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Background: We evaluated whether the Walkaide® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20–85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. Materials and Methods: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. Results: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: −8.26 to 29.98, p = 0.26), respectively. Conclusions: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604.

Pure motor isolated hand palsy (PMIHP) following infarction of the "hand knob" area is a rare entity in stroke. PMIHP usually recovers within the first few days, but there are rare cases where patients do not recover rapidly. Herein, we report a case of residual PMIHP in which repetitive facilitative exercise under concurrent low-amplitude continuous neuromuscular electrical stimulation ("RFE-under-cNMES") was introduced to improve hand function.A 65-year-old man with PMIHP (30 days after onset) participated in a rehabilitation program involving RFE-under-cNMES. This protocol followed an A1-B1-A2-B2 schedule, where the "A"-period consisted of RFE-under-cNMES ("A1," 2 weeks; "A2," 1 week), and the "B"-period consisted of 1-week conventional rehabilitation.The 5-week intervention promoted not only recovery from paralysis (8 points by the Fugl-Meyer Assessment), but also the ability to manipulate objects (13 points by the Action Research Arm test) and increased the subjective use of the affected upper limb during activities of daily living (2.88 points by the Motor Activity Log). Changes that exceeded the minimal clinically important difference occurred only in the RFE-under-cNMES period.The patient had improved outcomes. Further studies are required to determine the possibility of RFE-under-cNMES relieving motor paralysis in patients with PMIHP who do not recover rapidly.

Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated protein-1 (Plap-1) as a PDL-specific extracellular matrix protein. We generated knock-in mice expressing CreERT2 and GFP specifically in Plap-1-positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiate into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1−Ibsp+Sparcl1+ and Plap-1−Ibsp+Col11a2+, respectively. Other populations, such as Nes+ mural cells, S100B+ Schwann cells, and other non-stromal cells, were also identified. RNA velocity analysis suggested that a Plap-1highLy6a+ cell population was the source of PDLCs. Lineage tracing of Plap-1+ PDLCs during periodontal injury showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.

Genetic disturbance is propagated by artificial reinforcement or reintroduction of organisms from populations whose genetic structure is sufficiently different from the original populations. Many cultivars were produced from wild plant species, and fears exist that genetic disturbance of wild populations occurred by the human migration of cultivars. In this study, we detected genetic disturbance in Pecteilis radiata [= Habenaria radiata] (Orchidaceae) in the Hyogo Prefecture of Japan using multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq). Also, we estimated the risk of the spread of genetically disturbed individuals based on the results of spatial genetic structure and gene flow. In five out of 33 examined sites, we detected genetically disturbed individuals that possessed the same genetic cluster as cultivar samples. No spatial genetic structure was found among the sites within a 0.64 km radius, which indicated that pollen or seeds of P. radiata freely migrated among these populations. Consequently, we demonstrated that a risk exists of spreading genetic disturbances by gene flow within a radius of 0.64 km from the site where genetic disturbance was found. Raised public awareness of the risk of genetic disturbance would be necessary to prevent additional spread of genetic disturbances by human activities.

Understanding the degree of motor paralysis in stroke patients is important for assessing the severity of functional impairment and predicting functional prognosis. Fugl-MeyerAssessment for the lower extremities (FMA-LE)is a commonly used measure with high reliability and validity, but there is no official translated Japanese version of FMA-LE.This study aimed to develop Japanese FMA-LE and verify its reliability and validity in patients with acute stroke.The Japanese FMA-LE was developed following a standardized translation process. The reliability and validity were evaluated in 50 stroke patients at an acute care hospital. Validity was examined by determining the correlation between FMA-LEand Brunnstrom Recovery Stage (BRS), as well as Short Physical Performance Battery (SPPB). Intra-raterand inter-raterrelative reliabilities were evaluated by calculating intra-classcorrelation coefficients (ICCs). Absolute reliability was assessed by determining the standard error of the measurement and minimum detectible change (MDC). Systematic error was also assessed.FMA-LEtotal score was high correlated with BRS (ρ = 0.73,p .01) and moderately correlated with SPPB (ρ = 0.69,p .01). For intra-raterreliability, ICC was 0.98 (p .01), only fixed systematic error was observed (p .01), and MDC of the FMA-LEtotal score was 1.24. For inter-raterreliability, ICC was 0.98 (p .01), no systematic error was observed, and MDC of the FMA-LEtotal score was 3.23.The Japanese FMA-LE was reliable, valid, and useful for evaluating lower extremity function of acute stroke patients.

BACKGROUND: Gait analysis, such as portable gait rhythmogram (PGR), provides objective information that helps in the quantitative evaluation of human locomotion. OBJECTIVE: The purpose of this study was to assess the reliability of PGR in post-stroke patients. METHODS: Two raters (A and B) examined 48 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). RESULTS: There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93–0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97–0.98 (comfortable speed) and 0.97–0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25–1.49 (comfortable speed) and 1.62–1.77 (maximum speed) for intra-rater investigation, and 1.04–1.32 (comfortable speed) and 0.91–1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9–4.1%, and the error of an individual’s score at a given time point ranged from ±2.1–2.9%. CONCLUSIONS: Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

To provide a safe and appropriate out-of-bed program for stroke patients, screening for stroke-related functional impairments and disabilities should be performed in advance. However, few tools are available for clinical assessment of out-of-bed mobility while patients are still on bed. We sought to establish the validity and reliability of a newly developed Functional Bridge Test (FBT) for hemiplegic patients with acute stroke.This repeated-measures, observational study was conducted at a stroke care unit at an acute hospital. We assessed the validity of the FBT score, intra-rater and inter-rater reliabilities of the FBT, and concurrent validity of the FBT in stroke patients with hemiplegia. In addition to the original qualitative assessment, the FBT was also assessed quantitatively to evaluate the validity of the FBT score. Outcome measures included stroke severity, lower limb muscle strength, and basic mobility.We enrolled 32 patients with acute stroke. The newly developed FBT score had high validity. Intra-rater and inter-rater reliabilities (weighted kappa coefficient, 95% confidence interval) showed almost perfect agreement (0.95, 0.88-1.00; 0.98, 0.94-1.00, respectively). The FBT score was significantly associated with stroke severity, physical function, and basic mobility.The FBT has sufficient validity and reliability for acute stroke patients with hemiplegia. The advantages of the FBT in a clinical setting are based on its ability to be quickly administered on a bed without the need for specialized equipment. The FBT may help in screening functional impairment and disability in hemiplegic patients with acute stroke before they resume out-of-bed activities.

This study examined the immediate effects of neuromuscular electrical stimulation (NMES) on the dynamics of oropharyngeal structure and laryngeal vestibular closure (LVC) in healthy subjects.Ten healthy male volunteers participated in this controlled, before-and-after, videofluoroscopic swallowing pilot study. The study was conducted in four phases (each performed twice): (1) saliva swallow (SS) before evaluation (BEFORE), (2) NMES while at rest with no SS (NMES AT REST), (3) SS during NMES (DURING NMES), and (4) SS to examine the aftereffects of NMES (AFTER). We measured distances that oropharyngeal structures moved in the NMES AT REST phase, and we analyzed the kinematics of saliva swallowing primarily in the BEFORE and AFTER phases.Four changes in the morphology of the oropharyngeal structure caused by NMES AT REST were statistically significant: anterior-upward displacement of the hyoid bone and larynx, stretch of the laryngeal vestibule, and posterior ridge of the tongue root. Regarding the kinematics measured during SS, although there was no significant change in LVC reaction times, LVC duration in the AFTER phase was significantly longer than BEFORE. Regarding maximal displacement of the hyoid bone, there was significantly greater movement AFTER than BEFORE. As additional exploratory outcomes, the velocity of hyoid bone movement was significantly slower, and the hyoid-to-larynx approximation was significantly smaller, DURING NMES than AFTER.Longer duration of LVC might be caused by adaptive learning with NMES-induced structural changes in the oropharynx. Further clinical studies are warranted to determine whether this approach improves dysphagia, which impairs LVC.

To investigate the factors predicting oral feeding ability following acute stroke.This retrospective study compared patients admitted to a stroke care unit in 2 groups: an oral intake group and a tube feeding group. The groups were evaluated for 28 items and initial blood investigation tests, and the results compared. Logistic regression analysis was used to identify the clinical variables significantly associated with oral feeding ability.A total of 255 stroke patients (162 in the oral intake group and 93 in the tube feeding group) were admitted to the stroke care unit. Significant differences were observed between the 2 groups for 20 items. Logistic analysis found that the following variables were significant in the prediction model: age, date of initiation of oral feeding, stroke recurrence/patient deterioration during hospitalization, and date of initiation of occupational therapy.Factors associated with achieving oral intake among stroke care unit patients were: young age at time of admission; starting oral intake early; no stroke recurrence/patient deterioration during hospitalization; and achieving rehabilitation of daily activities early during the physical function recovery stage.

Background: A recent study revealed that whole-body vibration (WBV) tends to decrease spasticity in stroke-related hemiplegic legs. However, acute changes in cortical activation after WBV a...

Background and Aim In recent years, interest in the quality of medical care has rapidly increased worldwide. However, quality indicators that contribute to establishing standard treatment in stroke medicine, especially rehabilitation, are not well-developed in Japan. Japan has established Kaifukuki (convalescent) rehabilitation wards, and the development of quality indicators for stroke rehabilitation in the convalescent phase is an urgent issue. Methods We first reviewed the literature regarding quality indicators for stroke rehabilitation. Next, we extracted candidate indicators from identified reports and guidelines and surveyed educational hospitals certified by the Japanese Association of Rehabilitation Medicine. On the basis of the survey results, we reevaluated the suitability of the proposed indicators in discussions with an expert panel. Results The questionnaire survey highlighted several important items that revealed there is room for improvement in adherence. For stroke rehabilitation in the convalescent phase, we adopted 15 indicators that were feasible as indicators to be used for comparisons between facilities, based on scoring by and opinions of the expert panel. These indicators measured structure (2 indicators), process (5 indicators), and outcome (8 indicators). Conclusion This is the first study to establish quality indicators to standardize stroke rehabilitation in Japan. We developed this set of 15 indicators using an evidence-based approach. However, many tasks remain for continuous quality improvement.

An X-band transverse-deflecting structure is a crucial RF unit for bunch-length measurement conducted at the Shanghai Soft-X-ray Free Electron Laser Facility (SXFEL) at the Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences. The target of this prototype deflector is to operate at 30 MW to have a deflection of 10 MV/structure to realize 20-fs resolution in a full-size structure (0.6 meters long, used on user facility of SXFEL), which satisfies the requirement of the linac beam size measurement at 840 MeV. The program was started in 2010 focusing on X-band deflectors, including design, fabrication, and RF measurement. The electrical tuning of the deflector was successfully done using a unique “cage”-type bead. Recently, a high-power test was conducted at KEK on the first prototype deflector. The high-gradient features at the nominal gradient was proven, but the further increase of power and pulse width was limited at 45 MW with a 173-ns pulse width due to approaching the feasible limit of the modified pointing vector value 5 MW/mm2. In this final stage, frequent breakdowns near the badly brazed point occurred and further conditioning had to be suspended owing to limited available time.

Localized surface plasmon resonance (LSPR) in a silver (Ag) nanosphere dimer embedded in silicate glass was investigated using scanning transmission electron microscopy electron energy-loss spectro...

Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study. We first devised a new protocol to isolate PDL cells from the surface of adult murine molars and established 35 new single cell-derived clones from the PDL explant. Among these clones, six clones with high (high clones, n = 3) and low (low clones, n = 3) osteogenic potential were selected. Despite a clear difference in the osteogenic potential of these clones, no significant differences in their cell morphology, progenitor cell marker expression, alkaline phosphatase activity, proliferation rate, and differentiation-related gene and protein expression were observed. RNA-seq analysis of these clones revealed that Z-DNA binding protein-1 (Zbp1) was significantly expressed in the high osteogenic clones, indicating that Zbp1 could be a possible marker and regulator of the osteogenic differentiation of PDL progenitor cells. Zbp1-positive cells were distributed sparsely throughout the PDL. In vitro Zbp1 expression in the PDL clones remained at a high level during osteogenic differentiation. The CRISPR/Cas9 mediated Zbp1 knockout in the high clones resulted in a delay in cell differentiation. On the other hand, Zbp1 overexpression in the low clones promoted cell differentiation. These findings suggested that Zbp1 marked the PDL progenitors with high osteogenic potential and promoted their osteogenic differentiation. Clarifying the mechanism of differentiation of PDL cells by Zbp1 and other factors in future studies will facilitate a better understanding of periodontal tissue homeostasis and repair, possibly leading to the development of novel therapeutic measures.

Background and aims: In patients with severe hypertension, or history of stroke, the lower limit of cerebral blood flow (CBF) autoregulation is shifted to a higher blood pressure (BP) than in healthy subjects. The aim of this study was to compare the effects of olmesartan/azelnidipine combination (OLM/AZ) vs high-dose of olmesartan on ambulatory blood pressure (ABPM), cognitive function, and rehabilitation outcome in the post-stroke patients with hypertension. Methods: A total of 36 patients, 20 men and 16 women, aged 58-72 years, with sitting diastolic BP >90mmHg and systolic BP >140mmHg were eligible for participation in the present study. We randomly assigned 36 patients to either the OLM/AZ group or high-dose olmesartan group for 12 weeks. At the end of a 2-week wash-out period and after 12 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed, and cognitive function was evaluated through neuropsychological testing. In addition, rehabilitation outcome measurements were also collected during study period. Results: Both treatments significantly reduced ambulatory BP. However, the OLM/AZ produced a greater reduction in 24-h, day-time and night time ABPM values. High-dose olmesartan did not induce significant changes in any of the cognitive function test scores, whereas at 12 weeks OLM/AZ significantly improved the neuropsychological test score (Digid span test, Token test, Digital symbol test, Trail making test part A and B) (p< 0.01). Patients treated with OLM/AZ showed effective rates of improvement in hand (38.9%), upper extremities (55.6%) and lower extremities (72.2%), measured by Brunnstrom stage; these improvements were significantly different from those in high-dose olmesartan group for the total (P< 0.05) scores. Conclusions: These results suggest that in hypertensive post-stroke patients treatment with OLM/AZ produces a slightly greater reduction in ambulatory BP than high-dose olmesartan, and unlike this latter, improves some of the components of cognitive function, particularly psychomotor speed, attention and mentation. Our results suggest that OLM/AZ may improve cognitive function and rehabilitation outcome in hypertensive stroke patients in whom CBF autoregulation is impaired.

Background and Aims: The functional electrical stimulation (FES) is the electrical stimulation of a muscle deprived of nervous control for providing muscular contraction and thereby producing a functionally useful movement. FES is particularly effective for treating foot drop caused by stroke. The purpose of this study was to investigate the effect of WalkAide FES system on functional recovery and activities of daily living (ADL) in stroke patients with foot drop. Methods: Participants (n=203; 49 females and 154 males; time after stroke 61.6±31.5 days) were randomized to either FES group or the control group. All subjects participated in the same standard rehabilitation program. In addition, FES group participated in FES training for 40 mins per day, five times a week, for 8 weeks, and those in the control group participated in the usual physical therapy including gait re-education, gait training with an orthotic device, and muscle stretching. Functional recovery was assessed using 6-min walk test (6MWT), active range of motion of ankle dorsiflexion (A-ROM), and Timed Up and Go test (TUG). ADL was assessed using 10-m walk test (10MWT), Stroke Impact Scale (SIS), and patient satisfaction. Results: After intervention, there were significant improvements in 6MWT, TUG, 10MWT, SIS compared to baseline in both groups (p< 0.0001). The significant improvement in A-ROM was demonstrated only in FES group. At follow-up, AROM showed significant improvements in the FES group compared to the control group (p= 0.0011). However, when comparing average change scores from baseline to end of treatment, significant differences were noted only for the A-ROM scores. Stroke patients preferred the use of an electrical stimulation orthotic substitute device to an orthotic device, according to the questionnaire of patient satisfaction (p< 0.0001). Conclusions: The findings of the current study demonstrated the efficacy of FES on the functional recovery and ADL, and also showed the feasibility of applying FES for dropped foot during the convalescent phase of recovery after stroke. These results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings.

Balneotherapy is a treatment with healing waters, which includes bathing and physiotherapy in thermal water, therapeutic drinks, medical massage, and water jet massage. It is based on the buoyancy, physical properties, temperature, and chemical effects of mineral water. Throughout European and Japanese medical institutions, balneology and hot spring therapy is very much a part of routine medical treatment. The mechanism of balneotherapy is not yet completely understood. Balneotherapeutic procedures are mainly performed for the prevention, treatment, and rehabilitation of musculoskeletal diseases, but they have also proven useful for various other indications such as for the treatment or rehabilitation of dermatological diseases, immuno-inflammatory diseases, chronic pain syndromes, chronic cardiac diseases, and metabolic syndromes or neurological diseases as well as in the rehabilitation of patients with psychiatric conditions. Balneotherapy works well in the case of muscle tension, as it is relieving and relaxing, and it may be associated with improvement of various diseases. However, further investigations are necessary to determine the effectiveness, safety, standard procedures, and potential side effects of balneotherapy.

In this paper, the development of an accelerating structure with high-purity copper operated at approximately 20 K is described. The aim is to obtain a dramatic increase in the quality factor (Q factor), which is an important parameter as regards enhancement of the acceleration gradient in a normal-conducting accelerating structure that has been operated at room temperature in the past. First, the Q factors of pillbox cavities comprised of two types of copper with different purities (99.99% and 99.99998%) were measured, at room temperature (300 K) and at a relatively low temperature (20 K); the resultant ratios, Q 0(20 K)/Q 0(300 K), were then compared with calculated values. Hence, it was found that the experimental and calculated values agree to within several percent, and converge to a constant value (approximately 5.3) when the residual resistance ratio is above 500. Next, a C-band accelerating structure was fabricated using a copper material having a purity of 99.99998%, and high-power testing of the structure was conducted at 20 K. Hence, it was found that the accelerating gradient E acc reaches 30.9 MV/m with a 1.0- μ s pulse width and 50-Hz repetition rate. In the high-power test, it was revealed that the radiation dose rate for C-band structure (20 K) was about two orders of magnitude lower than that for S-band structure (303 K) under the same conditions. Further, the magnitude of the dark current generated in this structure was estimated to be several femtoamps, which was below the detection limit. This finding was based on the assumption that the dark current magnitude is proportional to the radiation dose; however, no dark current was observed.

[Purpose] This study investigated the short-term effects of a combination therapy consisting of repetitive facilitative exercises and orthotic treatment. [Subjects and Methods] The subjects were chronic post-stroke patients (n=27; 24 males and 3 females; 59.3 ± 12.4 years old; duration after onset: 35.7 ± 28.9 months) with limited mobility and motor function. Each subject received combination therapy consisting of repetitive facilitative exercises for the hemiplegic lower limb and gait training with an ankle-foot orthosis for 4 weeks. The Fugl-Meyer assessment of the lower extremity, the Stroke Impairment Assessment Set as a measure of motor performance, the Timed Up & Go test, and the 10-m walk test as a measure of functional ambulation were evaluated before and after the combination therapy intervention. [Results] The findings of the Fugl-Meyer assessment, Stroke Impairment Assessment Set, Timed Up & Go test, and 10-m walk test significantly improved after the intervention. Moreover, the results of the 10-m walk test at a fast speed reached the minimal detectible change threshold (0.13 m/s). [Conclusion] Short-term physiotherapy combining repetitive facilitative exercises and orthotic treatment may be more effective than the conventional neurofacilitation therapy, to improve the lower-limb motor performance and functional ambulation of chronic post-stroke patients.

[Purpose] Gait analysis, such as portable gait rhythmogram (PGR) provides objective information that helps in the quantitative evaluation of human locomotion. The purpose of this study was to assess the reliability of PGR in post-stroke patients. [Subjects and Methods] Two raters (A and B) examined 44 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). [Results] There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93-0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97-0.98 (comfortable speed) and 0.87-0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25-1.49 (comfortable speed) and 1.62-1.77 (maximum speed) for intra-rater investigation, and 1.04-1.32 (comfortable speed) and 0.91-1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9-4.1%, and the error of an individual's score at a given time point ranged from ±2.1-2.9%. [Conclusion] Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

IntroductionIncreasing evidence supports the utilisation of functional electrical stimulation (FES) to improve gait following stroke; however, few studies have focused exclusively on its use in the convalescent phase. In addition, its efficacy in patients with a non-Western life style has not been evaluated.Methods and analysisThis is a randomised, controlled, open-label multicentre study, comparing rehabilitation with and without FES. The purpose of our study is to test the hypothesis that the FES system improves walking ability in Japanese patients with hemiplegia during the convalescent phase. Two hundred patients aged 20–85 years who had an initial stroke ≤6 months prior to the enrolment, are in a convalescent phase (after the end of acute phase treatment, within 6 months after the onset of stroke) with functional ambulation classification 3 or 4 and have a hemiplegic gait disorder (drop foot) due to stroke have been recruited from 21 institutions in Japan. The patients are randomised in 1:1 fashion to usual gait rehabilitation or rehabilitation using FES (Walkaide). The trial duration is 8 weeks, and the primary outcome measured will be the change in maximum distance from baseline to the end of the trial, as measured with the 6 min walk test (6-MWT). The 6-MWT is performed barefoot, and the two treatment groups are compared using the analysis of covariance.Ethics and disseminationThis study is conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects and is approved by the ethics committee of all participating institutions. The published results will be disseminated to all the participants by the study physicians.Trial registration numberThe University Hospital Medical Information Network-Clinical Studies Registry (UMIN000020604).

Lysosome transports mineralizing nanovesicle in osteoblasts., Mineralization is the most fundamental process in vertebrates. It is predominantly mediated by osteoblasts, which secrete mineral precursors, most likely through matrix vesicles (MVs). These vesicular structures are calcium and phosphate rich and contain organic material such as acidic proteins. However, it remains largely unknown how intracellular MVs are transported and secreted. Here, we use scanning electron-assisted dielectric microscopy and super-resolution microscopy for assessing live osteoblasts in mineralizing conditions at a nanolevel resolution. We found that the calcium-containing vesicles were multivesicular bodies containing MVs. They were transported via lysosome and secreted by exocytosis. Thus, we present proof that the lysosome transports amorphous calcium phosphate within mineralizing osteoblasts.

To investigate whether a footbath inhibits spasticity in the hemiplegic lower limbs of post-stroke patients.Randomized, controlled study.Rehabilitation education and research hospital.Twenty-two post-stroke patients were randomly allocated to control or experimental groups. After relaxing in a supine posture for 30min, the experimental group subject's legs were immersed in 41°C water below the knee joint for 15min, while the control group remained in a resting posture.Modified Ashworth Scale (MAS) scores of the affected triceps surae muscle and F-wave parameters (i.e., F-wave amplitude, F/M ratio, and F-wave persistence) were recorded before, immediately after, and 30min after each intervention. Physiological parameters were simultaneously monitored to determine the thermo-therapeutic mechanisms and side effects of footbath usage.At the time immediately after the intervention, F-wave amplitudes decreased significantly in the experimental group, compared to the control group (p0.01, difference: -106.8; 95% CI; -181.58 to -32.09). F-wave amplitudes decreased significantly after 30-min intervention in the experimental group, with a total reduction of 161.2μV being recorded compared to 8.8μV increase in the control group (p0.01, difference: -170.0; 95% CI; -252.73 to -87.33). There were also significant differences between the experimental and control group for both F/M ratio and F-wave persistence, immediately after and 30min after the intervention. Further, there were significant differences between the experimental and control group for the MAS scores immediately after the intervention (p0.05, difference: -0.72; 95% CI; -1.262 to -0.193), and 30min after the intervention (p0.05, difference: -0.73; 95% CI; -1.162 to -0.293).These findings demonstrate that the use of footbaths is an effective non-pharmacological anti-spastic treatment for use in stroke rehabilitation.

Functional electrical stimulation (FES) for patients with stroke and foot drop is an alternative to ankle foot orthoses. Characteristics of FES responders and nonresponders have not been clarified.(1) To investigate the effects of treatment with FES on patients with stroke and foot drop and (2) to determine which factors may relate to responders and nonresponders.Multicenter, nonrandomized, prospective study.Multicenter clinical trial.Participants included those who experienced foot drop resulting from stroke, were older than 20 years, and could provide consent to participate; they were enrolled from hospitals between January 2013 and September 2015 and performed rehabilitation with FES.Stroke Impairment Assessment Set Foot-Pat Test (SIAS-FP), Fugl-Meyer Assessment for Lower Extremity (FMA-LE), Modified Ashworth scale (MAS) for ankle joint dorsiflexion and plantar flexion muscles, range of motion (ROM) for ankle joint, 10-m walking test (10mWT), Timed UpGo test (TUG), and 6-minute walking test (6MWT) were evaluated pre- and postintervention. Age, gender, type of stroke, onset times of stroke, paretic side, Brunnstrom stage of the lower extremity (Br. stage-LE), Functional Independence Measure (FIM), Functional Ambulation Category (FAC), poststroke months, number of interventions, total hours of interventions, and whether a brace was used were extracted from patients' medical records and collected on the physiological examination day.The authors examined 10mWT and age, gender, type of stroke, onset times of stroke, paretic side, Br. stage-LE, FIM, FAC, poststroke months, number of interventions, total hours of interventions, whether a brace was used, SIAS-FP, FMA-LE, MAS, ROM, TUG, and 6MWT before intervention. Participants were divided into nonresponders and responders with a change in 10mWT of0.1 and ≥0.1 m/s, respectively. Single and multiple regression analyses were used for data analysis. Additionally, the changes between groups were compared.Fifty-eight responders and 43 nonresponders were enrolled. The between-group differences, compared for changes between pre- and postintervention, were significant in terms of changes in SIAS-FP (P = .02), 10mWT (P.001), 10-m gait steps (P .001), TUG (P = .04), and 6MWT (P = .006). In the adjusted regression model, gender (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.426-12.25; P = .007), number of interventions (OR, 1.028; 95% CI, 1.003-1.070; P = .03), and active ankle joint dorsiflexion ROM (OR, 1.047; 95% CI, 1.014-1.088; P = .005) remained significant.The factors related to 10mWT showing changes beyond the minimal clinically important difference were found to be patient gender, number of interventions, and active ankle joint dorsiflexion ROM before intervention. When patients with stroke who have greater active ankle joint ROM, and are female, use FES positively, they may benefit more from using FES.II.

A Compact Linear Collider prototype traveling-wave accelerator structure fabricated at Tsinghua University was recently high-gradient tested at the High Energy Accelerator Research Organization (KEK). This $X$-band structure showed good high-gradient performance of up to $100\text{ }\text{ }\mathrm{MV}/\mathrm{m}$ and obtained a breakdown rate of $1.27\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}8}$ per pulse per meter at a pulse length of 250 ns. This performance was similar to that of previous structures tested at KEK and the test facility at the European Organization for Nuclear Research (CERN), thereby validating the assembly and bonding of the fabricated structure. Phenomena related to vacuum breakdown were investigated and are discussed in the present study. Evaluation of the breakdown timing revealed a special type of breakdown occurring in the immediately succeeding pulse after a usual breakdown. These breakdowns tended to occur at the beginning of the rf pulse, whereas usual breakdowns were uniformly distributed in the rf pulse. The high-gradient test was conducted under the international collaboration research program among Tsinghua University, CERN, and KEK.

We report herein a 70-year-old woman, with repeated thromboembolic events, including three cerebral embolisms and two venous thromboembolisms, despite adequate anticoagulant therapy. Trousseau syndrome was suspected, and she was diagnosed as having lung adenocarcinoma. Chemoradiotherapy was started, achieving improvements in the lung cancer, and thrombosis was also brought under control. Ten months later, the lung cancer relapsed, and second-line chemotherapy was performed. D-dimer levels, which had normalized after the first-line therapy, increased together with the relapse, but became negative again following the chemotherapy. In general, the prognosis of Trousseau syndrome is diverse. However, in this case, the course was good following the second lung cancer therapy: D-dimer levels did not increase, and there were no recurrences of thromboembolism. This experience reminds us the prognosis is most affected by whether the underlying disease is being effectively treated, and suggests that for Trousseau syndrome, despite adequate anticoagulant therapy, elevation of D-dimer levels should consider the recurrent cancer.