Characteristics of upper limb joint mechanics with increased cane dependence during walking.

[Purpose] This study investigated the effects of differences in cane dependence on the mechanical work at the shoulder, elbow, and wrist joints during walking. [Participants and Methods] Fifteen volunteers participated in this study (mean ± standard deviation [SD] age: 24.9 ± 2.7 years, height: 1.73 ± 0.04 m, and body mass: 68.5 ± 8.9 kg). The participants walked under three conditions: (1) without a cane, (2) with a cane at 10% body weight (BW), and (3) with a cane at 20% BW. The shoulder, elbow, and wrist joint work was calculated to evaluate the mechanical load. [Results] The results indicated a significant interaction between load conditions and positive joint work, as well as between load conditions and negative joint work. The positive work in the shoulder and elbow joints significantly increased in the 20% BW condition compared to that in the 10% BW condition. [Conclusion] Increased cane dependence did not uniformly increase the positive and negative work of the shoulder, elbow, and wrist joints. Increased cane dependence during walking increases energy generation in the shoulder and elbow joints, which can result in adverse musculoskeletal strain on the shoulder and elbow joints.

Which is superior in improving the performance of short-distance sprints starting in a lateral direction, forward- or false-step technique?

When athletes in ball game sports start sprinting in the forward direction from a parallel stance, they commonly use the forward- and false-step techniques. Previous studies focusing on the performance of short-distance sprints starting in the forward direction have demonstrated that the false-step technique is superior to the forward-step technique. Although athletes start sprinting in various directions based on relevant visual cues, such as movements of the ball or the opponent players, the effectiveness of each technique for starting a sprint in the other direction is still unclear. This study aims to clarify the effectiveness of each technique in improving the performance of the short-distance sprint starting in the lateral direction. In this study, 20 athletes started 5-m sprints in the right direction from the parallel stance using either of these two techniques. Kinematic and kinetic analyses were performed from movement initiation to the flight phase after the second step in the sprinting direction. The average and terminal sprint velocities throughout this range were larger in the forward-step technique (p = 0.039 and 0.003), indicating its superiority in traveling and accelerating performance. The change of sprint velocity in the initial phase until the contact of the first step in the sprinting direction was smaller in the false-step technique (p < 0.001), although this phase included "false step." These results indicate that the forward-step technique is superior in sprints starting in the lateral direction, and the advantage results from greater acceleration in the initial phase immediately after movement initiation. These findings imply the sprint-directional dependence of the relative superiority of these techniques, providing an impetus for athletes and coaches to consider and establish the effective training and coaching methods of short-distance sprints.

The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy.

Skeletal muscle atrophy and the inhibition of muscle regeneration are known to occur as a natural consequence of aging, yet the underlying mechanisms that lead to these processes in atrophic myofibers remain largely unclear. Our research has revealed that the maintenance of proper mitochondrial-associated endoplasmic reticulum membranes (MAM) is vital for preventing skeletal muscle atrophy in microgravity environments. We discovered that the deletion of the mitochondrial fusion protein Mitofusin2 (MFN2), which serves as a tether for MAM, in human induced pluripotent stem (iPS) cells or the reduction of MAM in differentiated myotubes caused by microgravity interfered with myogenic differentiation process and an increased susceptibility to muscle atrophy, as well as the activation of the Notch signaling pathway. The atrophic phenotype of differentiated myotubes in microgravity and the regenerative capacity of Mfn2-deficient muscle stem cells in dystrophic mice were both ameliorated by treatment with the gamma-secretase inhibitor DAPT. Our findings demonstrate how the orchestration of mitochondrial morphology in differentiated myotubes and regenerating muscle stem cells plays a crucial role in regulating Notch signaling through the interaction of MAM.

Optimal degrees of freedom of the lower extremities for human walking and running.

Determining the degrees of freedom (DOF) of the linked rigid-body model, representing a multi-body motion of the human lower extremity, is one of the most important procedures in locomotion analysis. However, a trade-off exists between the quality of data fitting and the generalizability of the model. This study aimed to determine the optimal DOF of the model for the lower extremities that balance the goodness-of-fit and generalizability of the model during walking and running using Akaike's information criterion (AIC). Empirically obtained kinematic data for the lower extremities during walking and running were fitted by models with 9, 18, or 22 DOF. The relative quality of these models was assessed using their bias-corrected AIC (cAIC) value. A significant simple main effect of the model was found on the cAIC value for both walking and running conditions. Pairwise comparisons revealed that the cAIC value of the 18-DOF model was significantly smaller than that of the 9-DOF (walking: p < 0.001, running: p = 0.010) and 22-DOF (walking: p < 0.001, running: p < 0.001) models. These findings suggest that the 18-DOF model is optimal for representing the lower extremities during walking and running, in terms of goodness-of-fit and generalizability.

Eosinophil-derived galectin-10 upregulates matrix metalloproteinase expression in bullous pemphigoid blisters.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease in which abundant eosinophils accumulate in the blisters. Galectin-10 abounds in the cytoplasm of eosinophils and is released as a result of eosinophil extracellular trap cell death (EETosis). OBJECTIVE: To identify EETosis and the pathological roles of galectin-10 in BP. METHODS: EETosis and galectin-10 in BP blisters were confirmed by immunofluorescence and transmission electron microscopy. The concentrations of galectin-10 in serum and blister fluid from BP patients were studied by ELISA. The matrix metalloproteinase (MMP) expression in BP blisters was immunohistochemically compared to that in healthy controls. As an in vitro assay, normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) were stimulated with galectin-10, followed by MMP expression measurement by real-time PCR and ELISA. The signaling pathways activated by galectin-10 were studied using Western blotting and confirmed by inhibition assays. RESULTS: Galectin-10-containing eosinophil infiltration and the extracellular deposition of major basic protein were observed in BP blisters. The ultrastructural characteristics of tissue eosinophils indicated piecemeal degranulation and EETosis. In the BP patients, the concentration of galectin-10 was higher in the blister fluid than in the serum. Several types of MMPs were upregulated in BP blisters. Galectin-10 upregulated the production of MMPs through the pathways of p38 MAPK, ERK and JNK in NHEKs and NHDFs. CONCLUSION: In the BP blisters, the eosinophils underwent EETosis and released galectin-10. Galectin-10 might contribute to BP blister formation through the production of MMPs by keratinocytes and fibroblasts.

Autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia is safe but poses challenges for long-term maintenance of molecular remission: Results of the Auto-Ph17 study.

Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto-PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34+ cells was harvested in all five patients. No patient died within 100 days after auto-PBSCT, and no unexpected serious adverse events were observed. Although 1-year event-free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389-1088 days) after auto-PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto-PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto-PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long-term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long-term molecular remission.

Extra Eyelid-Derived Muscle Stem Cells.

Skeletal muscle stem cells (MuSCs) have been proposed as suitable candidates for cell therapy to muscular disorders since they exhibit a good capacity for myogenic regeneration. However, for better therapeutic outcomes, it is necessary to isolate human MuSCs from a suitable tissue source that possess high myogenic differentiation. In this context, isolated CD56+CD82+ cells from extra eyelid tissues were tested in vitro myogenic differentiation potential. Primary human myogenic cells derived from extra eyelids including orbicularis oculi, might be good candidates for human muscle stem cell-based research.

Competitive-Level Differences in Trunk and Foot Kinematics of Underwater Undulatory Swimming.

The foot and trunk kinematics could be associated with horizontal velocity during underwater undulatory swimming (UUS). This study aimed to compare the foot and trunk kinematic parameters during UUS between faster and slower swimmers. The three-dimensional coordinates of the markers were collected during 15 m UUS for 13 swimmers. Participants were divided into two groups based on their horizontal UUS velocity. The range of motion of the lower waist was greater for the faster swimmers than for the slower swimmers; however, no group differences were found for the foot orientation angle. Both the maximum flexion and extension angular velocities of the lower waist and maximum extension angular velocity of the chest were greater for faster swimmers than for slower swimmers. The toe vertical velocity during upward and downward kicks and horizontal displacement per kick were greater for the faster swimmers than for the slower swimmers, whereas no group difference was found for kick frequency. The increase in the long horizontal displacement per kick could be explained by the increase in vertical velocity of the great toes due to the increased trunk angular velocity. These results indicate that faster swimmers performed the UUS with greater trunk angular velocity.

Impact of HLA Epitope Matching on Outcomes After Unrelated Bone Marrow Transplantation.

The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The number of EMM in recipient-donor pairs in our study population ranged from 0 to 37 in HLA class I (median, 0) and 0 to 60 in HLA class II (median, 1). In addition to the known high-risk mismatch patterns in the Japanese cohort, HLA-C EMM in the GVH direction was associated with a significantly higher risk for grade III-IV aGVHD, leading to a higher risk of non-relapse mortality and lower overall survival (compared with HLA-C matched patients, HR 1.67, 95% CI 1.44-1.95; HR 1.39, 95% CI 1.25-1.54; HR 1.20, 95% CI 1.10-1.30, respectively). HLAMM-based epitope matching might be useful for identifying patients who are at high risk for serious complications after HSCT from HLA mismatched unrelated donors.

Tceal5 and Tceal7 Function in C2C12 Myogenic Differentiation via Exosomes in Fetal Bovine Serum.

The proliferation and differentiation of skeletal muscle cells are usually controlled by serum components. Myogenic differentiation is induced by a reduction of serum components in vitro. It has been recently reported that serum contains not only various growth factors with specific actions on the proliferation and differentiation of myogenic cells, but also exogenous exosomes, the function of which is poorly understood in myogenesis. We have found that exosomes in fetal bovine serum are capable of exerting an inhibitive effect on the differentiation of C2C12 myogenic cells in vitro. In this process of inhibition, the downregulation of Tceal5 and Tceal7 genes was observed. Expression of these genes is specifically increased in direct proportion to myogenic differentiation. Loss- or gain- of function studies with Tceal5 and Tceal7 indicated that they have the potential to regulate myogenic differentiation via exosomes in fetal bovine serum.