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Gait is associated with an important risk factor of falls in the elderly. It is important to find differences of quantitative gait variables between fallers and non-fallers. The aim of this study was to investigate gait patterns in elderly fallers and non-fallers. Thirty-eight fallers and 38 non-fallers of similar age and height participated in this study. Subjects walked across the GaitRite walkway at self-selected comfortable speeds. Spatio-temporal gait variables were measured to characterize gait patterns. Kinetic variables were derived from normalized vertical ground reaction force (GRF). Independent t-tests were performed to compare the fallers with the non-fallers. The fallers walked more slowly with shorter steps and more variable step times than the non-fallers (p< 0.05). The fallers showed a longer stance phase with increased double-limb support than the non-fallers (p< 0.05). The times to reach maximal weight acceptance and mid-stance of the fallers were significantly longer than those of the non-fallers (p< 0.05). These results suggest that spatio-temporal variables and GRF variables would be useful for distinguishing prospective fallers from non-fallers among the elderly.

ALS is a fatal neurodegenerative disorder of motor neurons leading to progressive atrophy and weakness of muscles. Some of the earliest pathophysiological changes occur at the level of skeletal muscle and the neuromuscular junction. We previously identified distinct mRNA patterns, including members of the Smad and TGF-β family, that emerge in muscle tissue at the earliest (pre-clinical) stages. These patterns track disease progression in the mutant SOD1 mouse and are present in human ALS muscle. Because miRNAs play a direct regulatory role in mRNA expression, we hypothesized in this study that there would be distinct miRNA patterns in ALS muscle appearing in early stages that could track disease progression. We performed next-generation miRNA sequencing on muscle samples from G93A SOD1 mice at early (pre-clinical) and late (symptomatic) stages, and identified distinct miRNA patterns at both stages with some overlap. An Ingenuity Pathway Analysis predicted effects on a number of pathways relevant to ALS including TGF-β signaling, axon guidance signaling, and mitochondrial function. A subset of miRNAs was validated in the G93A SOD1 mouse at four stages of disease, and several appeared to track disease progression, including miR-206. We assessed these miRNAs in a large cohort of human ALS and disease control samples and found that some had similar changes but were not specific for ALS. Surprisingly, miR-206 levels did not change overall compared to normal controls, but did correlate with changes in strength of the muscle biopsied. In summary, we identified distinct miRNA patterns in ALS muscle that reflected disease stage which could potentially be used as biomarkers of disease activity.

Distal axonopathy is a recognized pathological feature of amyotrophic lateral sclerosis (ALS). In the peripheral nerves of ALS patients, motor axon loss elicits a Wallerian‐like degeneration characterized by denervated Schwann cells (SCs) together with immune cell infiltration. However, the pathogenic significance of denervated SCs accumulating following impaired axonal growth in ALS remains unclear. Here, we analyze SC phenotypes in sciatic nerves of ALS patients and paralytic SOD1G93A rats, and identify remarkably similar and specific reactive SC phenotypes based on the pattern of S100β, GFAP, isolectin and/or p75NTR immunoreactivity. Different subsets of reactive SCs expressed colony‐stimulating factor‐1 (CSF1) and Interleukin‐34 (IL‐34) and closely interacted with numerous endoneurial CSF‐1R‐expressing monocyte/macrophages, suggesting a paracrine mechanism of myeloid cell expansion and activation. SCs bearing phagocytic phenotypes as well as endoneurial macrophages expressed stem cell factor (SCF), a trophic factor that attracts and activates mast cells through the c‐Kit receptor. Notably, a subpopulation of Ki67+ SCs expressed c‐Kit in the sciatic nerves of SOD1G93A rats, suggesting a signaling pathway that fuels SC proliferation in ALS. c‐Kit+ mast cells were also abundant in the sciatic nerve from ALS donors but not in controls. Pharmacological inhibition of CSF‐1R and c‐Kit with masitinib in SOD1G93A rats potently reduced SC reactivity and immune cell infiltration in the sciatic nerve and ventral roots, suggesting a mechanism by which the drug ameliorates peripheral nerve pathology. These findings provide strong evidence for a previously unknown inflammatory mechanism triggered by SCs in ALS peripheral nerves that has broad application in developing novel therapies.

BACKGROUND: The sitting in an awkward posture for a prolonged time may lead to spinal or musculoskeletal disease. It is important to investigate the joint loads at spine while sitting.OBJECTIVE: The purpose of this study was to investigate the joint moment and antero-posterior (AP) reaction force at cervico-thoracic and lumbosacral joint for various sitting postures.METHODS: Twenty healthy males participated in this study. Six sitting postures were defined from three spinal curvatures (slump, flat, and lordosis) and two arm postures (arms-on-chest and arms-forward). Kinematic and kinetic data were measured in six sitting postures from which joint moment and AP reaction force were calculated by inverse dynamics.RESULTS: In the cervico-thoracic joint, joint moment and AP reaction force were greater in slump than the flat and lordosis postures (p< 0.001) and also in arms-forward posture compared to arms-on-chest posture. In the lumbosacral joint, joint moment and AP reaction force were greater in slump than flat and lordotic posture (p< 0.001) but there was no difference between different arm postures. The joint loads (moment and AP reaction force) at the cervico-thoriacic joint were closely related to the head flexion angle (r> 0.86) while those at the lumbosacral joint were correlated to the trunk flexion angle (r> 0.77). In slump posture, the joint moments were close to or over the extreme of the daily life such as sit-to-stand and walking. Consequently, if the slump is continued for a long time, it may cause pain and diseases at the cervico-thoracic and lumbosacral joints.CONCLUSIONS:The results of the study indicated that the lordosis or flat would be better spinal postures. Also, keeping arms close to body would be desirable to reduce joint loads.

BACKGROUND: It is important to quantitatively assess tremor for accurate diagnosis and evaluation of the response to interventions in patients with essential tremor (ET). OBJECTIVE: The purpose of this study was to investigate the relationship between quantitative measures of postural tremor and clinical rating scale in patients with ET. METHODS: 18 ET patients performed a postural tremor task that required them to hold their arms outstretched parallel to the floor while wearing a gyro sensor based measurement system. The time domain variables were derived from the sensor signals. Additionally, the frequency domain variables were derived from the power spectrum of the angular velocity signal. Spearman correlation analysis was employed in the relationship between the variables and clinical score. RESULTS: The RMS angular velocity of roll and yaw directions at the hand joint were strongly correlated with the clinical rating scale (r = 0.7, p < 0.01). Similarly, the peak power of roll and yaw directions at the hand joint were moderately correlated with the clinical rating scale (r = 0.61 and r = 0.67, p < 0.01). In contrast, no significant correlation coefficients were observed in the peak frequency (p > 0.05). CONCLUSION: These results indicate that hand tremor of roll and yaw directions are more associated with assessment of severity of ET compared to other joints. This study suggests that quantitative measurements of postural tremor should be considered as tremor directionality as well as attachment location.

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