FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

[The effect of rehabilitation and one year follow-up for a COVID-19 patient on prolonged mechanical ventilation].

We herein report the outcomes of rehabilitation intervention for a patient in his 80s with chronic obstructive pulmonary disease on prolonged mechanical ventilation after COVID-19 infection. The patient was forced to be long-term bedridden due to respirator dependence, showing notable muscle weakness and needing full assistance for all of his activities of daily living (ADL). We implemented rehabilitation for the purposes of withdrawal from mechanical ventilation and improvement of his physical function. We provided a combination program of range of motion exercise, resistance training, and gradual mobilization, such as sitting on the edge of the bed, moving between the bed and wheelchair, sitting on the wheelchair, standing and walking. After rehabilitation for 24 days, the patient was withdrawn from mechanical ventilation, his muscle strength recovered to a level of 4 (Good) on manual muscle testing (MMT) and he became able to walk using a walker. A follow-up survey one year later confirmed that he performed ADL without assistance and returned to work.

Evaluation of motor learning in predictable loading task using a force sense presentation device.

Neural circuits connecting the cerebellum with the cerebral cortex are important for both motor and cognitive functions. Therefore, assessment of cerebellar function is clinically important for patients with various motor and cognitive dysfunctions. Cerebellum-dependent motor learning has been studied using various tasks. The most widely used tasks are visuomotor adaptation tasks, in which subjects are required to make movements in two dimensions. Studies using simpler tasks of one-dimensional movement, which are easier for patients with motor problems to perform, have suggested that anticipatory responses in these tasks are useful to evaluate cerebellum-dependent motor control or motor learning. In this study, we examined whether the motor learning process can be evaluated in a simple loading task. Using space interface device for artificial reality (SPIDAR), a constant downward force was loaded to subjects' hands in a predictable condition, and the vertical movement of the hand was recorded. The hand deflection from the initial position was displayed on a screen for visual feedback information. We examined effects of repeated loading task training (90 times) on hand movements, by analyzing a small upward movement just before loading (anticipatory response) and a large downward movement after loading in each trial. We found that the repeated training lowered the time constant of upward movement and reduced the amplitude and time-to-peak of downward movement. These training effects were maintained into the next day. Furthermore, we found that loading task training with eyes closed was also effective, which indicates that proprioceptive information is enough for improvement of performance.

A novel telerehabilitation with an educational program for caregivers using telelecture is feasible for fall prevention in elderly people: A case series.

BACKGROUND: The importance of fall prevention rehabilitations has been well recognized. Recently telerehabilitation was developed, however, there have been no reports on telerehabilitation with direct support from specialists for fall prevention among the elderly. We herein reported telerehabilitation by caregivers educated by our novel educational program. METHODS: Caregivers were educated with our educational program using a telelecture system and supported telerehabilitation following instructions from rehabilitation specialists in our university using the telemedicine system every two to four weeks for three months. Caregivers were assessed with our original questionnaire before and after the telelecture. Participants were assessed by the Berg Balance Scale (BBS), Timed Up & Go test (TUG test), Hand-held dynamometer (HHD) and Mini-Mental State Examination (MMSE) before and after telerehabilitation. Wilcoxon's signed-rank test was used for the statistical analyses. A value of P<.05 was considered statistically significant. RESULTS: Nine elderly people were enrolled. The mean age was 84.7 (78-90) years old and the sex ratio was 1:8 (males:females). The average number of telerehabilitation sessions was 4.7. The average score of nineteen caregivers before the lecture was 15.3, while that after the lecture was 18.3. Caregivers' understanding was significantly increased after the telelecture (P<.001). No adverse events occurred during the study period. The median values of the BBSs, TUG test, right and left HHD and MMSE before and after 3 months' telerehabilitation were 43 (95% confidence interval [CI]: 40.10, 49.01) and 49 (95% CI: 41.75, 50.91), 17.89 (95% CI: 15.51, 23.66) and 18.53 (95% CI: 14.56, 25.67), 7.95 (95% CI: 4.38, 10.14) and 11.55 (95% CI: 7.06, 13.55), 9.85 (95% CI: 6.79, 12.59) and 13.20 (95% CI: 7.96, 14.42), and 19 (95% CI: 12.34, 21.66) and 16 (95% CI: 10.81, 21.00), respectively. Although approximately half of the participants showed improvement in the BBS, TUG test, right and left HHD and MMSE, no significant changes were observed (P=.7239, P=.3446, P=.1023, P=.3538 and P=.8253, respectively). CONCLUSIONS: Our telerehabilitation program exhibited significant effects in elderly people and improved the degree of understanding concerning rehabilitation among caregivers in facilities for elderly people.

Portable rehabilitation system with brain-computer interface for inpatients with acute and subacute stroke: A feasibility study.

The feasibility and safety of brain-computer interface (BCI) systems for patients with acute/subacute stroke have not been established. The aim of this study was to firstly demonstrate the feasibility and safety of a bedside BCI system for inpatients with acute/subacute stroke in a small cohort of inpatients. Four inpatients with early-phase hemiplegic stroke (7-24 days from stroke onset) participated in this study. The portable BCI system showed real-time feedback of sensorimotor rhythms extracted from scalp electroencephalograms (EEGs). Patients attempted to extend the wrist on their affected side, and neuromuscular electrical stimulation was applied only when the system detected significant movement intention-related changes in EEG. Between 120 and 200 training trials per patient were successfully and safely conducted at the bedside over 2-4 days. Our results clearly indicate that the proposed bedside BCI system is feasible and safe. Larger clinical studies are needed to determine the clinical efficacy of the system and its effect size in the population of patients with acute/subacute post-stroke hemiplegia.

Relationship between chopstick manipulation and cross-sectional shape in the developmental stages from infancy to early school age.

Motor development was investigated in 114 children aged 4-9 years, and the effects of different cross-sectional shapes of chopsticks (octagonal, square, and triangular) on manipulation ability were examined. Children's chopstick manipulation was found to be related to the developmental stage and their way of holding them. Manipulation was enhanced when they transmitted the optimal force to the tips when closing, the bottom chopstick was stabilized when opening, and the upper chopstick was encouraged to rotate moderately. In addition, opening chopsticks is more difficult than closing them. Square chopsticks increase the force of the tips, whereas octagonal chopsticks encourage more rotation of the upper chopstick, indicating that differences in the ability to manipulate chopsticks during development affect the preference for cross-sectional shapes. We plan to examine the effectiveness of chopsticks with different cross-sectional shapes of the upper and bottom chopsticks by focusing on the opening operation.

Impact of blood pressure on the outcomes of inpatients with Subarachnoid hemorrhage: A retrospective cross-sectional study.

ABSTRACT: It is unclear whether antihypertensive treatment should be indicated after subarachnoid hemorrhage (SAH). Hence, we investigated the impact of blood pressure on inpatient outcomes after SAH rehabilitation.This retrospective cross-sectional study analyzed data of SAH inpatients, as obtained from the Japan Association of Rehabilitation Database for inpatients undergoing SAH rehabilitation. Inpatients admitted to a conventional ward with a diagnosis of cerebrovascular disease were voluntarily registered in this database between January 2006 and December 2013 from hospitals in Japan. Patients were categorized into hypertensive and non-hypertensive populations and assessed using the Barthel Index (BI) and the total BI score at hospital discharge. We compared the independent population (patients with the highest score for each activity) with its non-independent counterpart. Data on the patients' age, BI score on admission, total BI score, BI score increase, daily BI score increase, hospitalization duration, BI activities, patients' sex, and Brunnstrom recovery stage were compared.Eighty-eight patients with SAH were analyzed; 43 were hypertensive and 45 non-hypertensive. Hypertension was associated with increased non-independence levels (hypertensive versus non-hypertensive patients, transfers [bed to chair and back]: 15 versus 24, P = .03, odds ratio (OR) = 2.532 (95% confidence interval [CI], 1.065-6.024); toilet use: 15 versus 24, P = .03, OR = 2.532 (95% CI, 1.065-6.024); bathing: 23 versus 34, P = .0061, OR = 3.623 (95% CI, 1.414-9.259); stair climbing: 22 versus 31, P = .03, OR = 2.703 (95% CI, 1.114-6.579); and bladder control: 14 versus 24, P = .02, OR = 2.801 (95% CI, 1.170-6.711)). The total BI score of the hypertensive inpatients at discharge was lower than that of their non-hypertensive counterparts (0-75 versus 80-100, 30 versus 19, P = .03). Moreover, the BI score increase per day was significantly lower in the hypertensive group than in the non-hypertensive group (.67 versus 1.8, P = .02). The hypertensive group also had a significantly longer duration of hospitalization than the hypertensive group (52 versus 30 days, P = .02).Hypertension was associated with longer hospitalization and poorer outcomes post-discharge, suggesting the importance of strict blood pressure control in patients who have experienced SAH.

A Case of Chronic Limb-Threatening Ischemia with Heel Ulcers Cured by Revascularization and Partial Calcanectomy.

Ischemic limbs with infected heel ulcers are often difficult to salvage. We present a case of an 82-year-old woman who had bilateral heel ulcers owing to chronic limb-threatening ischemia. She underwent right femoral-terminal posterior tibial artery bypass surgery, but right calcaneus osteomyelitis occurred and inhibited wound healing. She underwent partial calcanectomy (PC), and her right heel healed six months after the bypass surgery. The ulcer on her left foot also healed after distal bypass and PC. We describe our experience with a patient who needed PC to cure her heel ulcers.

Spasticity and Range of Motion Over Time in Stroke Patients Who Received Multiple-Dose Botulinum Toxin Therapy.

OBJECTIVE: This study examined how the effects of botulinum toxin therapy changed over time by sequential evaluation of clinical improvements in spasticity and contracture in 24 chronic-stage stroke patients on repeated botulinum toxin therapy who were receiving fewer rehabilitation interventions. METHODS: Botulinum toxin injection was administered into the spastic muscle of the paralyzed upper or lower limb 5 times with at least 3-month intervals. Modified Ashworth Scale and range of motion were measured before and 2 weeks after each dose in the extremities to compare the first measurement value with subsequent values. Each predose value was also compared with the first predose value. RESULTS: Compared with predose scores, Modified Ashworth Scale significantly improved in all flexors after 2 weeks from the first to fifth doses. Range of motion significantly improved in wrist dorsiflexion and ankle dorsiflexion. Comparison of values before each dose versus the first predose value showed significant improvement both in the Modified Ashworth Scale score of wrist flexors, finger flexors, and ankle planter flexors, and the range of motion of elbow extension, wrist dorsiflexion, and ankle dorsiflexion. CONCLUSION: The comparison of predose values versus 2-week postdose values indicated that the effect of botulinum toxin formulation would not lessen after repeated injections with continuous improvements of Modified Ashworth Scale and range of motion. The comparison of predose values versus the first predose value also suggested that multiple injections of botulinum toxin formulation could be more effective in reducing spasticity and increasing the range of motion than a single injection.

Successful limb salvage through staged bypass combined with free gracilis muscle transfer for critical limb ischemia with osteomyelitis after failed endovascular therapy.

BACKGROUND: Critical limb ischemia with osteomyelitis is so difficult to treat that even appropriate revascularization and wound therapy cannot achieve limb salvage because of uncontrollable infection. It is still difficult to judge the possibility of limb salvage before revascularization. CASE PRESENTATION: A 73-year-old male complained of a small ulcer on his left toe, which was treated with multiple endovascular therapy. After failed endovascular therapy, he suffered extensive tissue loss with tibial osteomyelitis. We carried out staged surgery that was composed of dual bypass to the sural artery and posterior tibial artery. After intensive debridement and wound care, insertion of a subsequent free gracilis muscle flap to cover the exposed tibial bone was performed, achieving functional limb salvage. CONCLUSION: Even in the threatened limb with extensive tissue loss and osteomyelitis, intensive and multidisciplinary treatment with staged revascularization, muscle transfer, and appropriate wound care achieved functional limb salvage.

A Significant Association of Malnutrition with Dysphagia in Acute Patients.

Dysphagia and malnutrition seem to be associated, but little research in detail has been reported. We aimed to clarify the association between dysphagia and malnutrition by adopting accurate diagnosis and mathematical evaluation of dysphagia using videofluorography and nutritional assessment calculated by a well-established nutritional risk index. We conducted a retrospective analysis of 165 enrolled patients who were admitted to our hospital for acute diseases and underwent videofluorography on suspicion of dysphagia in the year 2016. We diagnosed high-risk dysphagia in patients with 8-point penetration-aspiration scale (PAS) score over 4. We used the geriatric nutritional risk index (GNRI) as a nutritional assessment tool. A GNRI score less than 91.2 corresponds to malnutrition. The median age of 165 enrolled patients was 76.0, and the number of female patients was 53. The mean GNRI was 81.2, and 134 patients (81.2%) had malnutrition. The number of the patients with a diagnosis of high-risk dysphagia was 54 (32.7%). The GNRI of patients with high-risk dysphagia was significantly less than that of patients without (mean value 77.7 ± 10.5 vs. 83.0 ± 10.5, P = 0.003). GNRI < 91.2 was independently and significantly associated with high-risk dysphagia (OR 3.094; CI 1.057-9.058; P = 0.039). Based on the current study, the authors propose evaluating nutritional status to predict dysphagia risk of patients in the acute phase.

Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction.

Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition.

Relief of neuropathic pain after spinal cord injury by brain-computer interface training.

OBJECTIVES: The aim of this study was to report the effects of brain-computer interface (BCI) training, a neurofeedback rehabilitation technique, on persistent neuropathic pain (NP) after cervical spinal cord injury (SCI). SUBJECTS AND METHODS: We present the case of a 71-year-old woman with NP in her left upper extremity after SCI (C8). She underwent BCI training as outpatient rehabilitation for 4 months to enhance event-related desynchronization (ERD), which is triggered by the patient's motor intuition. Scalp electroencephalography was recorded to observe the ERD during every BCI training session. The patient's pain was evaluated with the McGill Pain Questionnaire (MPQ) and a visual analog scale (VAS). The MPQ was performed after every BCI training session, and the patient assessed the VAS score on her own, once every few days during the BCI training period. RESULTS: After the BCI training started, the patient's ERD during the BCI training period increased significantly, from 15.6-30.3%. Moreover, her VAS score decreased gradually, from 8 to 5, after the BCI training started, although the MPQ did not change significantly. CONCLUSION: BCI training has the potential to provide relief for patients with persistent NP via brain plasticity, and to improve their activities of daily living and quality of life.

[A Case of Liver and Pulmonary Metastases from Adamantinoma, a Bone Tumor].

This case involved a 28-year-old man who had undergone surgery and perioperative chemotherapy for an adamantinoma of the right tibia with multiple lung metastases. Sixteen months after the initial diagnosis, CT revealed an 8 cm diameter liver metastasis and right pneumothorax with little change in the lung metastases. Liver resection and partial pneumonectomy were performed. Pathologic findings confirmed that both liver and lung specimens had metastases from the adamantinoma. Dissimilar from the primary lesion with much interstitial tissue and spindle-shaped cells, the liver metastasis had very dense cell proliferation without interstitial tissue and dominant epithelial parts, suggesting a higher malignant potential. If other lesions are under good control, resection of the newly appearing metastasis, which has a higher malignant potential, might improve prognosis. Further accumulation of cases and detailed studies is required.

Multimodal sensory feedback associated with motor attempts alters BOLD responses to paralyzed hand movement in chronic stroke patients.

Electroencephalogram-based brain-computer interfaces (BCI) have been used as a potential tool for training volitional regulation of corticomuscular drive in patients who have severe hemiplegia due to stroke. However, it is unclear whether ERD observed while attempting motor execution can be regarded as a neural marker that represents M1 excitability in survivors of severe stroke. Therefore we investigated the association between ERD and the blood-oxygen-level-dependent (BOLD) fMRI signal during attempted movement of a paralyzed finger in stroke patients. Nine chronic stroke patients received BCI training for finger extension movement 1 h daily for a duration of 1 month. The sensorimotor rhythm was recorded from the sensorimotor area of the damaged hemisphere, and ongoing amplitude variations were monitored using a BCI system. Either a visual alert or the action of a motor-driven orthosis was triggered in response to ERD of the sensorimotor rhythm while patients attempted extension movements of the paralyzed fingers. Inter-subject covariance between ERD and the BOLD response in the sensorimotor areas was calculated. After BCI training, an increased ERD over the damaged hemisphere was confirmed in all participants while they attempted extension of the affected finger and this increase was associated with a BOLD response in primary sensorimotor area. Whole-brain MRI revealed that the primary sensorimotor area and supplementary motor area were activated in the damaged hemisphere after 1 month of BCI training. ERD reflects the BOLD responses of the primary motor areas in either hemisphere while patients who have severe chronic hemiplegia due to a stroke attempt an extension movement of the paralyzed fingers. One month of BCI can alter motor-related brain area activation. Combining BCI with other methods to facilitate such changes may help to implement BCI for motor rehabilitation after stroke.

Functional recovery from chronic writer's cramp by brain-computer interface rehabilitation: a case report.

BACKGROUND: Dystonia is often currently treated with botulinum toxin injections to spastic muscles, or deep brain stimulation to the basal ganglia. In addition to these pharmacological or neurosurgical measures, a new noninvasive treatment concept, functional modulation using a brain-computer interface, was tested for feasibility. We recorded electroencephalograms (EEGs) over the bilateral sensorimotor cortex from a patient suffering from chronic writer's cramp. The patient was asked to suppress an exaggerated beta frequency component in the EEG during hand extension. RESULTS: The patient completed biweekly one-hour training for 5 months without any adverse effects. Significant decrease of the beta frequency component during handwriting was confirmed, and was associated with clear functional improvement. CONCLUSION: The current pilot study suggests that a brain-computer Interface can give explicit feedback of ongoing cortical excitability to patients with dystonia and allow them to suppress exaggerated neural activity, resulting in functional recovery.

[Selection of treatment modalities in patients with spasticity].

Spasticity is the most common abnormality of muscle tone. Typically, oral antispastic drugs, phenol blocks, motor-point blocks, selective dorsal rhizotomies, and selective peripheral neurotomies are used to reduce muscle tone and/or improve ranges of motion. Recently, botulinum toxin injections and intrathecal baclofen have been used as treatment modalities. The selection of the most appropriate treatment modality by doctors treating patients with spasticity is critical. Furthermore, rehabilitation techniques, such as physiotherapy, occupational therapy, therapeutic electrical nerve stimulation, and orthosis, are useful as combination therapy for the treatment of spasticity. The purpose of this study was to outline the various modalities that are currently used for the treatment of spasticity. Regardless of the modality selected, it is imperative that treatment goals are carefully identified. The reduction of spasticity is not an appropriate treatment goal. Appropriate goals include improving gait, activities of daily living, and the quality of life.

Brain-computer interface with somatosensory feedback improves functional recovery from severe hemiplegia due to chronic stroke.

Recent studies have shown that scalp electroencephalogram (EEG) based brain-computer interface (BCI) has a great potential for motor rehabilitation in stroke patients with severe hemiplegia. However, key elements in BCI architecture for functional recovery has yet to be clear. We in this study focused on the type of feedback to the patients, which is given contingently to their motor-related EEG in a BCI context. The efficacy of visual and somatosensory feedbacks was compared by a two-group study with the chronic stroke patients who are suffering with severe motor hemiplegia. Twelve patients were asked an attempt of finger opening in the affected side repeatedly, and the event-related desynchronization (ERD) in EEG of alpha and beta rhythms was monitored over bilateral parietal regions. Six patients were received a simple visual feedback in which the hand open/grasp picture on screen was animated at eye level, following significant ERD. Six patients were received a somatosensory feedback in which the motor-driven orthosis was triggered to extend the paralyzed fingers from 90 to 50°. All the participants received 1-h BCI treatment with 12-20 training days. After the training period, while no changes in clinical scores and electromyographic (EMG) activity were observed in visual feedback group after training, voluntary EMG activity was newly observed in the affected finger extensors in four cases and the clinical score of upper limb function in the affected side was also improved in three participants in somatosensory feedback group. Although the present study was conducted with a limited number of patients, these results imply that BCI training with somatosensory feedback could be more effective for rehabilitation than with visual feedback. This pilot trial positively encouraged further clinical BCI research using a controlled design.