health at a national level remain unclear. METHODS: In this retrospective cohort study, we analysed data from nationwide health checkup records amongst children aged 7-15 years. The dataset comprised 3 544 146 records from 393 794 individuals who graduated from junior high school during fiscal years 2007 to 2022. Difference-in-differences (DID) analyses with multiple time periods were used to examine the impact of COVID-19 on physical health outcomes. RESULTS: Compared with the pre-pandemic period, the COVID-19 pandemic was associated with excess increases in obesity for boys and girls, persisting over the 3 years (+0.42%; [95% CI, 0.23-0.61]). Also, it was associated with excess increases in underweight (+0.28% [0.25-0.32]) and poor visual acuity amongst boys in the 3rd year (+1.80% [1.30-2.30]). There were excess reductions in dental caries (-1.48% [-2.01 to -0.95]), glucosuria (-0.55 [-0.88 to -0.23]) and hematuria (-0.43% [-0.73 to -0.13]) during the 3rd year of the pandemic. CONCLUSIONS: These findings underscore the multifaceted impact of the pandemic on various health indicators for school-aged children. This information could be valuable for public health policy and paediatric healthcare planning in the post-pandemic era.

Nationwide epidemiology and health resource use among children with COVID-19 in Japan.

BACKGROUND: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. METHODS: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. RESULTS: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). CONCLUSIONS: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness.

Structural and organizational determinants of the capacity for COVID-19 testing and diagnoses in children: Insights from the 2009 influenza and COVID-19 pandemics.

BACKGROUND: This study explored factors associated with testing and diagnoses for children with COVID-19 at the hospital level and investigated whether the capacity of testing and diagnoses during the 2009 influenza pandemic was associated with that during COVID-19 pandemic. METHODS: In this observational study, we analyzed data obtained from the Japan Medical Data Center database, comprising 4906 medical facilities and 1.7 million infectious disease-related visits among children aged <20 years in 2020-2021. Multivariable generalized linear models were used to explore determinants of testing and diagnoses capacity for COVID-19 and investigate the association between the capacity during the 2009 influenza and COVID-19 pandemics. RESULTS: Public hospitals (adjusted incidence rate ratio [aIRR], 1.52; 95%CI, 1.26-1.82) and university hospitals (aIRR, 1.44; 95%CI, 1.14-1.80) were more likely to perform testing for COVID-19 among children, compared to clinics. The highest testing rate was observed in the department of internal medicine (aIRR, 1.64; 95%CI, 1.32-2.04), followed by pediatrics (aIRR, 1.40; 95%CI, 1.10-1.78) and otolaryngology (aIRR, 1.21; 95%CI, 0.89-1.64). Cubic spline models demonstrated the dose-response relationships between testing rate for influenza in 2009 and testing rates for COVID-19. Compared to the medical facilities in the lowest quartile of testing rate for influenza in 2009, those in the highest quartile were more likely to perform testing for COVID-19 (aIRR, 1.62; 95%CI, 1.43-1.83). CONCLUSIONS: Our study provides insights into the capacity of testing and diagnoses for children, highlighting the dose-response relationship between the 2009 influenza and COVID-19 pandemics, which could be valuable in preparing healthcare systems for future pandemics.

Infection prevention measures and its determinants in childcare facilities during the COVID-19 pandemic: A nationwide survey (2022-2023).

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic presented an unprecedented challenge to societies, necessitating adaptations in infection prevention measures. While there is ample data on infection prevention practices in workplace and healthcare settings, comprehensive data specific to childcare facilities has been lacking. METHODS: We conducted a nationwide web-based survey capturing responses from various childcare facilities (N = 549). This aimed to understand the adaptation in infection prevention measures between fiscal years 2022 and 2023, the status of events and activities, and the factors influencing decision-making related to infection prevention. RESULTS: From 2022 to 2023, most childcare facilities reduced infection prevention practices like mandatory mask-wearing (46.9 %-7.5 %) and eating without conversing (56.5 %-7.4 %), whereas they continued high levels of hand sanitization and checking child's health condition before attendance. The frequency of events and activities (e.g., athletic meets, field trips) increased, with many being held without restrictions. Surprisingly, 62.8 % of facilities used items not recommended for infection prevention. The influence of local government guidelines (risk ratio, 0.69; 95%CI, 0.53-0.90) and the input from junior teachers (risk ratio, 0.85; 95%CI, 0.72-0.99) were associated with reduced risk of using inappropriate items. Furthermore, childcare facilities emphasized the need to collaborate with public health and medical professionals for more accurate and efficient decision-making during pandemics. CONCLUSIONS: The survey provides insights into the evolving practices of Japanese childcare facilities during the COVID-19 pandemic. It underscores the importance of refining information sources, enhancing decision-making processes, and fostering collaboration with the medical community for future pandemics and natural disasters.

Clinical Practice Patterns, Health Resource Use and Risk Factors for Severe Conditions Among Children Hospitalized With COVID-19 in Japan.

BACKGROUND: The trends in clinical practice patterns and health resource use, as well as risk factors for severe conditions among children hospitalized with coronavirus disease-2019 (COVID-19), remain unclear. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 9876 children hospitalized with COVID-19 during 2020-2022 using the Medical Data Vision database in Japan. We investigated trends in patient characteristics, health resource use, treatment patterns and laboratory data. Additionally, log-binomial regression models were used to investigate the risk factors associated with severe COVID-19 among pediatric inpatients with COVID-19. RESULTS: We observed decreasing trends in the lengths of hospital stays, healthcare costs, computed tomography use, and antibiotic use, and increasing trends in treatment with intravenous hydration and use of antipyretics, antiepileptics, antiemetics and antivirals from the first wave to the seventh wave of COVID-19 pandemic. During the 3-year period, the risk of severe COVID-19 was almost stable at 3%. Risk factors associated with severe COVID-19 were children less than 1 year old [risk ratio (RR): 1.69; 95% confidence interval (CI): 1.02-2.78], the number of complex chronic diseases (RR for 1 disease: 4.49; 95% CI: 2.76-7.32; RR for 2 or more diseases: 10.2; 95% CI: 5.19-20.3) and asthma (RR: 1.84; 95% CI: 1.06-3.20). CONCLUSIONS: Our study observed the changes in practice patterns and health resource use for children hospitalized with COVID-19 and identified risk factors associated with severe COVID-19. These findings indicate the importance of vigilant monitoring and tailored treatment strategies in children with these risk factors.

Clinical Practice Patterns and Risk Factors for Severe Conditions in Pediatric Hospitalizations With Respiratory Syncytial Virus in Japan: A Nationwide Analyses (2018-2022).

BACKGROUND: Respiratory syncytial virus (RSV) represents a global health challenge, especially among younger children. While the disease burden in Japan has been preliminarily quantified, there remains a lack of comprehensive understanding regarding treatment patterns and the influence of known risk factors at a national scale. MATERIALS AND METHODS: We conducted a retrospective cohort study consisting of 50,482 children under 5 years hospitalized with RSV infections during 2018-2022 using the Medical Data Vision database. We investigated trends in patient characteristics, health resource use, treatment patterns, and laboratory data. Additionally, multivariable modified Poisson regression models were used to investigate the risk factors associated with severe conditions. RESULTS: We observed an increasing trend in the inpatient healthcare costs and decreasing trends in the use of antibiotics, bronchodilators, systemic corticosteroids and other symptomatic medications from 2018 to 2022. Risk factors associated with severe RSV infections were children less than 1 year (risk ratio, 2.90; 95% CI: 2.53-3.32) and the number of complex chronic diseases (risk ratio for 1 disease, 2.68; 95% CI: 2.34-3.06: risk ratio for 2 or more diseases, 6.91; 95% CI: 5.81-8.21). Annual inpatient healthcare costs for RSV infections were estimated at 11-14 billion Japanese Yen for younger children. CONCLUSIONS: Our study observed the changes in practice patterns and health resource use for children hospitalized with RSV infections and identified risk factors associated with severe conditions. These findings provide insights for policymakers and clinicians aiming to devise strategies for further improving clinical practices, including newly developed vaccines and single-dose long-acting monoclonal antibodies.

The effect of poverty on the relationship between household education levels and obesity in U.S. children and adolescents: an observational study.

Background: Although ample evidence has shown the link between childhood obesity and socioeconomic status including family income and household education levels, the mediating role of poverty in the association between household education levels and childhood obesity is unclear. This study aimed to quantify the extent to which family poverty levels contribute to the association between household education levels and obesity among US children and adolescents. Methods: This cohort study used the nationally representative data of 21,754 US children and adolescents aged 6-17 years (National Health and Nutrition Examination Survey 1999-2018). We applied mediation analysis of the association between household education levels (less than high school, high school, and college or above) and obesity mediated through poverty (≤138% vs. >138% federal poverty level), adjusting for demographic characteristics of household head and their offspring. Obesity was defined as age- and sex-specific body mass index in the 95th percentile or greater using the 2000 Centers for Disease Control and Prevention growth charts. Findings: Among 21,754 children and adolescents (weighted N = 43,544,684; mean age, 11.6 years; female, 49%), 9720 (weighted percentage, 33.0%) were classified as living in poverty and 4671 (weighted percentage, 19.1%) met the criteria for obesity. Low household education level (less than high school) showed increased risks of poverty (adjusted relative risk [95% CI], 5.82 [4.90-6.91]) and obesity (adjusted relative risk [95% CI], 1.94 [1.68-2.25]) compared to high household education level (college or above). We also quantified that poverty mediated 18.9% of the association between household education levels and obesity among children and adolescents. The mediation effect was consistently observed across age, gender, and race/ethnicity. Interpretation: Poverty mediated the association between the low educational status of household heads and their offspring's obesity. Our findings highlight the importance of reducing obesity risk among the low-income population to minimize the burden of intergenerational health disparities due to socioeconomic status. Funding: Japan Society for the Promotion of Sciences (22K17392).

Impacts of routine varicella vaccination program and COVID-19 pandemic on varicella and herpes zoster incidence and health resource use among children in Japan.

PURPOSE: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. RESULTS: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. CONCLUSIONS: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.

Nationwide epidemiology and clinical practice patterns of pediatric urinary tract infections: application of multivariate time-series clustering.

BACKGROUND: The nationwide epidemiology and clinical practice patterns for younger children hospitalized with urinary tract infections (UTIs) were unclear. METHODS: We conducted a retrospective observational study consisting of 32,653 children aged < 36 months who were hospitalized with UTIs from 856 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. We investigated the epidemiology of UTIs and changes in clinical practice patterns (e.g., antibiotic use) over 8 years. A machine learning algorithm of multivariate time-series clustering with dynamic time warping was used to classify the hospitals based on antibiotic use for UTIs. RESULTS: We observed marked male predominance among children aged < 6 months, slight female predominance among children aged > 12 months, and summer seasonality among children hospitalized with UTIs. Most physicians selected intravenous second- or third-generation cephalosporins as the empiric therapy for treating UTIs, which was switched to oral antibiotics during hospitalizations for 80% of inpatients. Whereas total antibiotic use was constant over the 8 years, broad-spectrum antibiotic use decreased gradually from 5.4 in 2011 to 2.5 days of therapy per 100 patient-days in 2018. The time-series clustering distinctively classified 5 clusters of hospitals based on antibiotic use patterns and identified hospital clusters that preferred to use broad-spectrum antibiotics (e.g., antipseudomonal penicillin and carbapenem). CONCLUSIONS: Our study provided novel insight into the epidemiology and practice patterns for pediatric UTIs. Time-series clustering can be useful to identify the hospitals with aberrant practice patterns to further promote antimicrobial stewardship. A higher resolution version of the Graphical abstract is available as Supplementary information.

Trends in Influenza and Related Health Resource Use During 2005-2021 Among Children in Japan.

BACKGROUND: To determine the epidemiological trends in pediatric influenza and changes in healthcare resource use from 2005 to 2021 using nationally representative outpatient database in Japan. METHODS: We conducted a retrospective cohort study consisting of 3.5 million children with 177 million person-months during 2005-2021 using Japan Medical Data Center claims database in Japan. We investigated trends in incidence rates of influenza and changes in healthcare resource use (eg, use of antivirals) over 17 years. Generalized estimation equations were used to investigate the impact of the 2009 influenza pandemic and the coronaviral disease 2019 (COVID-19) pandemic on incidence rates of influenza and related healthcare utilization. RESULTS: Annual incidence rates of influenza were estimated at 55 cases per 1000 person-years with a 93% relative increase [95% confidence interval (CI): 80%-107%] during the 2009 influenza pandemic and a 99.4% relative reduction (95% CI: 99.3%-99.4%) during the COVID-19 pandemic. Similar patterns were observed for health resource use, total healthcare costs, admission rates and antiviral agent use. Approximately 80% of children with influenza received prescriptions for antivirals. The most prescribed antivirals were oseltamivir, but we observed a temporal increase in zanamivir use during 2007-2009, an increasing trend in laminamivir use during 2010-2017, a temporal increase in baloxavir use in 2018. Symptomatic medications with serious side effects (codeine, salicylate, sedative antihistamine) showed decreasing trends over the study period. CONCLUSIONS: Influenza incidence and healthcare resource use were largely affected by the 2009 influenza pandemic and the COVID-19 pandemic. Our study indicates improvement of quality in healthcare delivered to children.

Effects of Dexmedetomidine on Brain and Inflammatory Outcomes In Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Dexmedetomidine use decreases adverse neurocognitive outcomes in adults undergoing cardiovascular surgery, but its effect has been unclear in children with congenital heart disease. METHODS: The authors conducted a systematic review using the PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that compared intravenous dexmedetomidine with normal saline during pediatric cardiac surgery under anesthesia. Published randomized controlled trials that evaluated children aged <18 years who underwent congenital heart surgery were included. Nonrandomized trials, observational studies, case series and case reports, editorials, reviews, and conference papers were excluded. The quality of the included studies was assessed using the Cochrane revised tool for assessing risk-of-bias in randomized trials. Meta-analysis was performed to estimate the effects of intravenous dexmedetomidine on brain markers (neuron-specific enolase [NSE], S-100ß protein) and inflammatory markers (interleukin-6, tumor necrosis factor [TNF]-α, nuclear factor kappa-B [NF-κB]) during and after cardiac surgery, using random-effect models for standardized mean difference (SMD). RESULTS: Seven RCTs involving 579 children were eligible for the following meta-analyses. Most children underwent cardiac surgery for atrial or ventricular septum defects. Pooled analyses (5 treatment groups in 3 RCTs with 260 children) showed that dexmedetomidine use was associated with reduced serum levels of NSE (pooled SMD, -0.54; 95% CI, -0.96 to -0.12) and S-100ß (pooled SMD, -0.85; 95% CI, -1.67 to -0.04) within 24 hours after the surgery. Also, dexmedetomidine use was associated with reduced levels of interleukin-6 (pooled SMD, -1.55; 95% CI, -2.82 to -0.27; 4 treatment groups in 2 RCTs with 190 children). In contrast, the authors observed similar levels of TNF-α (pooled SMD, -0.07; 95% CI, -0.33 to 0.19; 4 treatment groups in 2 RCTs with 190 children) and NF-κB (pooled SMD, -0.27; 95% CI, -0.62 to 0.09; 2 treatment groups in 1 RCT with 90 children) between the dexmedetomidine and control groups. CONCLUSIONS: The authors' findings support the effect of dexmedetomidine on reductions in brain markers among children who undergo cardiac surgery. Further studies would be needed to elucidate its clinically meaningful effects using cognitive functions in the long term, and its effects among children who undergo more complex cardiac surgeries.

Outdoor Play as a Mitigating Factor in the Association Between Screen Time for Young Children and Neurodevelopmental Outcomes.

Importance: Whether the association between higher screen time in infancy and later suboptimal neurodevelopment can be mitigated by frequency of outdoor play is unknown. Objective: To investigate whether higher screen time at age 2 years is associated with neurodevelopmental outcomes at age 4 years and whether this association is mediated by frequency of outdoor play at age 2 years 8 months. Design, Setting, and Participants: Participants were a subsample of the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study, N = 1258). Children were born between December 2007 and March 2012 and followed up from 1 year 6 months to 4 years. The analysis was conducted from April 2021 to June 2022. Exposures: Screen time longer than 1 hour a day at age 2 years was coded as higher screen time. Main Outcomes and Measures: Standardized scores for communication, daily living skills, and socialization domains of the Vineland Adaptive Behavior Scale, second edition, at age 4 years were used (mean [SD], 100 [15]). The mediating factor was frequency of outdoor play at age 2 years 8 months, with 6 or 7 days per week coded as frequent outdoor play. Results: Of 885 participants, 445 children (50%) were female; mean (SD) screen time per day was 2.6 (2.0) hours. Causal mediation analyses revealed that higher screen time at age 2 years was associated with lower scores in communication at age 4 years (nonstandardized coefficient b = -2.32; 95% CI, -4.03 to -0.60), but the association was not mediated by frequency of outdoor play. Higher screen time was also associated with lower scores in daily living skills (b = -1.76; 95% CI, -3.21 to -0.31); 18% of this association was mediated by frequency of outdoor play. Frequency of outdoor play was associated with socialization (b = 2.73; 95% CI, 1.06 to 4.39), whereas higher screen time was not (b = -1.34; 95% CI, -3.05 to 0.36). Conclusions and Relevance: Higher screen time at age 2 years was directly associated with poorer communication at age 4 years. It was also associated with daily living skills, but frequency of outdoor play at age 2 years 8 months alleviated it, suggesting outdoor play mitigated the association between higher screen time and suboptimal neurodevelopment. Future research should specify the nature of the associations and intervention measures, enabling targeted interventions that reduce the potential risk in screen time.

Time trends in emotional well-being and self-esteem in children and adolescents during the COVID-19 pandemic.

OBJECTIVE: Given their unique COVID-19 pandemic experience, it is necessary to evaluate the mental health of youth beyond the initial stages of the pandemic, in relation to the stringency of the social distancing measures. We aimed to describe long-term trends in emotional well-being and self-esteem among youth in Japan during the pandemic. METHOD: Using serial cross-sectional data from April 2020 to December 2021, we evaluated the trends in emotional well-being and self-esteem of youth aged 6-17 years using the self-report KINDL questionnaire, weighted to represent the age and gender distributions in the Japanese population. We then tested the associations between emotional well-being and self-esteem and stringency of social distancing policies, measured using the Oxford COVID-19 Stringency Index. Analyses were also stratified by gender and age group. RESULTS: The emotional well-being and self-esteem of youth improved transiently in 2020, followed by a slight worsening trend into 2021. While emotional well-being stayed lower compared to initial levels nearly 2 years into the pandemic, self-esteem began to improve by late 2021. 12-17 year-olds had lower emotional well-being and self-esteem compared to 6-11 year-olds throughout the study period. Females had lower emotional well-being than males in May 2020 and lower self-esteem than males in May and September/October 2020. More stringent social distancing measures were associated with lower emotional well-being and self-esteem, especially 6-11 year-olds' self-esteem and females' emotional well-being. CONCLUSION: During the COVID-19 pandemic, older youth tended to have lower emotional well-being and self-esteem than younger youth. Younger and female youth were especially vulnerable to stringent social distancing measures.

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction.

During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached ~3 mm in culture. Typical trichogenic signaling pathways were up-regulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, melanosome production and transportation were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, evaluating hair growth and inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment.

Reasons and trends in youth's suicide rates during the COVID-19 pandemic.

Background: The COVID-19 pandemic posed many mental health challenges to youth through unprecedented infection control measures such as nationwide school closures. Despite this, few studies have investigated trends in suicide among youth during the pandemic, let alone their reasons. Methods: Population-level data on crude monthly suicide rates (2016-2021) and reasons of suicide (2018-2020) among youth aged 10-19 years were obtained from the Japanese Ministry of Health, Labour and Welfare and the National Police Agency, respectively. Using an event study design (with a Poisson regression model to calculate changes-in-changes (CiC) estimates) and interrupted time series analysis, we investigated changes in monthly suicide rates during the first 12 months of the pandemic (May 2020 to April 2021) compared to pre-pandemic levels (May 2016 to March 2020). Additionally, we investigated the changes in reasons of suicide (family-related, mental illness, social concerns, and academic concerns). Findings: In the event study analysis, suicide rates among youth increased during the pandemic relative to pre-pandemic levels, especially between August-November 2020 (e.g., ratio of the suicide rate in November 2020 relative to previous years, 1.86; 95% confidence interval (CI), 1.30 to 2.66). Though suicide levels returned closer to pre-pandemic levels by December 2020, they remained slightly elevated into 2021. In the interrupted time series analysis, suicide rates increased from May to August 2020 (0.099 cases per 100,000 youth per month; 95% CI, 0.022 to 0.176), followed by a decrease from September to December 2020 (-0.086 cases per 100,000 youth per month; 95% CI, -0.164 to -0.009). We observed elevated suicide rates for all major reasons from summer to autumn 2020, especially suicides attributed to family-related problems and social concerns. Furthermore, rates of suicides attributed to mental illness remained higher than pre-pandemic levels into December 2020. Interpretation: Suicide rates among youth remained slightly elevated compared to pre-pandemic levels into 2021. The reasons of the increase in suicide rates were multifactorial, including mental health issues and disruptions in social relationships. During a pandemic, interventions that provide mental support as well as opportunities for regular social interactions to youth may be beneficial. Funding: Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education.

Luciferase assay system to monitor fibroblast growth factor signal disruption in human iPSCs.

We describe a protocol for a live-cell luciferase assay system for continuously monitoring fibroblast growth factor (FGF) signal disruption in human-induced pluripotent stem cells (iPSCs). Signal disrupting effects of chemicals are used as an indicator to evaluate toxicity. The assay is reliably predictive of the effects of limb malformation chemicals (AUC = 0.93). The current approach is limited to FGF signal disruption, and combinations with other types of signaling will be required to detect the effects of different toxicants. For complete details on the use and execution of this protocol, please refer to Kanno et al. (2022a).