Highlighting Unseen Activity Through 48-Hour Continuous Measurement in Subacute Stroke Rehabilitation: Preliminary Cohort Study.

BACKGROUND: Motor impairments not only lead to a significant reduction in patient activity levels but also trigger a further deterioration in motor function due to deconditioning, which is an issue that is particularly pronounced during hospitalization. This deconditioning can be countered by sustaining appropriate activity levels. Activities that occur outside of scheduled programs, often overlooked, are critical in this context. Wearable technology, such as smart clothing, provides a means to monitor these activities. OBJECTIVE: This study aimed to observe activity levels in patients who had strokes during the subacute phase, focusing on both scheduled training sessions and other nontraining times in an inpatient rehabilitation environment. A smart clothing system is used to simultaneously measure heart rate and acceleration, offering insights into both the amount and intensity of the physical activity. METHODS: In this preliminary cohort study, 11 individuals undergoing subacute stroke rehabilitation were enrolled. The 48-hour continuous measurement system, deployed at admission and reassessed 4 weeks later, monitored accelerometry data for physical activity (quantified with a moving SD of acceleration [MSDA]) and heart rate for intensity (quantified with percent heart rate reserve). The measurements were performed using a wearable activity monitoring system, the hitoe (NTT Corporation and Toray Industries, Inc) system comprising a measuring garment (wear or strap) with integrated electrodes, a data transmitter, and a smartphone. The Functional Independence Measure was used to assess the patients' daily activity levels. This study explored factors such as differences in activity during training and nontraining periods, correlations with activities of daily living (ADLs) and age, and changes observed after 4 weeks. RESULTS: A significant increase was found in the daily total MSDA after the 4-week program, with the average percent heart rate reserve remaining consistent. Physical activity during training positively correlated with ADL levels both at admission (ρ=0.86, P<.001) and 4 weeks post admission (ρ=0.96, P<.001), whereas the correlation between age and MSDA was not significant during training periods at admission (ρ=-0.41, P=.21) or 4 weeks post admission (ρ=-0.25, P=.45). Conversely, nontraining activity showed a negative correlation with age, with significant negative correlations with age at admission (ρ=-0.82, P=.002) and 4 weeks post admission (ρ=-0.73, P=.01). CONCLUSIONS: Inpatient rehabilitation activity levels were positively correlated with ADL levels. Further analysis revealed a strong positive correlation between scheduled training activities and ADL levels, whereas nontraining activities showed no such correlation. Instead, a negative correlation between nontraining activities and age was observed. These observations suggest the importance of providing activity opportunities for older patients, while it may also suggest the need for adjusting the activity amount to accommodate the potentially limited fitness levels of this demographic. Future studies with larger patient groups are warranted to validate and further elucidate these findings.

Variational autoencoder-based neural electrocardiogram synthesis trained by FEM-based heart simulator.

Background: For comprehensive electrocardiogram (ECG) synthesis, a recent promising approach has been based on a heart model with physical and chemical cardiac parameters. However, the problem is that such approach requires a high-cost and limited environment using supercomputers owing to the massive computation. Objective: The purpose of this study is to develop an efficient method for synthesizing 12-lead ECG signals from cardiac parameters. Methods: The proposed method is based on a variational autoencoder (VAE). The encoder and decoder of the VAE are conditioned by the cardiac parameters so that it can model the relationship between the ECG signals and the cardiac parameters. The training data are produced by a comprehensive, finite element method (FEM)-based heart simulator. New ECG signals can then be synthesized by inputting the cardiac parameters into the trained VAE decoder without relying on enormous computational resources. We used 2 metrics to evaluate the quality of ECG signals synthesized by the proposed model. Results: Experimental results showed that the proposed model synthesized adequate ECG signals while preserving empirically important feature points and the overall signal shapes. We also explored the optimal model by varying the number of layers and the size of latent variables in the proposed model that balances the model complexity and the simulation accuracy. Conclusion: The proposed method has the potential to become an alternative to computationally expensive FEM-based heart simulators. It is able to synthesize ECGs from various cardiac parameters within seconds on a personal laptop computer.

Ensemble averaging for categorical variables: Validation study of imputing lost data in 24-h recorded postures of inpatients.

Acceleration sensors are widely used in consumer wearable devices and smartphones. Postures estimated from recorded accelerations are commonly used as features indicating the activities of patients in medical studies. However, recording for over 24 h is more likely to result in data losses than recording for a few hours, especially when consumer-grade wearable devices are used. Here, to impute postures over a period of 24 h, we propose an imputation method that uses ensemble averaging. This method outputs a time series of postures over 24 h with less lost data by calculating the ratios of postures taken at the same time of day during several measurement-session days. Whereas conventional imputation methods are based on approaches with groups of subjects having multiple variables, the proposed method imputes the lost data variables individually and does not require other variables except posture. We validated the method on 306 measurement data from 99 stroke inpatients in a hospital rehabilitation ward. First, to classify postures from acceleration data measured by a wearable sensor placed on the patient's trunk, we preliminary estimated possible thresholds for classifying postures as 'reclining' and 'sitting or standing' by investigating the valleys in the histogram of occurrences of trunk angles during a long-term recording. Next, the imputations of the proposed method were validated. The proposed method significantly reduced the missing data rate from 5.76% to 0.21%, outperforming a conventional method.

Prediction of stroke patients' bedroom-stay duration: machine-learning approach using wearable sensor data.

Background: The importance of being physically active and avoiding staying in bed has been recognized in stroke rehabilitation. However, studies have pointed out that stroke patients admitted to rehabilitation units often spend most of their day immobile and inactive, with limited opportunities for activity outside their bedrooms. To address this issue, it is necessary to record the duration of stroke patients staying in their bedrooms, but it is impractical for medical providers to do this manually during their daily work of providing care. Although an automated approach using wearable devices and access points is more practical, implementing these access points into medical facilities is costly. However, when combined with machine learning, predicting the duration of stroke patients staying in their bedrooms is possible with reduced cost. We assessed using machine learning to estimate bedroom-stay duration using activity data recorded with wearable devices. Method: We recruited 99 stroke hemiparesis inpatients and conducted 343 measurements. Data on electrocardiograms and chest acceleration were measured using a wearable device, and the location name of the access point that detected the signal of the device was recorded. We first investigated the correlation between bedroom-stay duration measured from the access point as the objective variable and activity data measured with a wearable device and demographic information as explanatory variables. To evaluate the duration predictability, we then compared machine-learning models commonly used in medical studies. Results: We conducted 228 measurements that surpassed a 90% data-acquisition rate using Bluetooth Low Energy. Among the explanatory variables, the period spent reclining and sitting/standing were correlated with bedroom-stay duration (Spearman's rank correlation coefficient (R) of 0.56 and -0.52, p < 0.001). Interestingly, the sum of the motor and cognitive categories of the functional independence measure, clinical indicators of the abilities of stroke patients, lacked correlation. The correlation between the actual bedroom-stay duration and predicted one using machine-learning models resulted in an R of 0.72 and p < 0.001, suggesting the possibility of predicting bedroom-stay duration from activity data and demographics. Conclusion: Wearable devices, coupled with machine learning, can predict the duration of patients staying in their bedrooms. Once trained, the machine-learning model can predict without continuously tracking the actual location, enabling more cost-effective and privacy-centric future measurements.

Validity of trunk acceleration measurement with a chest-worn monitor for assessment of physical activity intensity.

BACKGROUND: Recent advancements in wearable technology have enabled easy measurement of daily activities, potentially applicable in rehabilitation practice for various purposes such as maintaining and increasing patients' activity levels. In this study, we aimed to examine the validity of trunk acceleration measurement using a chest monitor embedded in a smart clothing system ('hitoe' system), an emerging wearable system, in assessing the physical activity in an experimental setting with healthy subjects (Study 1) and in a clinical setting with post-stroke patients (Study 2). METHODS: Study 1 involved the participation of 14 healthy individuals. The trunk acceleration, heart rate (HR), and oxygen consumption were simultaneously measured during treadmill testing with a Bruce protocol. Trunk acceleration and HR were measured using the "hitoe" system, a smart clothing system with embedded chest sensors. Expiratory gas analysis was performed to measure oxygen consumption. Three parameters, moving average (MA), moving standard deviation (MSD), and moving root mean square (RMS), were calculated from the norm of the trunk acceleration. The relationships between these accelerometer-based parameters and oxygen consumption-based physical activity intensity measured with the percent VO2 reserve (%VO2R) were examined. In Study 2, 48 h of simultaneous measurement of trunk acceleration and heart rate-based physical activity intensity in terms of percent heart rate reserve (%HRR) was conducted with the "hitoe" system in 136 post-stroke patients. RESULTS: The values of MA, MSD, RMS, and %VO2R were significantly different between levels 1, 2, 3, and 4 in the Bruce protocol (P < 0.01). The average coefficients of determination for individual regression for %VO2R versus MA, %VO2R versus MSD, and %VO2R versus RMS were 0.89 ± 0.05, 0.96 ± 0.03, and 0.91 ± 0.05, respectively. Among the parameters examined, MSD showed the best correlation with %VO2R, indicating high validity of the parameter for assessing physical activity intensity. The 48-h measurement of MSD and %HRR in post-stroke patients showed significant within-individual correlation (P < 0.05) in 131 out of 136 patients (correlation coefficient: 0.60 ± 0.16). CONCLUSIONS: The results support the validity of the MSD calculated from the trunk acceleration measured with a smart clothing system in assessing the physical activity intensity. TRIAL REGISTRATION: UMIN000034967. Registered 21 November 2018 (retrospectively registered).

Novel lateral transfer assist robot decreases the difficulty of transfer in post-stroke hemiparesis patients: a pilot study.

PURPOSE: The purpose of this study was to clarify whether the novel lateral transfer assist robot facilitates easier transfers compared with a wheelchair in post-stroke hemiparesis patients. METHODS: This cross-sectional study enrolled 20 post-stroke hemiparesis patients, and the task difficulty of transfers was compared between a wheelchair and lateral transfer assist robot. All participants were asked to transfer from either wheelchair or lateral transfer assist robot to a platform table and back. The primary outcome was the transfer score of the Functional Independence Measure. The secondary outcome was the time required for transfer. RESULTS: The transfer score of the Functional Independence Measure was significantly higher with lateral transfer assist robot than with wheelchair (p < .001). The transfer times from these devices to a platform table and back showed no significant differences (to device from platform table: 7.8 s, lateral transfer assist robot vs 7.6 s, wheelchair, p > .05: device to platform table: 7.1 s, lateral transfer assist robot vs 8.0 s, wheelchair, p > .05). CONCLUSIONS: Transfer with a lateral transfer assist robot is easier than with wheelchair and facilitates independence in post-stroke hemiparesis patients.IMPLICATIONS FOR REHABILITATIONTransfer skill influences the functional independence and quality of life of a wheelchair userA novel structural mobility device-the lateral transfer assist robot (LTAR)-can facilitate transfersThe LTAR could improve the degree of independence for transfers than the wheelchair, without any time loss, in post-stroke hemiparesis patientsThe LTAR could potentially reduce the risk for falls in various medical and care facilities.

Validation of wearable textile electrodes for ECG monitoring.

A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.

Cell Assembly in Self-foldable Multi-layered Soft Micro-rolls.

Multi-layered thin films with heterogeneous mechanical properties can be spontaneously transformed to realise various three-dimensional (3D) geometries. Here, we describe micro-patterned all-polymer films called micro-rolls that we use for encapsulating, manipulating, and observing adherent cells in vitro. The micro-rolls are formed of twin-layered films consisting of two polymers with different levels of mechanical stiffness; therefore they can be fabricated by using the strain engineering and a self-folding rolling process. By controlling the strain of the films geometrically, we can achieve 3D tubular architectures with controllable diameters. Integration with a batch release of sacrificial hydrogel layers provides a high yield and the biocompatibility of the micro-rolls with any length in the release process without cytotoxicity. Thus, the multiple cells can be wrapped in individual micro-rolls and artificially reconstructed into hollow or fibre-shaped cellular 3D constructs that possess the intrinsic morphologies and functions of living tissues. This system can potentially provide 3D bio-interfaces such as those needed for reconstruction and assembly of functional tissues and implantable tissue grafts.

Time-lapse imaging of morphological changes in a single neuron during the early stages of apoptosis using scanning ion conductance microscopy.

Apoptosis plays an important role in many physiologic and pathologic conditions. The biochemical and morphological characteristics of apoptosis including cellular volume decrease, cell membrane blebbing, and phosphatidylserine translocation from the inner to the outer leaflet of the cell membrane are considered important events for phagocyte detection. Despite its importance, the relationship between the biological and morphological changes in a living cell has remained controversial. Scanning ion conductance microscopy is a suitable technique for investigating a series of these changes, because it allows us to observe the morphology of living cells without any mechanical interactions between the probe and the sample surface with a high resolution. Here, we investigated the biochemical and morphological changes in single neurons during the early stages of apoptosis, including apoptotic volume decrease, membrane blebbing and phosphatidylserine translocation, by using scanning ion conductance microscopy. Time-course imaging of apoptotic neurons showed there was a reduction in apoptotic volume after exposure to staurosporine and subsequent membrane bleb formation, which has a similar onset time to phosphatidylserine translocation. Our results show that a reduction in cellular volume is one of the earliest morphological changes in apoptosis, and membrane blebbing and phosphatidylserine translocation occur as subsequent biological and morphological changes. This is the first report to describe this series of morphological and biochemical changes ranging from an apoptotic volume decrease to membrane blebbing and PS translocation by scanning ion conductance microscopy (SICM). This new and direct imaging technique will provide new insight into the relationship between biochemical events inside a cell and cellular morphological changes.

[Role of magnesium in nerve tissue].

The role of magnesium on nerve tissue was discussed. Two main topics of "magnesium and neural activity" and "magnesium-therapy and brain neurons" were described together with introducing our research on rat cultured neurons of cortex and hippocampus.

Conductive polymer combined silk fiber bundle for bioelectrical signal recording.

Electrode materials for recording biomedical signals, such as electrocardiography (ECG), electroencephalography (EEG) and evoked potentials data, are expected to be soft, hydrophilic and electroconductive to minimize the stress imposed on living tissue, especially during long-term monitoring. We have developed and characterized string-shaped electrodes made from conductive polymer with silk fiber bundles (thread), which offer a new biocompatible stress free interface with living tissue in both wet and dry conditions.An electroconductive polyelectrolyte, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was electrochemically combined with silk thread made from natural Bombyx mori. The polymer composite 280 µm thread exhibited a conductivity of 0.00117 S/cm (which corresponds to a DC resistance of 2.62 Mohm/cm). The addition of glycerol to the PEDOT-PSS silk thread improved the conductivity to 0.102 S/cm (20.6 kohm/cm). The wettability of PEDOT-PSS was controlled with glycerol, which improved its durability in water and washing cycles. The glycerol treated PEDOT-PSS silk thread showed a tensile strength of 1000 cN in both wet and dry states. Without using any electrolytes, pastes or solutions, the thread directly collects electrical signals from living tissue and transmits them through metal cables. ECG, EEG, and sensory evoked potential (SEP) signals were recorded from experimental animals by using this thread placed on the skin. PEDOT-PSS silk glycerol composite thread offers a new class of biocompatible electrodes in the field of biomedical and health promotion that does not induce stress in the subjects.

Conditioning lesions before or after spinal cord injury recruit broad genetic mechanisms that sustain axonal regeneration: superiority to camp-mediated effects.

Previous studies indicate that peripheral nerve conditioning lesions significantly enhance central axonal regeneration via modulation of cAMP-mediated mechanisms. To gain insight into the nature and temporal dependence of neural mechanisms underlying conditioning lesion effects on central axonal regeneration, we compared the efficacy of peripheral sciatic nerve crush lesions to cAMP elevations (in lumbar dorsal root ganglia) on central sensory axonal regeneration when administered either before or after cervical spinal cord lesions. We found significantly greater effects of conditioning lesions compared to cAMP elevations on central axonal regeneration when combined with cellular grafts at the lesion site and viral neurotrophin delivery; further, these effects persisted whether conditioning lesions were applied prior to or shortly after spinal cord injury. Indeed, conditioning lesions recruited extensively greater sets of genetic mechanisms of possible relevance to axonal regeneration compared to cAMP administration, and sustained these changes for significantly greater time periods through the post-lesion period. We conclude that cAMP-mediated mechanisms account for only a portion of the potency of conditioning lesions on central axonal regeneration, and that recruitment of broader genetic mechanisms can extend the effect and duration of cellular events that support axonal growth.

Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury.

Despite advances in promoting axonal regeneration after acute spinal cord injury (SCI), elicitation of bridging axon regeneration after chronic SCI remains a formidable challenge. We report that combinatorial therapies administered 6 weeks, and as long as 15 months, after SCI promote axonal regeneration into and beyond a midcervical lesion site. Provision of peripheral nerve conditioning lesions, grafts of marrow stromal cells, and establishment of NT-3 gradients supports bridging regeneration. Controls receiving partial components of the full combination fail to exhibit bridging. Notably, intraneuronal molecular mechanisms recruited by delayed therapies mirror those of acute injury, including activation of transcriptional activators and regeneration-associated genes. Collectively, these findings provide evidence that regeneration is achievable at unprecedented postinjury time points.

Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.

Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer's disease. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer's disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer's disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer's disease.

High affinity D- and L-serine transporter Asc-1: cloning and dendritic localization in the rat cerebral and cerebellar cortices.

System asc transporter Asc-1, expressed in the brain, transports D- and L-serine with high affinity. To determine the localization of Asc-1 in the rat brain, we isolated a cDNA for the rat orthologue of Asc-1. The encoded protein designated as rAsc-1 (rat Asc-1) exhibited 98% sequence identity to mouse Asc-1 (mAsc-1). Based on amino acid sequences of rAsc-1 and mAsc-1, two polyclonal antibodies against Asc-1 were generated and used for the immunohistochemical analysis on the cerebral and cerebellar cortices of rats and mice. Asc-1 immunoreactivity was detected in neurons, including cerebellar Purkinje neurons and pyramidal neurons in the neocortex and hippocampus. It was clearly localized in dendrites as well as somata. The localization of Asc-1 in brain suggests the significant contribution of Asc-1 to amino acid mobilization in brains including the synaptic clearance of D-serine and the neuronal uptake of L-serine that is essential for survival and dendrite growth of Purkinje neurons in particular.

Real-time measurement of nitric oxide by luminol-hydrogen peroxide reaction in crystalloid perfused rat heart.

The objective of this study was to develop an assay system that allows continuous monitoring of nitric oxide (NO) released from crystalloid perfused hearts. We utilized chemiluminescence reaction between NO and luminol-H(2)O(2) to quantify the NO level in coronary effluent. Isolated rat hearts were subjected to ordinary Langendorff's perfusion, and the right ventricle was cannulated to sample coronary effluent. After equilibration, the coronary flow rate was set constant and the hearts were paced at 300 bpm. Coronary effluent was continuously sampled and mixed with the chemiluminescent probe containing 0.018 mmol/l luminol plus 10 mmol/l H(2)O(2). Chemiluminescence from the mixture of coronary effluent and the probe was continuously measured. NO concentration was calibrated by various concentrations (0.5-400 pmol/l) of standard NO solution. The lower detection limit of NO was 1 pmol/l. Basal NO release from isolated perfused rat heart was 0.41 +/- 0.17 pmol/min/g of heart weight, and that was significantly suppressed by 0.1 mmol/l of L-NAME to 0.18 +/- 0.10 pmol/min/g of heart weight (n = 7). Application of 0.1 and 0.3 micromol/l acetylcholine increased NO level in the coronary effluent, in a concentration-dependent manner, from 6.6 +/- 1.7 in a baseline condition to 16.3 +/- 7.4 and 30.3 +/- 16.1 pmol/l at each peak, respectively. Thrombin at 1 and 10 U/ml also increased NO level from 17.6 +/- 4.3 in control to 35.5 +/- 10.4 and 48.7 +/- 8.7 pmol/l at each peak, respectively (n = 7). Thus, this assay system is applicable to the continuous real-time measurement of NO released from crystalloid perfused hearts, and it may be useful for the study of physiological or pathophysiological role of NO in coronary circulation.

Activation of protein kinase A by nitric oxide in cultured dorsal root ganglion neurites of the rat, examined by a fluorescence probe, ARII.

To study the roles of nitric oxide (NO) in growth of nerve fibers, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamine (NOR3), an NO-donor, was applied to cultured dorsal root ganglion (DRG) neurites from a micropipette. Ejection of a small volume of 1 mM NOR3 solution (not more than 1 pl/s) from a micropipette to terminal branches of neurites caused enlargement of the neurites, and often, elongation of their growth cones. This neurite enlargement was blocked by inhibitors for soluble guanylate cyclase. The neurite enlargement did not occur when protein kinase A (PKA) was inhibited. To prove that NOR3 activated PKA, we introduced a fluorescence peptide probe, ARII that reduces its fluorescence by activated PKA, to monitor PKA activity in DRG neurites. ARII fluorescence was reduced by NOR3, which was not observed when PKA was inhibited by its specific inhibitors. These indicated that PKA was indeed activated by NO. To examine whether the PKA activation is due to inhibition of phosphodiesterase III (PDE III) by cyclic GMP, we applied PDE III-specific inhibitors and found that the inhibitions activated PKA. Since PKA regulates various neuronal functions, our finding that NO activates PKA is important to understand roles of NO in nerve fibers.