Dual-color live imaging unveils stepwise organization of multiple basal body arrays by cytoskeletons.

For mucociliary clearance of pathogens, tracheal multiciliated epithelial cells (MCCs) organize coordinated beating of cilia, which originate from basal bodies (BBs) with basal feet (BFs) on one side. To clarify the self-organizing mechanism of coordinated intracellular BB-arrays composed of a well-ordered BB-alignment and unidirectional BB-orientation, determined by the direction of BB to BF, we generated double transgenic mice with GFP-centrin2-labeled BBs and mRuby3-Cep128-labeled BFs for long-term, high-resolution, dual-color live-cell imaging in primary-cultured tracheal MCCs. At early timepoints of MCC differentiation, BB-orientation and BB-local alignment antecedently coordinated in an apical microtubule-dependent manner. Later during MCC differentiation, fluctuations in BB-orientation were restricted, and locally aligned BB-arrays were further coordinated to align across the entire cell (BB-global alignment), mainly in an apical intermediate-sized filament-lattice-dependent manner. Thus, the high coordination of the BB-array was established for efficient mucociliary clearance as the primary defense against pathogen infection, identifying apical cytoskeletons as potential therapeutic targets.

Tracking handgrip strength in Kendo athletes from university to middle and older adulthood.

OBJECTIVE: This study aimed to compare the current handgrip strength (HGS) of Kendo athletes with their HGS when they were in university (up to 50 years). METHODS: Eighty male graduates who were Kendo club members during their university days performed anthropometric and HGS measurements, and these HGS were compared with those measured during their university days (mean age of 19.5 years old). RESULTS: There was no evidence of a statistical difference in HGS between the current measurement and the measurement taken during university [-0.64 (-1.9, 0.67) kg, p = .336]. There was, however, evidence that the difference in HGS depended upon the current age of the individual (t = -6.43, p < .001). When probing the interaction, there were statistical differences between the ages of 24.6 and 38.2 years and between the ages of 47.4 and 69.9 years. Strength increased across time in the younger participants and decreased for those who were older. Between the ages of 38.9 and 46.1 years, there was no evidence of a statistical difference indicating a maintenance of strength. CONCLUSION: The HGS of Kendo club graduates, which they acquired during their formative years, continued to increase even after they graduated from university and entered their 30s. However, their HGS decreased from age 50, even though they practiced Kendo.

Athletes in sporting events with upper-body gripping movements have greater handgrip strength than those in sporting events that prioritize the lower body.

OBJECTIVE: Evidence suggests that acquiring a high level of handgrip strength early in life and maintaining that strength throughout life may be important for health. In addition, it is thought that sports activities performed during the developmental period are effective in improving handgrip strength, but it is unknown what types of sports are more effective. As a first step, we conducted a cross-sectional study to compare handgrip strength across different sports (upper-body gripping sports vs. lower body) in early adulthood. METHODS: We used the Juntendo Fitness Plus Study data from 1973 to 2018 and selected two types of sporting events with matching physiques (soccer, baseball, and kendo) but different degrees of gripping. Data on 7344 male first-year sports university students included 1127 soccer, 297 Kendo, and 698 baseball players. RESULTS: Those in the lower body-only (soccer) sports had -3.78 (95% CI: -4.27, -3.29) kg lower handgrip strength than those in the lower + upper (kendo and baseball). Comparing each individual sport found that each sport was different from each other with Kendo > Baseball > Soccer (between each sport, p < .001). In addition, the difference between sports has become greater across time. CONCLUSIONS: In early adulthood, handgrip strength is greatest in those participating in sports with upper-body movements compared to those participating in sports that mainly involved lower-body movements. The three sports we selected are natural activities that do not directly train handgrip strength. Therefore, sport may be one potential method to improve low handgrip strength in children/adolescents during the developmental period.

The associations between meeting 24-hour movement guidelines and adiposity in Asian Adolescents: The Asia-Fit Study.

Less is known about how compliance with 24-hour movement guidelines for physical activity (PA), sedentary behavior, and sleep affects adiposity in young people. The purposes of this study were to compare compliance with 24-hour movement guidelines in Asian adolescents and to examine the associations between compliance with 24-hour movement guidelines and body fat percentage. A sample of 12 590 adolescents aged 13.63 (± 1.01) years from eight Asian metropolitan cities including Bangkok (Thailand), Hong Kong SAR, Kuala Lumpur (Malaysia), Seoul (South Korea), Shanghai (China), Singapore, Taipei (Taiwan), and Tokyo (Japan) completed interviewer-administered questionnaires to assess moderate-to-vigorous PA, recreational screen time, sleep duration, and covariates. Body fat percentage was measured using bioelectrical impedance analysis. We found that compliance with 24-hour movement guidelines differed in Asian adolescents across the eight cities. Adjusting for covariates, there was a negative association between number of the guidelines being met and body fat percentage in Asian adolescents. In addition, meeting only the sleep guideline and both the PA and sleep guidelines had negative associations with body fat percentage compared with no guidelines being met. Our findings improve the understanding about how compliance with 24-hour movement guidelines benefit a healthy body weight in adolescents, as well as contribute to development of evidence-based 24-hour movement guidelines for Asian young people. Future research is needed to gain better insights into the directionality of the associations between compliance with 24-hour movement guidelines and adiposity, as well as the mechanisms underlying the associations in Asian adolescents.

Validation of Self-Monitoring Devices Supporting Sodium Intake Reduction: An Experimental Feeding Study Using Standardized Low-Salt and High-Salt Meals among Healthy Japanese Volunteers.

INTRODUCTION: Although several approaches for approximating daily Na intake and the Na/K ratio using casual urine are available, the most useful method remains unclear during daily practice and at home. METHODS: Twenty-seven participants measured their casual urinary Na/K ratio repeatedly using a Na/K ratio monitor and also measured overnight urine once daily using a monitoring device which delivers on-site feedback to estimate their salt intake under unrestricted, low-salt (LS) (6 g/day), and high-salt (HS) (12 g/day) diets. RESULTS: The monitoring method utilizing overnight urine to estimate daily Na remained insensitive, resulting in significant overestimation during the LS diet and underestimation during the HS diet periods; estimated salt intake during the LS and HS diet periods plateaued at 7-8 g/day and 9-10 g/day within 3 day; mean estimated salt intake was 11.3 g/day, 7.9 g/day, and 9.8 g/day on the last day of the unrestricted, LS, and HS diets; the coefficient of variation (CV) of the estimated Na intake was 0.23 and 0.17 in the latter half of the low- and high-salt diet periods, respectively. The mean urinary Na/K molar ratio was 5.6, 2.5, and 5.3 on the last day of the unrestricted, LS, and HS diets; the CV of the daily mean Na/K ratio was 0.41 and 0.36 in the latter half of the LS and HS diet periods, respectively. The urinary Na/K ratio during the LS and HS diet periods plateaued within 2 days. The monitoring method based on the daily mean of the casual urinary Na/K ratio reflected the actual change in Na intake, and the estimated value tracked the actual changes in salt intake with smaller difference than the overnight urine estimates when using the estimation coefficient set at 2; estimated salt intake during the LS and HS diet periods plateaued at 5-6 g/day and 10-12 g/day within 2-3 day; mean estimated salt intake was 11.0 g/day, 5.7 g/day, and 10.7 g/day on the last day of the unrestricted, LS, and HS diets, respectively. DISCUSSION/CONCLUSION: Estimates of daily Na intake derived from overnight urine may remain insensitive during dietary interventions. The urinary Na/K ratio reflects the actual change in Na intake during dietary modification and may serve as a practical marker, particularly during short-term interventions. Conversion from the urinary Na/K ratio to estimated salt intake may be useful, if the coefficient was set appropriate by further investigations.

Association of physical fitness and motor ability at young age with locomotive syndrome risk in middle-aged and older men: J-Fit+ Study.

BACKGROUND: Physical fitness and motor ability are associated with the incidence of locomotive syndrome (LS) in older adults. The relationships between physical fitness and motor ability at a young age to LS risk in later life remain unclear. This study examined the association between physical fitness and motor ability among university students and their risk of LS in middle and old age. METHODS: The participants were 231 male alumni aged 48-65 years from the Department of Physical Education of a university in Japan. Physical fitness and motor ability test results during their fourth year at the university were used. Physical fitness tests included the side-step test, vertical jump test, back muscle, grip strength, trunk lift, standing trunk flexion, and step-test. Motor ability was tested using the 50-m and 1500-m run, running long jump, hand-ball throw, and pull-up test. LS risk was assessed using a seven-question standardized self-administered Loco-check questionnaire. Participants were divided into three groups (low, medium, and high) based on physical fitness and motor ability test results at young age, and LS risk was assessed at an older age across the three groups using Cox proportional hazards models. RESULTS: From the 2017 follow-up survey, the median follow-up period was 37 years (interquartile range, 33-41), and LS risk was suspected for 31 (13.4%) participants. Better performance on the side-step test was associated with the reduced risk of LS (hazard ratio 0.32; 95% confidence interval, 0.101-0.983, P = 0.047). CONCLUSIONS: Good agility (side-step test) at a young age may reduce the future risk of LS among middle-aged and older men.

Engagement in different sport disciplines during university years and risk of locomotive syndrome in older age: J-Fit+ Study.

BACKGROUND: Among former Olympic-level athletes, engagement in different sport disciplines has been associated with mortality risk in subsequent years. However, limited evidence is available on whether engagement in different sport disciplines at a young age is associated with locomotive syndrome (LS) risk later in life. This study examined the relationship between engagement in different sport disciplines during university years and LS risk in older age among former university athletes. METHODS: Participants were 274 middle-aged and 294 older men alumni who graduated from a school of physical education in Japan. LS risk was defined as answering "yes" to any of the Loco-check questions. Data on university sports club membership were collected using questionnaires. University clubs were classified into three groups of cardiovascular intensity (low, moderate, high), following the classification system of sport disciplines by the American College of Cardiology. This classification considers the static and dynamic components of an activity, which correspond to the estimated percent of maximal voluntary contraction reached and maximal oxygen uptake achieved, respectively. University clubs were grouped based on the risk of bodily collision (no, yes) and extent of physical contact (low, moderate, high). Relationships between engagement in different sport disciplines and LS risk were analyzed using Cox proportional hazards models, and adjusted for age, height, weight, joint disease, habitual exercise, and smoking and drinking status. RESULTS: Adjusted hazard ratios and 95% confidence intervals associated with the low, moderate, and high cardiovascular intensity sports were 1.00 (reference), 0.48 (0.22-1.06, P = 0.070), and 0.44 (0.20-0.97, P = 0.042) in older men, respectively; however, there was no significant association between these parameters among middle-aged men. Engagement in sports associated with physical contact and collision did not affect LS risk in either group. CONCLUSIONS: Engagement in sports associated with high cardiovascular intensity during university years may reduce the risk of LS in later life. Encouraging young people to participate in such activities might help reduce LS prevalence among older populations.

Cep128 associates with Odf2 to form the subdistal appendage of the centriole.

The mother centriole in a cell has two appendages, the distal appendage (DA) and subdistal appendage (SDA), which have roles in generating cilia and organizing the cellular microtubular network, respectively. In the knockout (KO) cells of Odf2, the component of the DA and SDA, both appendages simultaneously disappear. However, the molecular mechanisms by which the DA and SDA form independently but close to each other downstream of Odf2 are unknown. Here, using super-resolution structured illumination microscopy (SR-SIM), we found that the signal for GFP-tagged Odf2 overlapped considerably with that of immunofluorescently labeled Cep128. We further found that Cep128 knockdown (KD) caused the dissociation of other SDA components from the centriole, including centriolin, Ndel1, ninein and Cep170, whereas Odf2 was still associated with the centriole. In contrast, the DA components remained associated with the centriole in Cep128 KD cells. Consistent with this observation, we identified Cep128 as an Odf2-interacting protein by immunoprecipitation. Taken with the finding that Cep128 deletion decreased the stability of centriolar microtubules, our results indicate that Cep128 associates with Odf2 in the hierarchical assembly of SDA components to elicit the microtubule-organizing function.

Accelerated skeletal maturation is associated with overweight and obesity as early as preschool age: a cross-sectional study.

BACKGROUND: Body mass index (BMI) and skeletal age (SA) are important indicators of individual growth and maturation. Although the results have not been unified, most studies indicated that accelerated skeletal maturation is associated with overweight/obesity. However, there have so far been insufficient studies about the association between accelerated skeletal maturation and overweight/obesity in preschoolers, particularly Asian children. A cross-sectional study was conducted on Chinese children to verify the association between accelerated skeletal maturation and overweight/obesity at preschool age. METHODS: The study involved 1330 participants aged 3.1-6.6 years old (730 males and 600 females) in Shanghai, China. The skeletal age was determined according to the method of TW3-C RUS. Accelerated skeletal maturation was defined as relative SA (SA minus chronological age [CA]) ≥1.0 years. BMI was classified as thinness, normal weight, overweight, and obesity according to the International Obesity Task Force (IOTF) BMI cut-offs. The Chi-square was performed to determine the statistically significant difference in the frequency of accelerated skeletal maturation in BMI and age categories. The logistic regression model analyzed the association between accelerated skeletal maturation and overweight/obesity. RESULTS: The percentage of accelerated skeletal maturation increased with BMI (7.8% of children in thinness group had accelerated skeletal maturation; the percentage increased to 30.8% in obese group. x2 = 89.442, df = 3, P < 0.01) and age group (at age 3.5, 3.5% of participants had accelerated skeletal maturation; at age 6.0 years, this increased to 27.8%. x2 = 43.417, df = 5, P < 0.01). Logistic regression analysis showed that children with overweight and obesity are more likely to have accelerated skeletal maturation than children with normal weight after adjusting for gender and age (Overweight, odds ratio [OR] = 3.27, 95% confidence interval [CI]: 2.20-4.87; Obese, OR = 4.73, 95% CI: 2.99-7.48). CONCLUSIONS: There is an association between accelerated skeletal maturation and overweight/obesity among preschool children. This study suggests that accelerated skeletal maturation might coexist with overweight/obesity in preschool children, and interventions, such as dietary modifications and increasing levels of physical activity, should be employed to prevent both accelerated skeletal maturation and overweight/obesity as early as preschool age.

Physical activity and health-related fitness in Asian adolescents: The Asia-fit study.

Purpose: The present study aimed to investigate and compare physical activity (PA) and health-related fitness in Asian adolescents, and to examine the associations between meeting PA guidelines and attaining fitness standards. Methods: A sample of 12,590 adolescents (Mage = 13.63 years, SD = 1.01) from eight Asian metropolitan cities completed measurements of PA, five field-based fitness tests, and covariates. The fitness test scores were further classified into Healthy Fitness Zone (HFZ) or Needs Improvement Zone (NIZ). Results: Findings showed that adolescents' levels of PA and fitness components differed by cities. City differences were also found in proportions of meeting PA guidelines and achieving the HFZs of aerobic capacity, muscular fitness, and body composition. After controlling covariates, meeting PA guidelines positively associated with being in the HFZs of aerobic and muscular fitness, but the association was not significant with being in the body composition HFZ. Conclusion: There was a large variation in PA and health-related fitness in adolescents across the eight Asian cities. Asian adolescents achieving PA guidelines were more likely to be in the HFZ of aerobic and muscular fitness. Prospective follow-up studies are warranted to gain better insights into the relationships between objectively-measured PA and fitness.

Secular trends in the grip strength and body mass index of sport university students between 1973 and 2016: J-Fit＋study.

Sport university students are a unique population because they usually have a strong sport background since early childhood. In this study, we aimed to examine secular trends in grip strength of male, first-year sport university students in comparison with the general population between 1973 and 2016. Existing data on the grip strength of 6,308 sport university students aged 18 years were examined. The data were obtained from the Juntendo Fitness Plus Study, a study of the Department of Physical Education/Health and Sports Science of Juntendo University. For reference, age- and sex-matched data (18 years old, male) on the grip strength were obtained from a national database. Compared with the general population, the sport university students had greater body mass index and stronger grip strength at all times. The grip strength of sport university students significantly declined between the 1980s and 1990s, and it has plateaued since 2000, albeit at low levels. Compared with the peak performance of sport university students in 1984, the grip strength of students in 2016 was significantly lower by 8.1 kg. The downward trends were also confirmed in the general population during the same periods. In conclusion, the grip strength of sport university students has significantly declined over the last few decades.

Moderate-to-vigorous physical activity attenuates the detrimental effects of television viewing on the cardiorespiratory fitness in Asian adolescents: the Asia-fit study.

BACKGROUND: Moderate-to-vigorous physical activity (MVPA) and television viewing are independently associated with cardiorespiratory fitness. However, limited evidence is available on their combined effects, specifically of MVPA and watching television, on cardiorespiratory fitness in the young Asian population. Therefore, the present study examined whether MVPA can attenuate the detrimental effects of prolonged television viewing on the cardiorespiratory fitness of Asian adolescents. METHODS: This is a cross-sectional study on 9553 adolescents (aged 12-15 years) from 8 Asian metropolitan cities (Tokyo, Hong Kong, Shanghai, Taipei, Bangkok, Kuala Lumpur, Seoul, and Singapore). Cardiorespiratory fitness was assessed by using a 15-m progressive aerobic capacity endurance run (PACER) test. The time spent on MVPA and watching television was assessed using the International Physical Activity Questionnaire-Short Form. RESULTS: MVPA was more closely associated with the PACER score than the duration of watching television. Compared with the reference group (i.e. those with the lowest levels of MVPA [< 30 min/day] and the most sedentary [≥3 h/day of television time]), PACER scores were significantly higher for those who met the physical activity recommendation (≥60 min/day in MVPA), regardless of the duration of television viewing. Conversely, girls in the least active group (< 30 min/day of MVPA) who watched television < 1 h/day demonstrated better PACER scores than the reference group. CONCLUSIONS: Sufficient MVPA (≥60 min/day) can attenuate the detrimental effects of excessive television viewing with cardiorespiratory fitness in Asian adolescents. In addition, the duration of television viewing had significant but weaker associations with cardiorespiratory fitness compared to MVPA.

Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. It was recently noted that the characteristics of epidermal barrier functions critically influence the pathological features of AD. Evidence suggests that claudin-1 (CLDN1), a major component of tight junctions (TJs) in the epidermis, plays a key role in human AD, but the mechanism underlying this role is poorly understood. One of the main challenges in studying CLDN1's effects is that Cldn1 knock-out mice cannot survive beyond 1 d after birth, due to lethal dehydration. Here, we established a series of mouse lines that express Cldn1 at various levels and used these mice to study Cldn1's effects in vivo. Notably, we discovered a dose-dependent effect of Cldn1's expression in orchestrating features of AD. In our experimental model, epithelial barrier functions and morphological changes in the skin varied exponentially with the decrease in Cldn1 expression level. At low Cldn1 expression levels, mice exhibited morphological features of AD and an innate immune response that included neutrophil and macrophage recruitment to the skin. These phenotypes were especially apparent in the infant stages and lessened as the mice became adults, depending on the expression level of Cldn1 Still, these adult mice with improved phenotypes showed an enhanced hapten-induced contact hypersensitivity response compared with WT mice. Furthermore, we revealed a relationship between macrophage recruitment and CLDN1 levels in human AD patients. Our findings collectively suggest that CLDN1 regulates the pathogenesis, severity, and natural course of human AD.

Results from the Japan's 2018 report card on physical activity for children and youth.

BACKGROUND: The momentum to promote physical activity (PA) by various government agencies such as the Japan Sports Agency established in 2015, academic organizations, and companies is increasing towards the Tokyo Olympic and Paralympic Games. The goal of the 2018 Japan Report Card on Physical Activity for Children and Youth is to assess and track levels of health behaviors related to PA in Japanese children and youth, facilitators and barriers for PA, and related health outcomes. METHODS: Nationally representative data were used to score the indicators. RESULTS: The 2018 Japan Report Card on Physical Activity for Children and Youth consists of health behaviors and outcomes (7 indicators), and influences on health behaviors (4 indicators). The key four health behaviors and outcomes (Organized Sport Participation: B-; Active Transportation: A-; Physical fitness: A, Weight status: A) were favorable. Sedentary Behavior received C- grade, while 2 indicators (Overall Physical Activity, and Active Play) could not be graded. In the Influences domain, Family Influence and Community were graded as C-, while School (B+), Community and Environment (B-), and Government Strategies and Investments (B) were favorable. CONCLUSIONS: The 2018 Japan Report Card on Physical Activity for Children and Youth shows that Japanese children and youth have favorable levels of organized sport participation, active transportation to and from school, and physical fitness and weight status. Future nationally representative surveys on overall PA and active play are needed.

A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. METHODS: The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. RESULTS: Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. CONCLUSIONS: The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.

Chronotype and emotional/behavioral problems mediate the association between leisure screen time and academic achievement in children.

Leisure screen time is associated with poor academic achievement; however, the mechanism underlying this relationship is unclear. Chronotypes and emotional/behavioral problems may be linked to this association. This study aimed to examine the associations between leisure screen time, chronotype, emotional/behavioral problems, and academic achievement using mediation analysis. A total of 113 children aged 9-12 years participated in this study. All participants were assessed for leisure screen time, chronotype, emotional/behavioral problems, and academic achievement. Leisure screen time was evaluated using a self-reported questionnaire. Chronotypes were measured using The Japanese Children's Chronotype Questionnaire, and the morningness/eveningness (M/E) score was calculated. Emotional/behavioral problems were assessed using The Japanese Strengths and Difficulties Questionnaire, and the total difficulties score (TDS) was calculated. Academic achievement was assessed by the homeroom teacher for each of the seven school subjects. Partial correlation analysis adjusted for grade, sex, and sleep duration indicated that leisure screen time was associated with M/E scores and academic achievement (p < 0.05). There was a positive association between M/E score and TDS (p < 0.05) and a negative association between TDS and academic achievement (p < 0.05). A mediation analysis adjusted for grade, sex, and sleep duration was performed. There was a significant total effect of leisure screen time on academic achievement (p < 0.05). Additionally, the M/E score and TDS significantly mediated the association between leisure screen time and academic achievement (p < 0.05). Our findings suggest that the serial path between chronotype and emotional/behavioral problems weakly but significantly mediates the association of leisure screen time with academic achievement.

Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of interleukin-1ß, and atrophic gastritis in mice.

BACKGROUND & AIMS: Although defects in tight junction (TJ) epithelial paracellular barrier function are believed to be a primary cause of inflammation, the mechanisms responsible remain largely unknown. METHODS: We generated knockout mice of stomach-type claudin-18, a major component of TJs in the stomach. RESULTS: Cldn18(-/-) mice were afflicted with atrophic gastritis that started on postnatal day 3. This coincided with a decrease in intragastric pH due to H(+) secretion from parietal cells and concomitant up-regulation of the cytokines, interleukin-1ß, cyclooxygenase-2, and KC, resulting in spasmolytic polypeptide-expressing metaplasia (SPEM). Oral administration of hydrochloric acid on postnatal day 1 induced the expression of these cytokines in Cldn18(-/-) infant stomach, but not in Cldn18(+/+) mice. A paracellular H(+) leak in Cldn18(-/-) stomach was detected by electrophysiology and H(+) titration, and freeze-fracture electron microscopy showed structural defects in the TJs, in which the tightly packed claudin-18 (stomach-type)-based TJ strands were lost, leaving a loose meshwork of strands consisting of other claudin species. CONCLUSIONS: These findings provide evidence that claudin-18 normally forms a paracellular barrier against H(+) in the stomach and that its deficiency causes paracellular H(+) leak, a persistent up-regulation of proinflammatory cytokines, chronic recruitment of neutrophils, and the subsequent development of SPEM in atrophic gastritis.

Proposal of anti-moesin as a novel biomarker for ANCA-associated vasculitis.

Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) in microscopic polyangiitis (MPA). MPO-ANCA activates neutrophils by binding to cell surface MPO expressed on tumor necrosis factor-α (TNF-α)-primed neutrophils and induces neutrophil degranulation and production of reactive oxygen species, consequently resulting in glomerular endothelial damage. Recently, anti-MPO antibody has been found to activate glomerular endothelial cells, leading to an upregulation of adhesion molecules. MPO-ANCA, however, is not always correlated with disease activity in MPA. Accordingly, the molecule(s) responsible for the anti-MPO antibody have been explored on mouse glomerular endothelial cells. The molecule was identified as moesin, which is a heparin-binding protein and belongs to the ezrin/radixin/moesin family of proteins distributed in the plasma membrane in the cellular cortex. Interestingly, anti-moesin is observed in sera of SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN, and of patients with MPO-AAV. The activation of glomerular endothelial cells by the anti-MPO antibody appears to be associated with signaling through moesin.

Physical fitness before and during the COVID-19 pandemic: Results of annual national physical fitness surveillance among 16,647,699 Japanese children and adolescents between 2013 and 2021.

BACKGROUND: Limited nationally representative evidence is available on temporal trends in physical fitness (PF) for children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic. The primary aim was to examine the temporal trends in PF for Japanese children and adolescents before and during the COVID-19 pandemic. The secondary aim was to estimate the concurrent trends in body size (measured as body mass and height) and movement behaviors (exercise, screen, and sleep time). METHODS: Census PF data for children in Grade 5 (aged 10-11 years) and adolescents in Grade 8 (aged 13-14 years) were obtained for the years 2013-2021 from the National Survey of Physical Fitness, Athletic Performance, and Exercise Habits in Japan (n = 16,647,699). PF and body size were objectively measured, and movement behaviors were self-reported. Using sample-weighted linear regression, temporal trends in mean PF were calculated before the pandemic (2013-2019) and during the pandemic (2019-2021) with adjustments for age, sex, body size, and exercise time. RESULTS: When adjusted for age, sex, body size, and exercise time, there were significant declines in PF during the pandemic, with the largest declines observed in 20-m shuttle run (standardized (Cohen's) effect size (ES) = -0.109 per annum (p.a.)) and sit-ups performance (ES = -0.133 p.a.). The magnitude of the declines in 20-m shuttle run and sit-ups performances were 18- and 15-fold larger, respectively, than the improvements seen before the pandemic (2013-2019), after adjusting for age, sex, body size, and exercise time. During the pandemic, both body mass and screen time significantly increased, and exercise time decreased. CONCLUSION: Declines in 20-m shuttle run and sit-ups performances suggest corresponding declines in population health during the COVID-19 pandemic.

Associations of Morphological Changes in Skeletal Muscles of Preschool Children in China Following Physical Activity.

PURPOSE: Physical activity (PA) is likely to be the most important modifiable factor in skeletal muscle development. However, the influence of PA on the skeletal muscle of preschool children has not been thoroughly investigated. The main objective of this study was to quantitatively measure PA, and then, to assess whether associations exist between site-specific muscle changes and PA in relation to sex and weight statuses in preschool children aged 3 to 4 years. METHODS: A total of 86 healthy preschool children, aged 3-4 years, were instructed to wear an accelerometer for seven consecutive days. The number of steps taken daily, and minutes spent in moderate-vigorous PA (MVPA) and total PA (TPA) were recorded. Muscle thickness was measured by B-mode ultrasonography using a 5-18 MHz scanning head. Muscle thickness was measured at seven sites: the lateral forearm, upper arm, abdomen, anterior and posterior thigh, and anterior and posterior lower leg. RESULTS: There was no significant difference between boys and girls in terms of MVPA and TPA on weekdays and weekends. According to the linear regression models, after adjusting for daylight duration, the muscle of the posterior thigh was significantly positively associated (p < 0.05) with daily steps and MVPA on weekdays for boys and girls, respectively. CONCLUSIONS: We found that the muscle thickness of the posterior thigh in preschool children was significantly positively associated with PA, as measured by daily steps and MVPA. We suggest that for the overall health and well-being of preschool children, the levels of PA should be maintained and/or increased, and preferably transformed into a regular part of daily living.