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Abstract Injury recurrence in young children is a significant public health concern, as it may indicate an unfavorable home environment. This study evaluates whether infantile injuries increase recurrence during preschool years, contributing to more effective prevention strategies for vulnerable families. The study included 20,191 children from “The Longitudinal Survey of Babies in the 21st Century,” a representative sample of infants born in Japan between May 10 and 24, 2010. We conducted a logistic regression analysis to compare injury recurrence risk between children aged 18 months to seven years with and without infantile injury histories. The study revealed that infants with a history of injuries had a higher risk of subsequent hospital visits for injuries during preschool years (crude Odds Ratio (cOR) 1.52, 95% CI, 1.41–1.64, adjusted OR (aOR) 1.48, 95% CI 1.37–1.60). Specific injuries, such as falls (aOR 1.34, 95% CI, 1.26–1.43), pinches (aOR 1.22, 95% CI, 1.15–1.29), drowning (aOR 1.29, 95% CI, 1.19–1.40), ingestion (aOR 1.35, 95% CI, 1.17–1.55), and burns (aOR 1.47, 95% CI, 1.31–1.65), independently increased the risk of future injuries. Our findings highlight the necessity of universal safety measures in the home environment and targeted interventions for families with a history of high-risk injuries.

Abstract Background Previous research has suggested a correlation between postnatal maximum weight loss (MWL) and both neonatal mortality and morbidities in extremely preterm infants. However, the relationship between MWL and neurodevelopmental outcomes remains underexplored. Methods In a single-center, retrospective cohort study at Okayama Medical Center, we evaluated data from extremely preterm infants admitted to the neonatal intensive care unit from 2010 to 2020. Infants who died within the first 10 days of life were excluded. MWL in the first 10 days was the main exposure, categorized into three groups: >15%, 5–15%, and 15% MWL group, 71 in the 5–15% group, and 24 in the 15% MWL; 26.1 weeks and 818 g for 5–15% MWL; and 26.0 weeks and 734 g for 15% (RR 1.32, 95% CI 1.00–1.75) and

Abstract Background The COVID‐19 pandemic has impacted healthcare behaviors, leading to fewer pediatric visits in Japan and potentially fewer visits by adult patients. However, existing Japanese studies on treatment interruptions have generally relied on questionnaire‐based methods. In this study, we assessed the impact of the pandemic on antihypertensive treatment interruption using real‐world prescription data. Methods We conducted an interrupted time series analysis using the National Health Insurance Database in Okayama Prefecture, Japan. Participants included individuals aged 40–69 years with at least one antihypertensive prescription between 2018 and 2020. Treatment interruption was defined as a 3‐month or longer gap in prescriptions after medication depletion. We used segmented Poisson regression with models unadjusted and adjusted for seasonality and over‐dispersion to assess monthly treatment interruptions before and after Japan's April 2020 emergency. Results During the study period, 23.0% of 55,431 participants experienced treatment interruptions. Cyclical fluctuations in interruptions were observed. The crude analysis indicated a 1.2‐fold increase in treatment interruptions following the pandemic; however, the adjusted models showed no significant changes. Even among higher‐risk groups, such as women, younger adults, and those with shorter prescriptions, no significant alterations were observed. Conclusion We found no significant impact of the COVID‐19 pandemic on antihypertensive treatment interruption in Okayama Prefecture. The less severe outbreak in the area or increased use of telemedicine and extended prescriptions may have contributed to treatment continuity. Further research is needed using a more stable and comprehensive database, broader regional data, and detailed prescription records to validate and extend our findings.

Abstract 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.

BackgroundWhile positive pressure ventilation has been considered an important contributing factor associated with pulmonary air leaks, studies examining the association between specific ventilatory settings during acute-phase high-frequency oscillatory ventilation (HFOV) and pulmonary air leaks among extremely preterm infants are limited.MethodsThis was a single-center retrospective cohort study conducted at an institution that primarily used HFOV after intubation in extremely preterm infants. We analyzed data from extremely preterm infants born between 2010 and 2021. The primary outcome was pulmonary air leakage during the first 7 days of life. The exposure variable was the maximum mean airway pressure (MAP) on HFOV during the first 7 days of life or before the onset of pulmonary air leaks. Maximum MAP was categorized into three groups: low (7–10 cmH2O), moderate (11–12 cmH2O), and high (13–15 cmH2O) MAP categories. We conducted robust Poisson regression analyses after adjustment for perinatal confounders, using the low MAP category as the reference.ResultsThe cohort included 171 infants (low MAP, 123; moderate MAP, 27; and high MAP, 21). The median (interquartile range) gestational age and birth weight were 25.7 (24.3–26.7), 25.7 (24.9–26.9), and 25.3 (24.3–26.6) weeks and 760 (612–878), 756 (648–962), and 734 (578–922) g for infants in the low, moderate, and high MAP categories, respectively. Compared to infants in the low MAP category, those in the high MAP category had a higher incidence of pulmonary air leaks (4.1% vs. 33.3%; adjusted risk ratio, 5.4; 95% confidence interval, 1.6–18.5). In contrast, there was no clear difference in the risk of pulmonary air leaks between the moderate and low MAP categories (3.7% vs. 4.1%; adjusted risk ratio, 0.9; 95% confidence interval, 0.1–6.1).ConclusionExtremely preterm infants requiring high MAP (≥13 cmH2O) in acute-phase HFOV had a higher risk of pulmonary air leak during the first 7 days of life.

Abstract The purpose of this study was to assess the associations between delivery room intubation (DRI) and severe intraventricular hemorrhage (IVH), as well as other neonatal outcomes, among extremely preterm infants without low Apgar scores using data from a large-scale neonatal registry data in Japan. We analyzed data for infants born at 24–27 gestational weeks between 2003 and 2019 in Japan using robust Poisson regression. Infants with low Apgar scores (≤ 1 at 1 min or ≤ 3 at 5 min) were excluded. The primary outcome was severe IVH. Secondary outcomes were other neonatal morbidities and mortality. The full cohort included 16,081 infants (intubation cohort, 13,367; no intubation cohort, 2714). The rate of DRI increased over time (78.6%, 2003–2008; 83.4%, 2009–2014; 87.8%, 2015–2019), while the rate of severe IVH decreased (7.1%, 2003–2008; 5.7%, 2009–2014; 5.3%, 2015–2019). Infants with DRI had a higher risk of severe IVH than those without DRI (6.8% vs. 2.3%; adjusted risk ratio, 1.86; 95% confidence interval, 1.33–2.58). The results did not change substantially when stratified by gestational age. Despite conflicting changes over time in DRI and severe IVH, DRI was associated with an increased risk of severe IVH among extremely preterm infants in Japan.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable tool to study SARS-CoV-2 infection. Differentiated IEC monolayers express high levels of angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), host factors essential for SARS-CoV-2 infection. SARS-CoV-2 efficiently grows in IEC monolayers. Using this propagation system, we confirm that TMPRSS2 inhibition blocked SARS-CoV-2 infection in IECs. Hence, our iPSC-derived IEC monolayers are suitable for SARS-CoV-2 research under physiologically relevant conditions.

Abstract 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.

Abstract 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

BackgroundKawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan.MethodsIn total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence.ResultsChildren with higher birth orders were more likely to be hospitalized with KD at 6–18 months of age (second child OR: 1.77, 95% CI: 1.25–2.51; third child OR: 1.70, 95% CI: 1.08–2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57–4.01; third child OR: 2.41, 95% CI: 1.30–4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group.ConclusionsChildren with higher birth orders were at high risk for hospitalization due to KD at 6–18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

Abstract We have shown previously that the lysosomal a3 isoform of the a subunit of vacuolar-type ATPase (V-ATPase) interacts with inactive (GDP-bound form) Rab7, a small GTPase that regulates late endosome/lysosome trafficking, and that a3 recruits Rab7 to secretory lysosomes in mouse osteoclasts. This is essential for outward trafficking of secretory lysosomes and thus for bone resorption. However, the molecular mechanism underlying the recruitment of Rab7 by a3 remains to be fully elucidated. Here, we showed that a3 interacts with the Mon1A-Ccz1 complex, a guanine nucleotide exchange factor (GEF) for Rab7, using HEK293T cells. The interaction was mediated by the amino-terminal half domain of a3 and the longin motifs of Mon1A and Ccz1. Exogenous expression of the GEF promoted the interaction between a3 and Rab7. Mon1A mutants that interact inefficiently with Rab7 interacted with a3 at a similar level to wild-type Mon1A. Lysosomal localization of endogenous Ccz1 was abolished in osteoclasts lacking a3. These results suggest that the lysosomal a3 isoform of V-ATPase interacts with Mon1A-Ccz1, and that a3 is important for Mon1A-Ccz1 localization to secretory lysosomes, which mediates Rab7 recruitment to the organelle.

Abstract Accumulation of senescent cells in various tissues has been reported to have a pathological role in age-associated diseases. Elimination of senescent cells (senolysis) was recently reported to reversibly improve pathological aging phenotypes without increasing rates of cancer. We previously identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as a seno-antigen specifically expressed by senescent human vascular endothelial cells and demonstrated that vaccination against Gpnmb eliminated Gpnmb-positive senescent cells, leading to an improvement of age-associated pathologies in mice. The aim of this study was to elucidate whether GPNMB plays a role in senescent cells. We examined the potential role of GPNMB in senescent cells by testing the effects of GPNMB depletion and overexpression in vitro and in vivo. Depletion of GPNMB from human vascular endothelial cells shortened their replicative lifespan and increased the expression of negative cell cycle regulators. Conversely, GPNMB overexpression protected these cells against stress-induced premature senescence. Depletion of Gpnmb led to impairment of vascular function and enhanced atherogenesis in mice, whereas overexpression attenuated dietary vascular dysfunction and atherogenesis. GPNMB was upregulated by lysosomal stress associated with cellular senescence and was a crucial protective factor in maintaining lysosomal integrity. GPNMB is a seno-antigen that acts as a survival factor in senescent cells, suggesting that targeting seno-antigens such as GPNMB may be a novel strategy for senolytic treatments.

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children.

Sapoviruses, like noroviruses, are single-stranded positive-sense RNA viruses classified in the family Caliciviridae and are recognized as a causative pathogen of diarrhea in infants and the elderly. Like human norovirus, human sapovirus (HuSaV) has long been difficult to replicate in vitro. Recently, it has been reported that HuSaV can be replicated in vitro by using intestinal epithelial cells (IECs) derived from human tissues and cell lines derived from testicular and duodenal cancers. In this study, we report that multiple genotypes of HuSaV can sufficiently infect and replicate in human-induced pluripotent stem cell-derived IECs. We also show that this HuSaV replication system can be used to investigate the conditions for inactivation of HuSaV by heat and alcohol, and the effects of virus neutralization of antisera obtained by immunization with vaccine antigens, under conditions closer to the living environment. The results of this study confirm that HuSaV can also infect and replicate in human normal IECs regardless of their origin and are expected to contribute to future virological studies.

Abstract To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda–mu–sigma) method based on yearly height and weight information (age 1.5–15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

Background: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. Methods: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6–18 months and age 6–66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. Results: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6–66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6–66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. Conclusions: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy. Keywords: Breastfeeding, Cohort, Colostrum, Eczema, Food allergy

Abstract Dietary intake of ω3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid is beneficial for health control. We recently identified 17,18‐epoxyeicosatetraenoic acid (17,18‐EpETE) as a lipid metabolite endogenously generated from eicosapentaenoic acid that exhibits potent anti‐allergic and anti‐inflammatory properties. However, chemically synthesized 17,18‐EpETE is enantiomeric due to its epoxy group—17(S),18(R)‐EpETE and 17(R),18(S)‐EpETE. In this study, we demonstrated stereoselective differences of 17(S),18(R)‐EpETE and 17(R),18(S)‐EpETE in amelioration of skin contact hypersensitivity and found that anti‐inflammatory activity was detected in 17(S),18(R)‐EpETE, but not in 17(R),18(S)‐EpETE. In addition, we found that cytochrome P450 BM‐3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)‐EpETE, which effectively inhibited the development of skin contact hypersensitivity by inhibiting neutrophil migration in a G protein‐coupled receptor 40‐dependent manner. These results suggest the new availability of a bacterial enzyme to produce a beneficial lipid mediator, 17(S),18(R)‐EpETE, in a stereoselective manner. Our findings highlight that bacterial enzymatic conversion of fatty acid is a promising strategy for mass production of bioactive lipid metabolites.

Human norovirus is the leading cause of acute nonbacterial gastroenteritis in people of all ages worldwide. Currently, no licensed norovirus vaccine, pharmaceutical drug, or therapy is available for the control of norovirus infection. Here, we used a rice transgenic system, MucoRice, to produce a variable domain of a llama heavy-chain antibody fragment (VHH) specific for human norovirus (MucoRice-VHH). VHH is a small heat- and acid-stable protein that resembles a monoclonal antibody. Consequently, VHHs have become attractive and useful antibodies (Abs) for oral immunotherapy against intestinal infectious diseases. MucoRice-VHH constructs were generated at high yields in rice seeds by using an overexpression system with RNA interference to suppress the production of the major rice endogenous storage proteins. The average production levels of monomeric VHH (7C6) to GII.4 norovirus and heterodimeric VHH (7C6-1E4) to GII.4 and GII.17 noroviruses in rice seed were 0.54 and 0.28% (w/w), respectively, as phosphate buffered saline (PBS)-soluble VHHs. By using a human norovirus propagation system in human induced pluripotent stem-cell-derived intestinal epithelial cells (IECs), we demonstrated the high neutralizing activity of MucoRice expressing monomeric VHH (7C6) against GII.4 norovirus and of heterodimeric VHH (7C6-1E4) against both GII.4 and GII.17 noroviruses. In addition, MucoRice-VHH (7C6-1E4) retained neutralizing activity even after heat treatment at 90°C for 20 min. These results build a fundamental platform for the continued development of MucoRice-VHH heterodimer as a candidate for oral immunotherapy and for prophylaxis against GII.4 and GII.17 noroviruses in not only healthy adults and children but also immunocompromised patients and the elderly.

Abstract Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking. In osteoclasts lacking a3, lysosomes were not transported to the cell periphery, and Rab7 was not localised to lysosomes but diffused throughout the cytoplasm. Expression of dominant-negative (GDP-bound form) Rab7 inhibited lysosome trafficking in wild-type cells. Furthermore, a3 directly interacted with the GDP-bound forms of Rab7 and Rab27A. These findings reveal a novel role for the proton pump V-ATPase in secretory lysosome trafficking and an unexpected mechanistic link with Rab GTPases.

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

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.

Aircraft impact analysis is needed for safety assessment of nuclear power plants. One of the items which should be analyzed for aircraft impact is physical damage to a reinforced concrete (RC) building and this can be estimated by numerical simulation. In the simulation, a simulation model which has been validated by some experimental data needs to be established. In 1988, an aircraft impact test using an F4 Phantom fighter was conducted at the Sandia National Laboratories in the US and a lot of important experimental data were measured. The numerical simulation results for this aircraft impact test are also introduced in this paper. The relationship between the thickness and the deceleration of the aircraft model is studied and then the differences in the deceleration between the simulation and test results are discussed. The relationship between the failure strain and the destruction modes of the aircraft and the target in the simulation are also studied, and then the differences between the simulation and test results are discussed as well. Through these parametric simulations, the validations of the aircraft and the target model are demonstrated. In evaluating the physical damage area inside the buildings, or discussing the necessary numbers of RC walls until the impacting aircraft stops, it is important to estimate whether the RC walls are perforated by an impacting aircraft. Besides numerical simulations, some empirical equations to estimate them are reported. One of them is the UKAEA equation. This equation estimates a dynamic punching strength of a RC wall. It is determined whether an impacting aircraft perforates a RC wall by comparing the dynamic punching strength with the dynamic impact load of the aircraft. In this paper, several aircraft impact simulations using the established aircraft model with different RC wall thicknesses are conducted. Dynamic punching strength of these RC walls are measured in each simulation. The obtained values in the simulations are compared with the estimated values by the UKAEA equation. The differences between them are investigated and the reasons of these differences are discussed.

There is an increasing demand for genetically modified mice produced without crossing, for rapid phenotypic screening studies at the organismal level. For this purpose, generation of completely embryonic-stem-cell (ESC)-derived chimeric mice without crossing is now possible using a microinjection or aggregation method with 3i culture medium. However, the microinjection of ESCs into blastocyst, morula, or 8-cell-stage embryos requires a highly skilled operator. The aggregation method is an easier alternative, but the conventional aggregation protocol still requires special skills. To make the aggregation method easier and more precise, here we developed a micro-aggregation device. Unlike conventional 3-dimensional culture, which uses hanging-drop devices for aggregation, we fabricated a polystyrene funnel-like structure to smoothly drop ESCs into a small area (300-μm in diameter) at the bottom of the device. The bottom area was designed so that the surface tension of the liquid-air interface prevents the cells from falling. After aggregation, the cells can be recovered by simply exerting pressure on the liquid from the top. The microdevice can be set upon a regular 96-well plate, so it is compatible with multichannel pipette use or machine operation. Using the microdevice, we successfully obtained chimeric blastocysts, which when transplanted resulted in completely ESC-derived chimeric mice with high efficiency. By changing the number of ESCs in the aggregate, we found that the optimum number of co-cultured ESCs was around 90~120 per embryo. Under this condition, the efficiency of generating completely ESC-derived mice was the same or better than that of the injection method. These results indicated that our microdevice can be used to produce completely ESC-derived chimeric mice easily and with a high success rate, and thus represents a promising alternative to the conventional microinjection or aggregation method, especially for high-throughput, parallel experimental applications.

Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

The authors earlier developed a model to predict the heat flux distribution in an arc driven by an AC magnetic field. That theoretical model implied that the heat flux distribution depended on waveforms of the imposed AC magnetic field. Experiments were conducted in this study to validate that theoretical prediction. Theoretical calculations of heat flux distribution in the arc driven by AC magnetic field were conducted using the heat flux profile in the arc root obtained from the measurement under no magnetic field. The heat flux distributions in arcs driven by AC magnetic fields were measured by imposing two AC magnetic fields with sinusoidal and rectangular waveforms. Agreement between experimental and theoretical heat flux distributions was good. Results confirm that heat flux profiles of various types are producible by controlling the imposed magnetic flux density and its waveform.

Theoretical consideration of a magnetically driven arc was performed to elucidate the variation of heat flux with an imposed DC magnetic field. Experiments were conducted to confirm the validity of the theoretical model. The heat flux decreased concomitantly with increased imposed magnetic flux density. Theoretical predictions agreed with experimental results.