The relationship between children's somatotypes, motor examination results, and motor skills: assessing 6- to 10-year-olds.

[Purpose] Childhood motor disorders and obesity are major health problems and concerns in children today. We performed a physical examination to test the motor system and motor ability of elementary school children based on their body types. [Participants and Methods] The obesity levels of 161 elementary school students aged six to ten were calculated based on the gender, age, and standard weight for each height category to classify them into somatotype groups, and analyze the relationships among the results of four motor examination items, Physical Fitness Test, and body composition analysis for two groups. [Results] More obese children were unable to reach the floor while performing a standing forward bend compared to non-obese children. In addition, a significant difference was found in the assessment of motor performance while performing side-to-side jumping, and obese children showed better values. Many endomorphic children were also unable to touch the floor with their hands when performing the standing forward bend. Among the items from a physical fitness test, the side-to-side hops revealed significant differences. There were no somatotype-related differences in the results of the body composition analysis. [Conclusion] In children aged six to ten years, somatotype differences were not associated with motor skill or body composition.

ZBP1 governs the inflammasome-independent IL-1α and neutrophil inflammation that play a dual role in anti-influenza virus immunity.

Influenza A virus (IAV) triggers the infected lung to produce IL-1 and recruit neutrophils. Unlike IL-1ß, however, little is known about IL-1α in terms of its mechanism of induction, action and physiological relevance to the host immunity against IAV infection. In particular, whether Z-DNA-binding protein 1 (ZBP1), a key molecule for IAV-induced cell death, is involved in the IL-1α induction, neutrophil infiltration and the physiological outcome has not been elucidated. Here, we show in a murine model that the IAV-induced IL-1α is mediated solely by ZBP1, in an NLRP3-inflammasome-independent manner, and is required for the optimal IL-1ß production followed by the formation of neutrophil extracellular traps (NETs). During IAV infection, ZBP1 displays a dual role in anti-IAV immune responses mediated by neutrophils, resulting in either protective or pathological outcomes in vivo. Thus, ZBP1-mediated IL-1α production is the key initial step of IAV-infected NETs, regulating the duality of the consequent lung inflammation.

Ectopic Expression Induces Abnormal Somatodendritic Distribution of Tau in the Mouse Brain.

Tau is a microtubule (MT)-associated protein that is localized to the axon. In Alzheimer's disease, the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. To investigate how this mislocalization occurs, we recently developed immunohistochemical tools that can separately detect endogenous mouse and exogenous human tau with high sensitivity, which allows us to visualize not only the pathological but also the pre-aggregated tau in mouse brain tissues of both sexes. Using these antibodies, we found that in tau-transgenic mouse brains, exogenous human tau was abundant in dendrites and somata even in the presymptomatic period, whereas the axonal localization of endogenous mouse tau was unaffected. In stark contrast, exogenous tau was properly localized to the axon in human tau knock-in mice. We tracked this difference to the temporal expression patterns of tau. Endogenous mouse tau and exogenous human tau in human tau knock-in mice exhibited high expression levels during the neonatal period and strong suppression into the adulthood. However, human tau in transgenic mice was expressed continuously and at high levels in adult animals. These results indicated the uncontrolled expression of exogenous tau beyond the developmental period as a cause of mislocalization in the transgenic mice. Superresolution microscopic and biochemical analyses also indicated that the interaction between MTs and exogenous tau was impaired only in the tau-transgenic mice, but not in knock-in mice. Thus, the ectopic expression of tau may be critical for its somatodendritic mislocalization, a key step of the tauopathy.SIGNIFICANCE STATEMENT Somatodendritic localization of tau may be an early step leading to the neuronal degeneration in tauopathies. However, the mechanisms of the normal axonal distribution of tau and the mislocalization of pathological tau remain obscure. Our immunohistochemical and biochemical analyses demonstrated that the endogenous mouse tau is transiently expressed in neonatal brains, that exogenous human tau expressed corresponding to such tau expression profile can distribute into the axon, and that the constitutive expression of tau into adulthood (e.g., human tau in transgenic mice) results in abnormal somatodendritic localization. Thus, the expression profile of tau is tightly associated with the localization of tau, and the ectopic expression of tau in matured neurons may be involved in the pathogenesis of tauopathy.

Intestinal CX3C chemokine receptor 1(high) (CX3CR1(high)) myeloid cells prevent T-cell-dependent colitis.

Adequate activation of CD4(+) T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4(+) T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX(3)C chemokine receptor 1(high) (CX(3)CR1(high)) CD11b(+) CD11c(+) cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4(+) T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX(3)CR1(high) CD11b(+) CD11c(+) cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX(3)CR1(high) CD11b(+) CD11c(+) cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis.

Association between occlusal force and physical functions in preschool children: a comparison of males and females.

[Purpose] To determine and compare changes over time in the physical strength of male and female children aged 4-5 years by measuring physical functions such as occlusal forces. [Subjects and Methods] The occlusal force, weight, height, grip strength, standing long jump, ball throwing, timed up and go (TUG), and the 25-m run time were measured of 331 children to determine their physical strength. All the children understood and were capable of completing all tests. [Results] Occlusal force among male infants significantly correlated with all items except ball throwing. Stepwise multiple regression analysis independently associated occlusal force with grip strength. In contrast, occlusal force of female infants significantly correlated with all the tested items. Stepwise multiple regression analysis also independently associated occlusal force with grip strength and TUG in females. [Conclusion] Grip strength indicating upper-limb muscle strength correlated with occlusal forces in both male and female children, whereas TUG, balance and walking ability indicating muscle strength of the lower limbs, correlated with items relevant to everyday functions in female infants. These findings show that different factors are involved in the occlusal forces of male and female children.

Effects of Wheelchair Seat-height Settings on Alternating Lower Limb Propulsion With Both Legs.

This study investigated the effects of seat-height settings of wheelchairs with alternating propulsion with both legs. Seven healthy individuals with no orthopedic disease participated. Flexion angles at initial contact (FA-IC) of each joint, range of motion during propulsion period (ROM-PP), and ground reaction force (GRF) were measured using a three dimensional motion capture system and force plates, and compared with different seat-height settings. Statistically significant relationships were found between seat-height and speed, stride length, knee FA-IC, ankle FA-IC, hip ROM-PP, vertical ground reaction force (VGRF), and anterior posterior ground reaction force (APGRF). Speed, hip ROM-PP, VGRF and APGRF increased as the seat-height was lowered. This effect diminished when the seat-height was set below -40 mm. VGRF increased as the seat-height was lowered. The results suggest that the seat-height effect can be attributed to hip ROM-PP; therefore, optimal foot propulsion cannot be achieved when the seat height is set either too high or too low. Efficient foot propulsion of the wheelchair can be achieved by setting the seat height to lower leg length according to a combination of physical characteristics, such as the user's physical functions, leg muscles, and range of motion.

Relationships between the Occlusal Force and Physical/Cognitive Functions of Elderly Females Living in the Community.

[Purpose] The present study, was conducted to examine the occlusal force and physical, cognitive, and attentional functions of elderly females living in the community to evaluate the significance of measuring the occlusal force. [Subjects and Methods] The number of subjects was 104. The Occlusal Force Meter GM10 was used to measure their occlusal force. Their physical functions were assessed using eight examinations, including the 30-second Chair Stand Test, and the cognitive functions of the Mini-Mental State Examination and attention functions of the Trail Making Test. [Results] Significant correlations were noted between the occlusal force and all measurements, except for the results of forward bending in a sitting position. Multiple regression analysis was conducted with the occlusal force as an objective variable, and significant partial correlations were noted with the 30-second Chair Stand Test. [Conclusion] These results suggest that it is necessary to provide the elderly with comprehensive support focusing on maintaining their occlusal force, as a nursing care-prevention measure, to help them continue to live a healthy, independent life.

Verification of the Correlation between Cognitive Function and Lower Limb Muscle Strength for the Community-dwelling Elderly.

[Purpose] The purpose of this study was to evaluate the lower limb muscle strength of the community-dwelling elderly, with or without cognitive decline, using isometric knee extension strength (IKES) and the 30-second chair stand test (CS-30). [Subjects] A total of 306 community-dwelling elderly participated in this study. Assessment items were the CS-30, IKES, Mini-Mental State Examination (MMSE), and Trail-Making Test Part A (TMT-A). [Methods] Participants were divided into three groups according to their MMSE score: cognitive impairment (MMSE ≤ 24), cognitive decline (MMSE 25 to 27), and normal (MMSE ≥ 28). We compared IKES and CS-30 among the three groups. [Results] IKES was not significantly different among the three groups. However, the CS-30 was significantly different among the three groups. Upon further analysis the CS-30 score of each group, when adjusted for age and TMT-A, did not indicate a significant difference. [Conclusion] These results suggest that the lower limb muscle strength of the elderly does not differ with cognitive decline. Moreover, we suggest that when using the CS-30 score as an indicator of lower limb muscle strength attentional function should be taken into account.

Association of adolescent postural tachycardia syndrome classifications with anxiety: a cross sectional study.

BACKGROUND: Postural tachycardia syndrome (POTS), a subset of orthostatic dysregulation, has been reported to be associated with anxiety. POTS can be classified into two forms based on the degree of tachycardia during orthostasis. Reportedly, POTS with decreased orthostatic heart rate increase is associated with suppressed cardiac parasympathetic activity and increased sympathetic activity in the supine position. In this study, the relationship between the two types of POTS and anxiety was evaluated in terms of autonomic function. METHODS: Fifty-two patients (23 male, age 10-15 years) who were diagnosed with POTS at the Department of Pediatrics, Osaka Medical and Pharmaceutical University from 2019 to 2021, completed a standing test and were accordingly classified into a Su group, with tachycardia from the supine position and a low heart rate increase on standing, a SI group, with a high heart rate increase during standing. They then completed the State-Trait Anxiety Scale for Children (STAIC) questionnaire. Autonomic function was assessed by frequency analysis (MemCalc method) based on heart rate, blood pressure changes, heart rate and blood pressure variability during the orthostatic test. RESULTS: Patients in the Su group had higher trait anxiety and state anxiety, lower cardiac parasympathetic activity (RR-HF) in the supine position, and greater variability in cardiac parasympathetic activity during orthostasis than were found for patients in the SI group. The Su group had a greater decrease in cardiac index on standing than that of the SI group. CONCLUSIONS: The Su group results may be partly attributed to chronically low venous return. We also found that patients in the Su group had low parasympathetic activity in the supine position, which may interact with the anxiety-prone characteristics of these patients. Therefore, it seems necessary to consider both physical and psychosomatic treatment approaches for patients with POTS.

Age-specific comparisons in the rate of force development of toe pressure strength and its association with the timed up and go test.

PURPOSE: It has recently been recommended that Rate of Force Development (RFD) be evaluated in addition to maximal muscle strength. There are no studies on RFD of toe pressure strength, and its importance in older adults and the extent to which it is associated with aging needs to be clarified. This study purpose was to examine the association between the RFD of toe pressure strength and timed up and go test (TUG) in an age-specific study. METHODS: This study is a cross-sectional study. Participants in the study included 159 younger adults (26.3 ± 13.1 years, 52% male) and 88 older adults (75.0 ± 6.2 years, 26% male). The RFD of toe pressure strength was determined from the force-time curve obtained during the toe pressure strength assessment, and the ability to exert maximum muscle force in the shortest possible time was assessed. Regression analysis was performed for each group to test the association between RFD of toe pressure strength and TUG by age. RESULTS: Younger adults showed no association between TUG and RFD of toe pressure strength, and significant association between TUG and RFD of toe pressure strength was found only in the older adults (standard regression coefficient = - 0.19, p = 0.048). CONCLUSION: This study showed a significant association between TUG and RFD of toe pressure strength in older adults. These findings show that RFD is one of the functions that should be assessed, particularly in older adults. Furthermore, it was suggested that approaching RFD could improve gait, standing, and sitting movements.

Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase.

The oocytes of vertebrates are typically arrested at metaphase II (mII) by the cytostatic factor Emi2 until fertilization. Regulatory mechanisms in Xenopus Emi2 (xEmi2) are understood in detail but contrastingly little is known about the corresponding mechanisms in mammals. Here, we analyze Emi2 and its regulatory neighbours at the molecular level in intact mouse oocytes. Emi2, but not xEmi2, exhibited nuclear targeting. Unlike xEmi2, separable N- and C-terminal domains of mouse Emi2 modulated metaphase establishment and maintenance, respectively, through indirect and direct mechanisms. The C-terminal activity was mapped to the potential phosphorylation target Tx(5)SxS, a destruction box (D-box), a lattice of Zn(2+)-coordinating residues and an RL domain. The minimal region of Emi2 required for its cytostatic activity was mapped to a region containing these motifs, from residue 491 to the C terminus. The cytostatic factor Mos-MAPK promoted Emi2-dependent metaphase establishment, but Mos autonomously disappeared from meiotically competent mII oocytes. The N-terminal Plx1-interacting phosphodegron of xEmi2 was apparently shifted to within a minimal fragment (residues 51-300) of mouse Emi2 that also contained a calmodulin kinase II (CaMKII) phosphorylation motif and which was efficiently degraded during mII exit. Two equimolar CaMKII gamma isoform variants were present in mII oocytes, neither of which phosphorylated Emi2 in vitro, consistent with the involvement of additional factors. No evidence was found that calcineurin is required for mouse mII exit. These data support a model in which mammalian meiotic establishment, maintenance and exit converge upon a modular Emi2 hub via evolutionarily conserved and divergent mechanisms.

Domains of the Kihon Checklist Associated with Prefrailty among Community-Dwelling Older Adults.

BACKGROUND: Various functions are involved in prefrailty. However, no studies have examined more relevant functions. Therefore, this study examined the domains of the Kihon Checklist (KCL) associated with prefrailty by comparing them to robustness measures, using the KCL to comprehensively assess life-related functions in community-dwelling older adults. METHODS: The 194 (mean age, 75±6 years) participants were community-dwelling older adults. Their robustness and preferences were assessed using the Japanese Cardiovascular Health Study criteria. Comprehensive life-related functions were assessed using the KCL, and each physical function was measured. RESULTS: The main KCL characteristics associated with robustness and prefrailty were physical function (odds ratio [OR]=1.83; 95% confidence interval [CI], 1.17-2.88), nutritional status (OR=8.16; 95% CI, 2.96-22.48), and depressed mood (OR=3.46; 95% CI, 1.76-6.79). In particular, older adults had difficulty moving, including climbing stairs and getting up from a chair, which suggested a strong fear of falling. The participants also reported psychological characteristics such as low life fulfillment, a low sense of self-usefulness, and a strong sense of boredom. CONCLUSIONS: Prefrail individuals were characterized by poor physical function and nutritional status, as well as depressive mood. Prefrailty may be prevented or improved by approaches to improve physical function and fear of falling in addition to psychological interventions that encourage activity and a sense of self-usefulness.

In vivo fluorescence imaging of bone-resorbing osteoclasts.

Osteoclasts are giant polykaryons responsible for bone resorption. Because an enhancement or loss of osteoclast function leads to bone diseases such as osteoporosis and osteopetrosis, real-time imaging of osteoclast activity in vivo can be of great help for the evaluation of drugs. Herein, pH-activatable chemical probes BAp-M and BAp-E have been developed for the detection of bone-resorbing osteoclasts in vivo. Their acid dissociation constants (pK(a)) were determined as 4.5 and 6.2 by fluorometry in various pH solutions. These pK(a) values should be appropriate to perform selective imaging of bone-resorbing osteoclasts, because synthesized probes cannot fluoresce intrinsically at physiological pH and the pH in the resorption pit is lowered to about 4.5. Furthermore, BAp-M and BAp-E have a bisphosphonate moiety that enabled the probes to localize on bone tissues. The hydroxyapatite (HA) binding assay in vitro was, therefore, performed to confirm the tight binding of the probes to the bone tissues. Our probes showed intense fluorescence at low pH values but no fluorescence signal under physiological pH conditions on HA. Finally, we applied the probes to in vivo imaging of osteoclasts by using intravital two-photon microscopy. As expected, the fluorescence signals of the probes were locally observed between the osteoclasts and bone tissues, that is, in resorption pits. These results indicate that our pH-activatable probes will prove to be a powerful tool for the selective detection of bone-resorbing osteoclasts in vivo, because this is the first instance where in vivo imaging has been conducted in a low-pH region created by bone-resorbing osteoclasts.

Effects of Long-Term Use of Insoles with a Toe-Grip Bar on the Balance, Walking, and Running of Preschool Children: A Randomized Controlled Trial.

This randomized controlled study is aimed at investigating the effects of long-term use of insoles with a toe-grip bar on the balance, walking, and running of preschool children. Fifty-two preschool children were randomly assigned to an intervention group or control group. Children included in the intervention group wore shoes with insoles that had a toe-grip bar, and those in the control group wore shoes with regular insoles without a toe-grip bar for 4 weeks while they were at school. The center of gravity sway (total trajectory length and envelope area), walking parameters (walking speed, cadence, stride length, step length, stance time, and swing time), and time to run 25 m were measured before and after the intervention. The 25 m running time of the intervention group was significantly improved after the intervention (F = 5.66; p < 0.05). This study suggests that insoles with a toe-grip bar may contribute to improvements in the running of preschool children.

Multiple brain abscesses with good prognosis in an infant with cyanotic congenital heart disease: a case report.

BACKGROUND: Brain abscesses are relatively rare, but they are a potentially life-threatening condition. Predictive factors for poor outcome are a young age and the presence of multiple abscesses. We report a case of a 15-month-old girl with cyanotic congenital heart disease who developed multiple brain abscesses caused by Streptococcus intermedius. The patient was treated with a combination of surgical aspiration and antimicrobial therapy without apparent neurological sequelae. To the best of our knowledge, this is the youngest such patient to have been reported in the literature. We explore the possible causes of her good outcome. CASE PRESENTATION: At the age of 15 months, the Japanese patient initially was presented to our hospital with transient eye deviation to the left and vomiting. In a blood examination, her white blood cell count (12,720 per mm3 with a left shift) and C-reactive protein level (1.23 mg/ml) were slightly elevated. Magnetic resonance imaging of the brain showed three mass lesions. These were 1.5-cm, 1.9-cm, and 1.2-cm rim-enhancing lesions with extensive surrounding edema. Brain abscesses were diagnosed, and vancomycin (50 mg every 12 hours) and meropenem (40 mg every 8 hours) were started empirically. However, because each brain abscess was enlarged at 8 days after admission, surgical aspiration was performed at 10 days after admission, and cultures of the aspirated pus grew S. intermedius. Penicillin G (0.7 million units every 4 hours) and ceftriaxone (280 mg every 12 hours), to which this isolate is susceptible, were then administered, and the brain abscesses reduced in size. After 1 month of ceftriaxone and 3 months of penicillin G treatment, all of the brain abscesses disappeared. Apparent neurological sequelae were not observed at 6 months after onset. CONCLUSIONS: A good outcome can be obtained if multiple brain abscesses develop in infancy or early childhood in cases without unconsciousness at admission, meningitis, or sepsis. Appropriate antimicrobial therapy should be started immediately after diagnosis, with surgical aspiration performed to identify the causative pathogen and avoid intraventricular rupture of the brain abscesses.

Distribution of endogenous normal tau in the mouse brain.

Tau is a microtubule-associated protein (MAP) that is localized to the axon. In Alzheimer's disease (AD), the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. While the abnormal aggregated tau has been extensively studied in human patient tissues and animal models of AD, how normal tau localizes to the axon, which would be the foundation to understand how the mis-localization occurs, has not been well studied due to the poor detectability of normal unaggregated tau in vivo. Therefore, we developed immunohistochemical techniques that can detect normal mouse and human tau in brain tissues with high sensitivity. Using these techniques, we demonstrate the global distribution of tau in the mouse brain and confirmed that normal tau is exclusively localized to the axonal compartment in vivo. Interestingly, tau antibodies strongly labeled nonmyelinated axons such as hippocampal mossy fibers, while white matters generally exhibited low levels of immunoreactivity. Furthermore, mouse tau is highly expressed not only in neurons but also in oligodendrocytes. With super resolution imaging using the stimulated-depletion microscopy, axonal tau appeared punctate rather than fibrous, indicating that tau decorates microtubules sparsely. Co-labeling with presynaptic and postsynaptic markers revealed that normal tau is not localized to synapses but sparsely distributes in the axon. Taken together, this study reports novel antibodies to investigate the localization and mis-localization of tau in vivo and novel findings of normal tau localization in the mouse brain.

Profiles of Periglomerular Cells in the Olfactory Bulb of Prokineticin Type 2 Receptor-deficient Mice.

Both prokineticin receptor 2 (pkr2) and prokineticin 2 (pk2) gene-deficient mice have hypoplasia of the main olfactory bulb (MOB). This hypoplasia has been attributed to disruption of the glomerulus that is caused by loss of afferent projection from olfactory sensory neurons (OSN), and to the impaired migration of granule cells, a type of interneuron. In the present study, we examined whether migration of the second type of interneuron, periglomerular cells (PGC), is dependent on the pkr2 expression by observing the localization of distinct subpopulations of PGC: calretinin (CR)-, calbindin (CB)- and tyrosine hydroxylase (TH)-expressing neurons. In the Pkr2-/- mice, the construction of the layered structure of the MOB was partially preserved, with the exception of the internal plexiform layer (IPL) and the glomerular layer (GL). In the outermost layer of the MOB, abundant CR- and CB-immunopositive neurons were observed in the hypoplastic olfactory bulb. In addition, although markedly decreased, TH-immunopositive neurons were also observed in the outermost cell-dense region in the Pkr2-/-. The findings suggest that the migration of PGC to the MOB, as well as the migration from the core to the surface region of the MOB, is not driven by the PK2-PKR2 system.

Dynamic visualization of dendritic cell-antigen interactions in the skin following transcutaneous immunization.

Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC) residing in the skin including Langerhans cells (LC) and dermal dendritic cells (DDC). However, the main obstacle for transcutaneous immunization (TCI) is the effective delivery of the vaccine through the stratum corneum (SC) barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN) and a lipid-based colloidal delivery system (cubosomes) as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP) 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207⁺ DC. No uptake of antigen or any response to immunisation by LC could be detected.