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.

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.

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.

Qualitative study of the association between psychosocial health and physical activity/sleep quality in toddlers.

Physical activity and sleep are important factors of mental and physical health in children, with some reports indicating that their effects can persist into adulthood. However, there is limited research on the qualitative aspects of physical activity and sleep in preschool children, particularly in those aged < 3 years. Therefore, to elucidate the association between psychosocial health and physical activity/sleep in early childhood in terms of qualitative aspects, we conducted a retrospective cohort study in 2985 3-year-old children (37.2 ± 0.75 months) in Shanghai, China. An analysis using structural equation modeling indicated that current physical activity had a direct and moderate impact on current psychosocial health evaluated using the Strength and Difficulties Questionnaire. In particular, past physical activity had an indirect and mild effect on current psychosocial health via current physical activity in girls. However, regardless of sex, past sleep quality had slight impact on current psychosocial health, not only indirectly via current sleep quality, but also directly. These findings highlight the importance of considering the qualitative aspects of physical activity and sleep quality as significant factors influencing the current and future psychosocial health of children, even at a very early age (< 3 years).

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.

Double mutation of claudin-1 and claudin-3 causes alopecia in infant mice.

Hair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)-1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3-knockout (Cldn1Δ/Δ Cldn3-/- ) mice. Although hair growth was normal, Cldn1Δ/Δ Cldn3-/- mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/Δ Cldn3-/- mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.

Relationship between Skeletal Muscle Thickness and Physical Activity in 4- to 6-Year-Olds in Japan.

PURPOSE: Physical activity (PA) is widely recognized as a key factor in promoting skeletal muscle growth, though little is known about the specific impact of PA on the skeletal muscle development of preschool children. The purpose of this study is to investigate whether there is a relationship between PA levels and skeletal muscle thickness in preschoolers. By exploring this relationship, we hope to gain a better understanding of how PA can be used to promote healthy skeletal muscle development in preschoolers. METHODS: In this study, a total of 275 healthy Japanese preschoolers, aged 4-6 years, from seven nursery schools in the town of Togo were recruited. Participants were asked to wear an accelerometer for four consecutive days to record their daily steps and the amount of time spent in moderate-to-vigorous PA and t total physical activity. Muscle thickness (MTs) was measured using B-mode ultrasonography at four sites: the anterior and posterior thigh (AT and PT, respectively) and the anterior and posterior lower leg (AL and PL, respectively). RESULTS: On weekdays, boys were found to be more physically active and engaged in significantly higher levels of total physical activity and moderate-to-vigorous PA than girls. Both boys and girls recorded more physical activity, daily steps, and higher levels of total physical activity and MVPA on weekdays compared to weekends. After adjusting for daylight duration, multivariable regression analyses revealed that increased total physical activity and moderate-to-vigorous PA were positively associated with greater muscle thickness size in the anterior tibialis (AT) and posterior lower leg (PL) muscles (ß = 1.11 and ß = 1.37 for AT, ß = 1.18 and ß = 0.94 for PL, p < 0.05) in Japanese preschoolers. CONCLUSIONS: The time spent involved in most of the different categories of moderate-to-vigorous PA was significantly higher for boys than for girls on the weekdays and weekends. Additionally, there was a positive correlation between time spent in moderate-to-vigorous PA and greater development of skeletal muscle in the lower body.

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.

Prevalence of dry eye syndrome and risk factors in physical education and sports science graduates.

PURPOSE: There are only a few epidemiological studies of dry eye syndrome (DES) in populations with a common academic background. in this study, the prevalence of DES and associated factors were evaluated separately in men and women physical education and sports science graduates. STUDY DESIGN: Cross-sectional survey. METHODS: A questionnaire about the diagnosis of DES and associated factors was mailed to 9507 graduates of the Faculty of Health and Sports Science, Juntendo University. The questions covered subjective DES using Schaumberg et al.'s questionnaire and the prevalence of diagnosed DES. Associated factors, age, sex, smoking, alcohol consumption, body mass index, daily screen viewing time, and contact lens (CL) use were analyzed. RESULTS: A total of 2048 valid responses were received. The prevalence of diagnosed DES was 2.9% in men and 9.3% in women. For subjective DES, the prevalence was 14.8% in men and 39.8% in women. The odds ratio for DES was high in men and women who used CLs and women whose daily screen viewing time was ≥ 4 h. CONCLUSION: Both diagnosed and subjective DES were highly prevalent in men and women of all ages, particularly among those in their 20 and 30s. CL use was associated with DES in both men and women. Measures to deal with the factors that can be corrected might have a positive effect on the ocular health and quality of life of physical education and sports science graduates.

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.

Handgrip Strength and Healthspan: Impact of Sports During the Developmental Period on Handgrip Strength (Juntendo Fitness Plus Study).

Handgrip strength as a biomarker is being studied as a factor in predicting disease onset. However, the effect of improving handgrip strength through physical exercises, such as sports during the developmental period, on disease prevention has yet to be fully elucidated. The Juntendo Fitness Plus (J-Fit Plus) Study is a unique database of anthropometric and physical fitness measurements with over 50 years of accumulated data. It has the potential to explore the effects of sports on the association between handgrip strength and morbidity/mortality. We first outline previous studies on the impact of physical exercise interventions on handgrip strength, separated into adulthood and developmental period. We then introduced a unique effort to investigate the effects of sports using the J-Fit Plus Study database and describe the challenges of finally elucidating the impact of exercise on the association between handgrip strength and health status.

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma.

Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM.

Field-based physical fitness assessment in preschool children: A scoping review.

Physical fitness, which can be measured using various health- and skill-related components, is an important indicator of child development and health status. This study undertakes a scoping review on physical fitness assessment methods in preschool children to summarize the most widely used field-based physical fitness batteries and specific test items for preschool children. A search of the literature in English was undertaken using two major electronics databases, which yielded 76 literatures that met the inclusion and exclusion criteria. These literatures took the quantitative indicators of physical fitness as the outcome variables in 3-6-year-old children. This review found that of these 76 literatures analyzed, 71.1% came from Europe and 89.5% were published after 2010. The results showed six physical fitness test batteries, with the assessing FITness in PREschoolers (PREFIT) battery is the most widely used, and specific test items such as body mass index (BMI), standing long jump, handgrip, one-leg stance, sit and reach, 20 m shuttle run test (SRT)-PREFIT, and 4 × 10 m SRT are widely used in corresponding components. Therefore, we recommend that an international standard for some specific test items should be developed for preschool children to facilitate more widespread adoption and promote physical fitness assessment for preschool children.

Risk Factors of Sports-Related Injury in School-Aged Children and Adolescents: A Retrospective Questionnaire Survey.

Studies conducting quantitative surveys in school-aged children and adolescents help identify sports-related risk factors for acute and overuse injuries are scarce. This study aimed to quantify the risk factors for sports-related injury in school-aged children and adolescents by school categories. University students (n = 484) retrospectively recalled their sports experiences and related injuries in a questionnaire according to the following school categories: lower elementary school (LE), upper elementary school (UE), junior high school (JH), and high school (H). Both sports-related acute and overuse injuries were recorded. After adjusting various covariates, weekly hours in sports were identified as a significant risk factor in LE and UE. The interaction of weekly hours in sports and sports specialization was significant in LE and UE, suggesting that early specialization would be a risk factor in lower school categories. In JH and H, female sex, high-level competition, and injury experienced in a previous school category were significantly related to sports-related injuries. In conclusion, weekly hours in sports, high-level competitions, previous injury experience, and sex were confirmed as risk factors in specific school categories. Most identified risk factors are modifiable, suggesting that sports-related injuries can be prevented in school-aged children and adolescents.

Sports activities at a young age decrease hypertension risk-The J-Fit+ study.

This study aimed to assess (1) blood pressure between young, current athletes, and non-athletes early in life; (2) hypertension prevalence between former athletes and the general population later in life; and (3) understand the mechanisms between exercise training and hypertension risks in the form of DNA methylation. Study 1: A total of 354 young male participants, including current athletes, underwent blood pressure assessment. Study 2: The prevalence of hypertension in 1269 male former athletes was compared with that in the Japanese general population. Current and former athletes were divided into three groups: endurance-, mixed-, and sprint/power-group. Study 3: We analyzed the effect of aerobic- or resistance-training on DNA methylation patterns using publicly available datasets to explore the possible underlying mechanisms. In young, current athletes, the mixed- and sprint/power-group exhibited higher systolic blood pressure, and all groups exhibited higher pulse pressure than non-athletes. In contrast, the prevalence of hypertension in former athletes was significantly lower in all groups than in the general population. Compared to endurance-group (reference), adjusted-hazard ratios for the incidence of hypertension among mixed- and sprint/power-group were 1.24 (0.87-1.84) and 1.50 (1.04-2.23), respectively. Moreover, aerobic- and resistance-training commonly modified over 3000 DNA methylation sites in skeletal muscle, and these were suggested to be associated with cardiovascular function-related pathways. These findings suggest that the high blood pressure induced by exercise training at a young age does not influence the development of future hypertension. Furthermore, previous exercise training experiences at a young age could decrease the risk of future hypertension.

Inhibition of BCL2A1 by STAT5 inactivation overcomes resistance to targeted therapies of FLT3-ITD/D835 mutant AML.

Tyrosine kinase inhibitors (TKIs) are established drugs in the therapy of FLT3-ITD mutated acute myeloid leukemia (AML). However, acquired mutations, such as D835 in the tyrosine kinase domain (FLT3-ITD/D835), can induce resistance to TKIs. A cap analysis gene expression (CAGE) technology revealed that the gene expression of BCL2A1 transcription start sites was increased in primary AML cells bearing FLT3-ITD/D835 compared to FLT3-ITD. Overexpression of BCL2A1 attenuated the sensitivity to quizartinib, a type II TKI, and venetoclax, a selective BCL2 inhibitor, in AML cell lines. However, a type I TKI, gilteritinib, inhibited the expression of BCL2A1 through inactivation of STAT5 and alleviated TKI resistance of FLT3-ITD/D835. The combination of gilteritinib and venetoclax showed synergistic effects in the FLT3-ITD/D835 positive AML cells. The promoter region of BCL2A1 contains a BRD4 binding site. Thus, the blockade of BRD4 with a BET inhibitor (CPI-0610) downregulated BCL2A1 in FLT3-mutated AML cells and extended profound suppression of FLT3-ITD/D835 mutant cells. Therefore, we propose that BCL2A1 has the potential to be a novel therapeutic target in treating FLT3-ITD/D835 mutated AML.

Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs.

Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment.

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.

Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition.

Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation (OxPhos) for survival, and they continually adapt to fluctuations in nutrient and oxygen availability in the bone marrow (BM) microenvironment. We investigated how the BM microenvironment affects the response to OxPhos inhibition in AML by using a novel complex I OxPhos inhibitor, IACS-010759. Cellular adhesion, growth, and apoptosis assays, along with measurements of expression of mitochondrial DNA and generation of mitochondrial reactive oxygen species indicated that direct interactions with BM stromal cells triggered compensatory activation of mitochondrial respiration and resistance to OxPhos inhibition in AML cells. Mechanistically, inhibition of OxPhos induced transfer of mitochondria derived from mesenchymal stem cells (MSCs) to AML cells via tunneling nanotubes under direct-contact coculture conditions. Inhibition of OxPhos also induced mitochondrial fission and increased functional mitochondria and mitophagy in AML cells. Mitochondrial fission is known to enhance cell migration, so we used electron microscopy to observe mitochondrial transport to the leading edge of protrusions of AML cells migrating toward MSCs. We further demonstrated that cytarabine, a commonly used antileukemia agent, increased mitochondrial transfer of MSCs to AML cells triggered by OxPhos inhibition. Our findings indicate an important role of exogenous mitochondrial trafficking from BM stromal cells to AML cells as well as endogenous mitochondrial fission and mitophagy in the compensatory adaptation of leukemia cells to energetic stress in the BM microenvironment.

Sports Specialization and Sports-Related Injuries in Japanese School-Aged Children and Adolescents: A Retrospective Descriptive Study.

Although early sports specialization is associated with sports-related injuries, relevant quantitative studies on young non-elite athletes, the majority of sports participants, are scarce. We described sports specialization time points and the characteristics of sports-related injuries. Undergraduate students at a university in Japan (n = 830) recalled their history of sports participation from elementary to high school and sports-related injuries in a self-administered questionnaire. Of 570 valid respondents, 486 (85%) engaged in sports at least once. Significantly more respondents played multiple sports in upper elementary school (30%) than in other school categories (1-23%). In junior high and high schools, 90% and 99% played only one sport, respectively. Of the 486 respondents who played sports, 263 (54%) had experienced acute or overuse injuries. The proportion of injured participants significantly differed by school category: lower elementary school (4%), upper elementary school (21%), junior high (35%), and high school (41%). The proportions of acute or overuse injuries in males were higher than those in females. In conclusion, this study clarified a slight variation in sports items, particularly in junior high and high schools, which demonstrates 13 years as the age of beginning specialization in a single sport. More than half of the non-elite athletes experienced sports-related injuries. Injuries were frequently observed in males and those in junior high and high schools.