Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series.

Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

Intrinsic Risk Factors for Noncontact Anterior Cruciate Ligament Injury in Young Female Soccer Players: A Prospective Cohort Study.

BACKGROUND: Previous studies have attempted to determine prognostic factors for predicting the occurrence of noncontact anterior cruciate ligament (ACL) injuries. However, studies on risk factors for noncontact ACL injuries in Asian female soccer players are limited. PURPOSE: To identify intrinsic risk factors for noncontact ACL injuries among young female Asian soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study evaluated 145 female Japanese soccer players for potential risk factors for noncontact ACL injury during the preseason medical assessment. In total, 25 variables were examined-including anthropometric data, joint range of motion, muscle flexibility, muscle strength, and balance measurements. Participants were monitored throughout a single season for noncontact ACL injuries diagnosed by physicians. RESULTS: Noncontact ACL injuries occurred in 13 knees of 13 players (9%). Lower hamstring-to-quadriceps ratio (0.44 ± 0.07 vs 0.50 ± 0.10; P = .04), greater knee extension muscle strength (3.2 ± 0.5 vs 2.7 ± 0.5 N·m/kg; P < .01), and longer playing experience (10.8 ± 3 vs 8.1 ± 4.2 years; P = .02) were significantly associated with new-onset noncontact ACL injuries in young female soccer players. No statistically significant between-group differences were found for any other variables. CONCLUSION: New-onset noncontact ACL injury in young female soccer players was significantly associated with lower hamstring-to-quadriceps ratio, greater knee extension muscle strength, and longer soccer experience. These findings will help develop strategies for preventing noncontact ACL injuries among female soccer players.

Implicit learning provides advantage over explicit learning for gait-cognitive dual-task interference.

Dual-task performance holds significant relevance in real-world scenarios. Implicit learning is a possible approach for improving dual-task performance. Analogy learning, utilizing a single metaphor to convey essential information about motor skills, has emerged as a practical method for fostering implicit learning. However, evidence supporting the effect of implicit learning on gait-cognitive dual-task performance is insufficient. This exploratory study aimed to examine the effects of implicit and explicit learning on dual-task performance in both gait and cognitive tasks. Tandem gait was employed on a treadmill to assess motor function, whereas serial seven subtraction tasks were used to gauge cognitive performance. Thirty healthy community-dwelling older individuals were randomly assigned to implicit or explicit learning groups. Each group learned the tandem gait task according to their individual learning styles. The implicit learning group showed a significant improvement in gait performance under the dual-task condition compared with the explicit learning group. Furthermore, the implicit learning group exhibited improved dual-task interference for both tasks. Our findings suggest that implicit learning may offer greater advantages than explicit learning in acquiring autonomous motor skills. Future research is needed to uncover the mechanisms underlying implicit learning and to harness its potential for gait-cognitive dual-task performance in clinical settings.

Motion Capture-based 3-dimensional Measurement of Range of Motion in Patients Undergoing Cervical Laminoplasty.

STUDY DESIGN: A prospective study. OBJECTIVE: To measure 3-dimensional cervical range of motion (ROM) by noninvasive optical tracking-based motion-capture technology in patients undergoing laminoplasty, and to elucidate the postoperative effects of laminoplasty on cervical mobility. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a motion-sparing decompression surgery for degenerative cervical myelopathy. Unlike cervical laminectomy and fusion, the true postoperative impact of laminoplasty on neck motion has not been well studied. METHODS: Participants comprised 25 patients undergoing double-door cervical laminoplasty for degenerative cervical myelopathy in a single center. Maximum flexion/extension, left/right rotation, and left/right side bending were recorded using the motion-capture device preoperatively and 3 months postoperatively. ROMs in 3 orthogonal axes were calculated. Preoperative differences in C2-7 Cobb angles on lateral flexion/extension x-rays were also measured as the radiologic ROM to assess reliability. Preoperative and 1-year postoperative Japanese Orthopaedic Association score, Neck Disability Index [NDI], and Euro-QOL were recorded, and correlations with ROMs were assessed. RESULTS: Preoperative mean (±SD) ROMs for flexion/extension, rotation, and side bending were 90±17, 107±16, and 53±17 degrees, respectively. Although radiologic sagittal ROM measurement showed a smaller range than motion capture, averaging 36±13 degrees, a moderate to strong correlation between radiologic and motion capture values was observed (R=0.57, P=0.003). Preoperative NDI showed a negative correlation with coronal ROM (rho=-0.547, P=0.02). Postoperative ROM showed a significant reduction in rotation (95±16 degrees, P=0.002) but not in flexion/extension or side bending. CONCLUSIONS: Three-dimensional motion-capture analysis allowed reliable measurement of cervical ROM. Rotational ROM was significantly reduced after laminoplasty, showing that cervical kinematics are still significantly altered.

Factors Associated With a Lateral Ankle Sprain in Young Female Soccer Players: A Prospective Cohort Study.

Background: Previous studies have attempted to determine if certain risk factors can predict the occurrence of a lateral ankle sprain (LAS) in female soccer players. Unfortunately, there is limited evidence with regard to risk factors associated with an LAS in female soccer players. Purpose: To identify intrinsic risk factors for an LAS among young female soccer players. Study Design: Cohort study; Level of evidence, 2. Methods: Participants were 161 young female soccer players in Japan who were evaluated for LAS risk factors during a preseason medical assessment. The assessment included anthropometric, joint laxity, joint range of motion, muscle flexibility, muscle strength, and balance measurements. Each athlete's history of LASs was also collected. The participants were monitored during a single-yearseason for LASs, as diagnosed by physicians. Results: There were 26 instances of an LAS in 25 players (15.5%) during the season. Injured players were significantly more likely to have sustained a previous ankle sprain (P = .045) and demonstrated significantly worse balance than their peers without an LAS during the double- and single-leg balance tests (P = .008 for both). Athletes with lower hamstring-to-quadriceps muscle strength ratios were also significantly more likely to sustain an LAS (P = .02). Conclusion: Poor balance, a low hamstring-to-quadriceps ratio, and a history of ankle sprains were associated with an increased risk of LASs in young female soccer players in the current study. These findings may be useful for developing a program to prevent LASs in this population.

Neuropathic pain development and maintenance and its association with motor recovery after cervical spinal cord injury.

BACKGROUND: In our published randomized controlled trial, we revealed that patients with acute ASIA Grade C incomplete cervical spinal cord injury (SCI) who underwent early surgery (within 24 h post-injury) had accelerated motor recovery at six months than those with delayed surgery (>2 weeks post-injury); however, neuropathic pain (NeP) worsened regardless of surgery timing. Here, we conducted post-hoc analyses to intensively assess NeP development and maintenance. METHODS: Of 44 patients (median 64.5 years; three female; early intervention, n = 26), NeP was categorized into at-level and below-level pain and evaluated at  two weeks and one year after injury using the Neuropathic Pain Symptom Inventory (NPSI). We compared the two groups based on background characteristics. A mixed-design analysis of variance with sex as a covariate was conducted to analyze motor recovery and Health-related quality of life (HRQOL) in groups with severe (NPSI ≥ 10) or mild (NPSI < 10) pain. RESULTS: Upper and lower limb motor impairments were comparable between both groups regardless of pain severity. Severe at-level pain remained stable and worsened at one year than mild at-level pain; however, the upper- and lower-limb motor scores and HRQOL had comparable recovery. Background characteristics did not affect severity or time course of NeP. Patients with severe below-level pain demonstrated slower lower-limb motor recovery than those with mild below-level pain, whereas HRQOL improved regardless of pain severity. CONCLUSIONS: Both at-level and below-level NeP developed and persisted relatively early in the course of traumatic SCI with incomplete motor paralysis; their severities worsened over time or remained severe since onset.

Lower hamstring to quadriceps muscle strength ratio and lower body weight as factors associated with noncontact anterior cruciate ligament injury in male American football players: A prospective cohort study.

Background: Previous studies have aimed to determine the use of certain risk factors in predicting the occurrence of noncontact anterior cruciate ligament (ACL) injuries. Unfortunately, evidence regarding noncontact ACL injuries in male American football players is limited. This prospective cohort study aimed to identify intrinsic risk factors for noncontact ACL injury among male American football players. Methods: This study evaluated 152 male American football players in Japan for potential noncontact ACL injury risk factors during a preseason medical assessment, including anthropometric, joint laxity, and flexibility, muscle flexibility, muscle strength, and balance measurements. A total of 25 variables were examined. Participants were monitored during each season for noncontact ACL injury, as diagnosed by physicians. Results: Noncontact ACL injuries occurred in 11 knees of 11 players (prevalence; 7.1 %). Injured players were significantly more likely to have lightweight (P = 0.049). No statistically significant between-group differences were found for any other variables. Participants with a lower hamstring to quadriceps (H/Q) ratio (P = 0.04) were more likely to sustain noncontact ACL injuries. Conclusion: Lower H/Q ratio and lower body weight were significantly associated with new-onset noncontact ACL injury in male American football players. These findings will help develop strategies to prevent noncontact ACL injuries in male American football players.

Effect of dual-task interaction combining postural and visual perturbations on cortical activity and postural control ability.

Previous studies have suggested cortical involvement in postural control in humans by measuring cortical activities and conducting dual-task paradigms. In dual-task paradigms, task performance deteriorates and can be facilitated in specific dual-task settings. Theoretical frameworks explaining these dual-task interactions have been proposed and debated for decades. Therefore, we investigated postural control performance under different visual conditions using a virtual reality system, simultaneously measuring cortical activities with a functional near-infrared spectroscopy system. Twenty-four healthy participants were included in this study. Postural stability and cortical activities after perturbations were measured under several conditions consisting of postural and visual perturbations. The results showed that concurrent visual and postural perturbations could facilitate cortical activities in the supplementary motor area and superior parietal lobe. Additionally, visual distractors deteriorated postural control ability and cortical activation of the supplementary motor area. These findings supported the theoretical framework of the "Cross talk model", in which concurrent tasks using similar neural domains can facilitate these task performances. Furthermore, it indicated that the cortical resource capacity and domains activated for information processing should be considered in experiments involving dual-task paradigms and training.

Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.

The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla. Our findings suggest that oscillatory mechanical interventions could be used to elicit antihypertensive effects.

Risk factors for hamstring strain injury in male college American football players -a preliminary prospective cohort study.

BACKGROUND: Given the frequency of hamstring strain injuries (HSI) among male college American football players, several studies have attempted to determine whether certain risk factors can predict their occurrence. However, no consensus on modifiable risk factors for HSIs in male college American football players has yet been reached to prevent these injuries. This study aimed to clarify risk factors for HSI prospectively in college male American football players. METHODS: A total of 78 male college American football players, whose positions were limited to skill positions, were medically assessed for potential risk factors of HSI. The preseason medical assessment included anthropometric measurements, joint laxity and flexibility, muscle flexibility, muscle strength, and balance ability. RESULTS: HSI occurred in a total of 25 thighs from 25 players (32.1%). Injured players had significantly lower hamstring flexibility (p = 0.02) and hamstring to quadriceps strength ratio (H/Q) (p = 0.047) compared to uninjured players. Additionally, injured players had significantly lower general joint laxity scores, especially for the total (p = 0.04), hip (p = 0.007), and elbow (p = 0.04) scores, compared to uninjured players. CONCLUSIONS: Lower hamstring flexibility, lower hamstring to quadriceps strength ratio, and lower general joint laxity score were identified as risk factors for HSI in male college American football players placed in skill positions. The muscle flexibility and H/Q ratio could be useful in preventing HSI in such players.

Modulation of corticospinal excitability related to the forearm muscle during robot-assisted stepping in humans.

In recent years, the neural control mechanisms of the arms and legs during human bipedal walking have been clarified. Rhythmic leg stepping leads to suppression of monosynaptic reflex excitability in forearm muscles. However, it is unknown whether and how corticospinal excitability of the forearm muscle is modulated during leg stepping. The purpose of the present study was to investigate the excitability of the corticospinal tract in the forearm muscle during passive and voluntary stepping. To compare the neural effects on corticospinal excitability to those on monosynaptic reflex excitability, the present study also assessed the excitability of the H-reflex in the forearm muscle during both types of stepping. A robotic gait orthosis was used to produce leg stepping movements similar to those of normal walking. Motor evoked potentials (MEPs) and H-reflexes were evoked in the flexor carpi radialis (FCR) muscle during passive and voluntary stepping. The results showed that FCR MEP amplitudes were significantly enhanced during the mid-stance and terminal-swing phases of voluntary stepping, while there was no significant difference between the phases during passive stepping. Conversely, the FCR H-reflex was suppressed during both voluntary and passive stepping, compared to the standing condition. The present results demonstrated that voluntary commands to leg muscles, combined with somatosensory inputs, may facilitate corticospinal excitability in the forearm muscle, and that somatosensory inputs during walking play a major role in monosynaptic reflex suppression in forearm muscle.

Usefulness of lysophosphatidylcholine measurement in the cerebrospinal fluid for differential diagnosis of neuropathic pain: Possible introduction into clinical laboratory testing.

BACKGROUND: The differential diagnosis of neuropathic pain, especially discrimination between neuropathic pain caused by spinal canal stenosis (SCS) and neuropathic pain associated with causes other than SCS, is sometimes difficult; however, it is important for surgical application. METHODS: We established a reliable method for measuring lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acids which are known as being pain initiators, using a liquid chromatography-tandem mass spectrometry method, and measured the LPC concentrations in the cerebrospinal fluid (CSF) in patients with SCS (SCS group; n = 76), patients with neuropathic pain caused by non-SCS diseases (Others group; n = 49), and control subjects without pain (control group; n = 92). RESULTS: Both within-run and between-run CV(%) were almost < 10 %, suggesting an enough performance for clinical introduction. The CSF concentrations of LPC (16:0) and LPC (18:0) were higher in the SCS group than those in the Control or Others group; the concentrations of LPC (18:1), LPC (18:2), LPC (20:4), LPC (22:6) levels were higher in the SCS group than those in the control or others group, but they were also higher in the Others group than those in the control group. The areas under the curve in the ROC curve analyses of LPC (18:1) for discriminating between the SCS and control groups, others and control groups, and SCS and others groups were 0.994, 0.860, and 0.869, respectively. CONCLUSIONS: LPC measurement in the CSF is useful for the differential diagnosis of neuropathic pain, especially for surgical decision-making, which is expected for clinical introduction.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

An Advanced Internet of Things System for Heatstroke Prevention with a Noninvasive Dual-Heat-Flux Thermometer.

Heatstroke is a concern during sudden heat waves. We designed and prototyped an Internet of Things system for heatstroke prevention, which integrates physiological information, including deep body temperature (DBT), based on the dual-heat-flux method. A dual-heat-flux thermometer developed to monitor DBT in real-time was also evaluated. Real-time readings from the thermometer are stored on a cloud platform and processed by a decision rule, which can alert the user to heatstroke. Although the validation of the system is ongoing, its feasibility is demonstrated in a preliminary experiment.

Practical guidance to handle missing values in the 25-question Geriatric Locomotive Function Scale (GLFS-25): a simulation study.

OBJECTIVES: Despite the possible large number of missing values on the 25-question Geriatric Locomotive Function Scale (GLFS-25), how we should treat them is unknown. In a simulation study, we investigated how to handle missing values in the GLFS-25. DESIGN, SETTING AND PARTICIPANTS: We used three datasets with different participant characteristics: community dwellers who could walk by themselves, outpatients of orthopaedics owing to pain, and patients who required surgery for total knee replacement or lumbar spinal canal stenosis. OUTCOME MEASURES: The missing items of the datasets were artificially created, and four statistical methods, complete case analysis, multiple imputation, single imputation using individual mean, and single imputation using individual domain average, were compared in terms of bias and mean squared error. Simulation studies were conducted to compare them under varying numbers of participants with missing values (5%-40%) and under varying numbers of missing items of GLFS-25 (4-16). RESULTS: Multiple imputation had the lowest root mean squared error. Complete case analysis showed the largest bias, and the performances of the single imputation were between those methods. The relative performances were similar across the three datasets. The absolute bias of the single imputation was<0.1. The bias and mean squared error of multiple imputation and single imputation were comparable when the number of missing items was less than or equal to eight. CONCLUSIONS: Multiple imputation is preferable, although single imputation using subject average/subject domain average can be used with practically negligible bias as long as the number of missing items is up to 8 out of 25 items in each individual of the population.

Elevation of serum plasminogen activator inhibitor-1 predicts postoperative delirium independent of neural damage: a sequential analysis.

Older adult surgical patients are susceptible to developing delirium. Early intervention can be initiated if a potential biomarker associated with delirium can be identified during the acute phase of surgery. Therefore, we investigated the changes in the levels of serum inflammatory mediators responsible for delirium. Serum biomarkers were measured preoperatively to postoperative day 3 in 96 patients who underwent esophageal cancer surgery and compared between patients who did and did not develop delirium. Serum concentrations of the brain-derived phosphorylated neurofilament heavy subunit remained at higher levels throughout the entire perioperative period in patients with delirium (n = 15) than in those without delirium (n = 81). The interaction between delirium and non-delirium was significant for plasminogen activator inhibitor-1 (including age as a covariate, F = 13.360, p < 0.0001, η2 p = 0.134, observed power 1.000) during the perioperative periods. Plasminogen activator inhibitor-1 level discriminated between patients with and without clinically diagnosed delirium with significantly high accuracy (area under curve, 0.864; sensitivity, 1.00: negative predictive value, 1.000; p = 0.002). Rapid increases in the levels of serum plasminogen activator inhibitor-1 may enable clinicians to identify patients at risk of developing postoperative delirium and initiate early prevention and intervention.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Dynamic Postural Stability Is Decreased During the Single-Leg Drop Landing Task in Male Collegiate Soccer Players With Chronic Ankle Instability.

Background: Chronic ankle instability (CAI) is commonly encountered in soccer players. The feelings of instability and anxiety caused by CAI can lead to poor performance, such as difficulty in sharp change of direction during soccer play. The single-leg drop landing (SLDL) task is often used to evaluate dynamic postural stability. Purpose/Hypothesis: The purpose of this study was to clarify whether dynamic stability measured during SLDL is altered in male collegiate soccer players with CAI. The hypothesis was that athletes with CAI would show poor dynamic postural stability. Study Design: Controlled laboratory study. Methods: A total of 103 male collegiate soccer players were recruited, and their limbs were classified based on the new international CAI criteria. All players performed three 5-second SLDL trials on a force plate. The main outcome measures included time to stabilization of the horizontal ground-reaction force (GRF); peak GRF in the vertical, horizontal, and sagittal directions; and trajectory length of the center of pressure during SLDL. Results: Data from 59 CAI limbs and 147 non-CAI limbs were collected in this study. Time to stabilization of horizontal GRF was significantly longer in the CAI limbs (P < .001), and the peak GRFs in all directions were significantly lower in the CAI limbs (vertical, P < .001; horizontal, P < .001; sagittal, P = .001). Additionally, the trajectory length of the center of pressure was significantly greater in the CAI limbs (P = .004). Conclusion: Soccer players with CAI had decreased dynamic postural stability that led them to land softly when performing the SLDL task. Measurement of dynamic postural stability may be useful in the evaluation of CAI. Clinical Relevance: Our findings may be useful for strategies of daily training or as an evaluation tool.