"Three-in-one": A Photoactivable Nanoplatform Evokes Anti-Immune Response by Inhibiting BRD4-cMYC-PDL1 Axis to Intensify Photo-Immunotherapy.

Combinatorial immuno-cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune-regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ-1) using polypyrrole/hyaluronic acid (PPyHA/JQ-1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near-infrared light, and laser-controlled JQ-1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ-1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ-1 in the tumor microenvironment (TME). Notably, the controlled release of JQ-1 substantially inhibits the expression of cancer-promoting genes. Furthermore, PPyHA/JQ-1 effectively suppresses the expression of programmed cell death ligand 1 (PD-L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ-1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor-immune response. Overall, "Three-in-one" immunotherapeutic photo-activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC.

Effect of 4-weeks exercise program using wearable hip-assist robot (EX1) in older adults: one group pre- and post- test.

BACKGROUND: Older adults have muscle loss and are at risk of falling. Recently, research in the healthcare field has been actively conducted, and Samsung Electronics has developed EX1, a hip joint assisted robot for exercise. This study aimed to verify the effect of a 4-week combined exercise program applying EX1 on older adults. METHODS: This study design was an evaluator-blinded, pre- and post-test. A total of 21 older adults performed an exercise program consisting of walking and fitness wearing EX1 for 50 min per session, 3 days a week during the 4-week exercise period. For comparison before and after participating in the exercise program, the spatio-temporal parameters, pelvic movement were analyzed by G-Walk, functional outcomes were evaluated by TUG, muscle power were evaluated by RUSI, and waist-hip ratio were analyzed by Inbody. All data were analyzed before and after exercise using paired t-test, and the statistical significance level was set at 0.05. RESULTS: In spatio-temporal parameters, stride length showed statistically significant improvements after exercise with EX1 (P < 0.01). Also, propulsion showed statistically significant improvements after exercise with EX1 (P < 0.01) Regarding changes of the gait posture, there was a statistically significant improvement in pelvic movement (P < 0.05). In the functional evaluation, the time required was statistically significantly reduced in the timed up and go test (P < 0.05). CONCLUSION: These results demonstrate that a 4-week exercise program with EX1 was effective in improving the functional gait of the elderly. However, because the participants were 21, it is difficult to generalize the results. TRIAL REGISTRATION: Clinical Research Information Service, KCT0007367. Registered 08/06/2022.

Comparative study of young-old and old-old people using functional evaluation, gait characteristics, and cardiopulmonary metabolic energy consumption.

BACKGROUND: Walking is an important factor in daily life. Among older adults, gait function declines with age. In contrast to the many studies revealing gait differences between young adults and older adults, few studies have further divided older adults into groups. The purpose of this study was to subdivide an older adult population by age to identify age-related differences in functional evaluation, gait characteristics and cardiopulmonary metabolic energy consumption while walking. METHODS: This was a cross-sectional study of 62 old adult participants who were classified into two age groups of 31 participants each as follows: young-old (65-74 years) and old-old (75-84 years) group. Physical functions, activities of daily living, mood state, cognitive function, quality of life, and fall efficacy were evaluated using the Short Physical Performance Battery (SPPB), Four-square Step Test (FSST), Timed Up and Go Test (TUG), Korean Version of the Modified Barthel Index, Geriatric Depression Scale (GDS), Korean Mini-mental State Examination, EuroQol-5 Dimensions (EQ-5D) questionnaire, and the Korean version of the Fall Efficacy Scale. A three-dimensional motion capture system (Kestrel Digital RealTime System®; Motion Analysis Corporation, Santa Rosa, CA, USA) and two force plates (TF-4060-B; Tec Gihan, Kyoto, Japan) were used to investigate spatiotemporal gait parameters (velocity, cadence, stride length, stride width, step length, single support, stance phase, and swing phase), kinematic variables (hip, knee, and ankle joint angles), and kinetic variables (hip, knee, and ankle joint moment and power) of gait. A portable cardiopulmonary metabolic system (K5; Cosmed, Rome, Italy) was used to measure cardiopulmonary energy consumption. RESULTS: The old-old group showed significantly lower SPPB, FSST, TUG, GDS-SF, and EQ-5D scores (p < 0.05). Among spatiotemporal gait parameters, velocity, stride length, and step length were significantly lower in the old-old group than in the young-old group (p < 0.05). Among the kinematic variables, the knee joint flexion angles during initial contact and terminal swing phase were significantly higher in the old-old than the young-old group (P < 0.05). The old-old group also showed a significantly lower ankle joint plantarflexion angle during the pre- and initial swing phases (P < 0.05). Among the kinetic variables, the hip joint flexion moment and knee joint absorption power in the pre-swing phase were significantly lower in the old-old than the young-old group (P < 0.05). CONCLUSION: This study demonstrated that participants 75-84 years of age had less functional gaits than their young-old counterparts (65-74 years old). As the walking pace of old-old people diminishes, driving strength to move ahead and pressure on the knee joint also tend to decrease together with stride length. These differences in gait characteristics according to age among older adults could improve our understanding of how aging causes variations in gait that increase the risk of falls. Older adults of different ages may require customized intervention plans, such as gait training methods, to prevent age-related falls. TRIAL REGISTRATION: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04723927 (26/01/2021).

Exercise with a wearable hip-assist robot improved physical function and walking efficiency in older adults.

Wearable assistive robotics has emerged as a promising technology to supplement or replace motor functions and to retrain people recovering from an injury or living with reduced mobility. We developed delayed output feedback control for a wearable hip-assistive robot, the EX1, to provide gait assistance. Our purpose in this study was to investigate the effects of long-term exercise with EX1 on gait, physical function, and cardiopulmonary metabolic energy efficiency in elderly people. This study used parallel experimental (exercise with EX1) and control groups (exercise without EX1). A total of 60 community-dwelling elderly persons participated in 18 exercise intervention sessions during 6 weeks, and all participants were assessed at 5 time points: before exercise, after 9 exercise sessions, after 18 sessions, and 1 month and 3 months after the last session. The spatiotemporal gait parameters, kinematics, kinetics, and muscle strength of the trunk and lower extremities improved more after exercise with EX1 than in that without EX1. Furthermore, the effort of muscles over the trunk and lower extremities throughout the total gait cycle (100%) significantly decreased after exercise with EX1. The net metabolic energy costs during walking significantly improved, and functional assessment scores improved more in the experimental group than in the control group. Our findings provide evidence supporting the application of EX1 in physical activity and gait exercise is effective to improve age-related declines in gait, physical function, and cardiopulmonary metabolic efficiency among older adults.

Functional Improvement and Satisfaction with a Wearable Hip Exoskeleton in Community-Living Adults.

Demand for wearable devices and supportive technology is growing as these devices have the potential to enhance physical function and quality of life in users. The purpose of this study was to investigate usability and satisfaction after performing functional and gait exercise with a wearable hip exoskeleton in community-living adults. A total of 225 adults residing in the local community participated in this study. All participants performed 40 min of exercise once with a wearable hip exoskeleton in various environments. The EX1, which functions as a wearable hip exoskeleton, was used. Physical function was assessed before and after exercise with the EX1. After completing exercise with the EX1, the usability and satisfaction questionnaires were evaluated. Gait speed, timed up and go test (TUG), and four square step test (FSST) showed statistically significant improvements after exercise with the EX1 in both groups (p < 0.05). In the 6 min walking test (6MWT), a significant increase was observed in the middle-aged group (p < 0.05). In the short physical performance battery (SPPB), there was a significant improvement in the old-aged group (p < 0.05). On the other hand, positive results in usability and satisfaction were noticed in both groups. These results demonstrate that a single session of exercise with the EX1 was effective in improving physical performance of both middle- and old-aged adults, with positive feedback from most of the participants.

A Smart Glove Digital System Promotes Restoration of Upper Limb Motor Function and Enhances Cortical Hemodynamic Changes in Subacute Stroke Patients with Mild to Moderate Weakness: A Randomized Controlled Trial.

This study was a randomized controlled trial to examine the effects of the RAPAEL® Smart Glove digital training system on upper extremity function and cortical hemodynamic changes in subacute stroke patients. Of 48 patients, 20 experimental and 16 controls completed the study. In addition to conventional occupational therapy (OT), the experimental group received game-based digital hand motor training with the RAPAEL® Smart Glove digital system, while the control group received extra OT for 30 min. The Fugl-Meyer assessment (UFMA) and Jebsen-Tayler hand function test (JTT) were assessed before (T0), immediately after (T1), and four weeks after intervention (T2). Cortical hemodynamics (oxyhemoglobin [OxyHb] concentration) were measured by functional near-infrared spectroscopy. The experimental group had significantly better improvements in UFMA (T1-T0 mean [SD]; Experimental 13.50 [7.49]; Control 8.00 [4.44]; p = 0.014) and JTT (Experimental 21.10 [20.84]; Control 5.63 [5.06]; p = 0.012). The OxyHb concentration change over the ipsilesional primary sensorimotor cortex during the affected wrist movement was greater in the experimental group (T1, Experimental 0.7943 × 10-4 µmol/L; Control -0.3269 × 10-4 µmol/L; p = 0.025). This study demonstrated a beneficial effect of game-based virtual reality training with the RAPAEL® Smart Glove digital system with conventional OT on upper extremity motor function in subacute stroke patients.

Effect of Exercise Using an Exoskeletal Hip-Assist Robot on Physical Function and Walking Efficiency in Older Adults.

Robotic technology has developed rapidly in recent years, and several robotic devices have been applied to improve physical, sensory, intellectual, psychological, and social functioning in the elderly and people with disabilities. In this study, we investigated the effects of EX1-assisted exercise in various environments on physical function, muscle strength, and walking efficiency in older adults. We designated four experimental conditions and randomly assigned participants to one of four groups: A (overground walking without an EX1), B (overground walking using the resistance mode of EX1), C (stair ascent using the assistance mode of EX1), and Group D (inclined treadmill walking using the assistance mode of EX1). A total of 60 community-dwelling elderly persons participated in 10 exercise intervention sessions for 4 weeks, and all participants were assessed before and after the exercise intervention. Physical function was measured by the 10-meter walk test for self-selected velocity (10MWT-SSV), short physical performance battery (SPPB), Berg balance scale (BBS), timed up and go (TUG), functional reach test (FRT), geriatric depression scale-short form (GDS-SF), and muscle strength of trunk and lower extremity. Cardiopulmonary metabolic energy efficiency was measured using a portable telemetric gas analyzer system. A significant increase in the 10MWT-SSV and TUG test was observed in groups B, C, and D. A statistically significant improvement in the SPPB and FRT was seen only in group D, and GDS-SF scores decreased significantly after exercise with an EX1 in groups B and D. Trunk and lower limb muscle strength increased more in the groups that exercised with EX1 assistance than those without an EX1, particularly in group B. The net metabolic energy costs and energy expenditure measurement during walking significantly improved in exercise groups C and D. The findings in this study support the application of the EX1 to physical activity and exercise to improve age-related changes in physical function, muscle strength, and walking efficiency among older adults. In addition, personalized exercise programs using different modes and training environments with an EX1 can enhance physical performance and walking efficiency in the elderly.

Highly Optimized Iron Oxide Embedded Poly(Lactic Acid) Nanocomposites for Effective Magnetic Hyperthermia and Biosecurity.

INTRODUCTION: Iron oxide magnetic nanoparticles (IONPs) have attracted considerable attention for various biomedical applications owing to their ease of synthesis, strong magnetic properties, and biocompatibility. In particular, IONPs can generate heat under an alternating magnetic field, the effects of which have been extensively studied for magnetic hyperthermia therapy. However, the development of IONPs with high heating efficiency, biocompatibility, and colloidal stability in physiological environments is still required for their safe and effective application in biomedical fields. METHODS: We synthesized magnetic IONP/polymer nanocomposites (MNCs) by embedding IONPs in a poly(L-lactic acid) (PLA) matrix via nanoemulsion. The IONP contents (Fe: 9-22 [w/w]%) in MNCs were varied to investigate their effects on the magnetic and hyperthermia performances based on their optimal interparticle interactions. Further, we explored the stability, cytocompatibility, biodistribution, and in vivo tissue compatibility of the MNCs. RESULTS: The MNCs showed enhanced heating efficiency with over two-fold increase compared to nonembedded bare IONPs. The relationship between the IONP content and heating performance in MNCs was nonmonotonous. The highest heating performance was obtained from MNC2, which contain 13% Fe (w/w), implying that interparticle interactions in MNCs can be optimized to achieve high heating performance. In addition, the MNCs exhibited good colloidal stability under physiological conditions and maintained their heating efficiency during 48 h of incubation in cell culture medium. Both in vitro and in vivo studies revealed excellent biocompatibility of the MNC. CONCLUSION: Our nanocomposites, comprising biocompatible IONPs and PLA, display improved heating efficiency, good colloidal stability, and cytocompatibility, and thus will be beneficial for diverse biomedical applications, including magnetic hyperthermia for cancer treatment.

A wearable electromyography-controlled functional electrical stimulation system improves balance, gait function, and symmetry in older adults.

BACKGROUND: Wearable technologies have been developed for healthy aging. The technology for electromyography (EMG)-controlled functional electrical stimulation (FES) systems has been developed, but research on how helpful it is in daily life has been insufficient. OBJECTIVE: The purpose of this study was to investigate the effect of the EMG-controlled FES system on muscle morphology, balance, and gait in older adults. METHODS: Twenty-nine older adults were evaluated under two randomly assigned conditions (non-FES and FES assists). Muscle morphology, balance, gait function, and muscle effort during gait were measured using ultrasonography, a physical test, a gait analysis system, and EMG. RESULTS: The EMG-controlled FES system improved gait speed by 11.1% and cadence by 15.6% (P< 0.01). The symmetry ratio of the bilateral gastrocnemius was improved by 9.9% in the stance phase and 11.8% in the swing phase (P< 0.05). The degrees of coactivation of the knee and ankle muscles were reduced by 45.1% and 50.5%, respectively (P< 0.05). Balance improved by 6-10.7% (P< 0.01). CONCLUSION: The EMG-controlled FES system is useful for balance and gait function by increasing muscle symmetry and decreasing muscle coactivation during walking in older adults.

Proof-of-Concept of a Sensor-Based Evaluation Method for Better Sensitivity of Upper-Extremity Motor Function Assessment.

In rehabilitation, the Fugl-Meyer assessment (FMA) is a typical clinical instrument to assess upper-extremity motor function of stroke patients, but it cannot measure fine changes of motor function (both in recovery and deterioration) due to its limited sensitivity. This paper introduces a sensor-based automated FMA system that addresses this limitation with a continuous rating algorithm. The system consists of a depth sensor (Kinect V2) and an algorithm to rate the continuous FM scale based on fuzzy inference. Using a binary logic based classification method developed from a linguistic scoring guideline of FMA, we designed fuzzy input/output variables, fuzzy rules, membership functions, and a defuzzification method for several representative FMA tests. A pilot trial with nine stroke patients was performed to test the feasibility of the proposed approach. The continuous FM scale from the proposed algorithm exhibited a high correlation with the clinician rated scores and the results showed the possibility of more sensitive upper-extremity motor function assessment.

Correlation between cardiopulmonary metabolic energy cost and lower-limb muscle activity during inclined treadmill gait in older adults.

BACKGROUND: Inclined walking requires more cardiopulmonary metabolic energy and muscle strength than flat-level walking. This study sought to investigate changes in lower-limb muscle activity and cardiopulmonary metabolic energy cost during treadmill walking with different inclination grades and to discern any correlation between these two measures in older adults. METHODS: Twenty-four healthy older adults (n = 11 males; mean age: 75.3 ± 4.0 years) participated. All participants walked on a treadmill that was randomly inclined at 0% (condition 1), 10% (condition 2), and 16% (condition 3) for five minutes each. Simultaneous measurements of lower-limb muscle activity and cardiopulmonary metabolic energy cost during inclined treadmill walking were collected. Measured muscles included the rectus abdominis (RA), erector spinae (ES), rectus femoris (RF), biceps femoris (BF), vastus medialis (VM), tibialis anterior (TA), medial head of the gastrocnemius (GCM), and soleus (SOL) muscles on the right side. RESULTS: As compared with 0% inclined treadmill gait, the 10% inclined treadmill gait increased the net cardiopulmonary metabolic energy cost by 22.9%, while the 16% inclined treadmill gait increased the net cardiopulmonary metabolic energy cost by 44.2%. In the stance phase, as the slope increased, activity was significantly increased in the RA, RF, VM, BF, GCM, and SOL muscles. In the swing phase, As the slope increased activity was significantly increased in the RA, RF, VM, BF, and TA muscles. SOL muscle activity was most relevant to the change in cardiopulmonary metabolic energy cost in the stance phase of inclined treadmill walking. The relationship between the increase in cardiopulmonary metabolic energy cost and changes in muscle activity was also significant in the VM, GCM, and RF. CONCLUSION: This study demonstrated that changes in SOL, VM, GCM, and RA muscle activity had a significant relationship with cardiopulmonary metabolic energy cost increment during inclined treadmill walking. These results can be used as basic data for various gait-training programs and as an indicator in the development of assistive algorithms of wearable walking robots for older adults. TRIAL REGISTRATION: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04614857 (05/11/2020).

The Heating Efficiency and Imaging Performance of Magnesium Iron Oxide@tetramethyl Ammonium Hydroxide Nanoparticles for Biomedical Applications.

Multifunctional magnetic nanomaterials displaying high specific loss power (SLP) and high imaging sensitivity with good spatial resolution are highly desired in image-guided cancer therapy. Currently, commercial nanoparticles do not sufficiently provide such multifunctionality. For example, Resovist® has good image resolution but with a low SLP, whereas BNF® has a high SLP value with very low image resolution. In this study, hydrophilic magnesium iron oxide@tetramethyl ammonium hydroxide nanoparticles were prepared in two steps. First, hydrophobic magnesium iron oxide nanoparticles were fabricated using a thermal decomposition technique, followed by coating with tetramethyl ammonium hydroxide. The synthesized nanoparticles were characterized using XRD, DLS, TEM, zeta potential, UV-Vis spectroscopy, and VSM. The hyperthermia and imaging properties of the prepared nanoparticles were investigated and compared to the commercial nanoparticles. One-dimensional magnetic particle imaging indicated the good imaging resolution of our nanoparticles. Under the application of a magnetic field of frequency 614.4 kHz and strength 9.5 kA/m, nanoparticles generated heat with an SLP of 216.18 W/g, which is much higher than that of BNF (14 W/g). Thus, the prepared nanoparticles show promise as a novel dual-functional magnetic nanomaterial, enabling both high performance for hyperthermia and imaging functionality for diagnostic and therapeutic processes.

Optimal stimulation site for rTMS to improve motor function: Anatomical hand knob vs. hand motor hotspot.

Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neuronal excitability of the human brain. Distant effects on contralateral corticomotor excitability can be exerted by interhemispheric modulation by low-frequency rTMS on ipsilateral hemisphere. To modulate corticospinal excitability, accurate determination of the stimulation site is important to maximize the effects of rTMS. In the present study, we investigated the difference in the distant effect of 1 Hz rTMS with respect to inducing functional improvement in the non-dominant hand by inhibiting the dominant hemisphere depending on cortical target areas. Ten healthy right-handed volunteers without any neurological disorders were enrolled. The anatomical hand knob (HK) identified from individual magnetic resonance imaging and the transcranial magnetic stimulation (TMS) induced hand motor hotspot (hMHS) by recording motor evoked potentials (MEPs) in the contralateral first dorsal interosseous muscle were determined. All participants underwent three conditions of 1 Hz rTMS on left hemisphere intervention; rTMS application over the HK, rTMS application over the hMHS, and sham-rTMS. Before and after each intervention, all participants undergone motor function assessments with their left hand. The cortical mapping showed that the hMHS was located anteriorly and laterally compared to the HK. Motor function tests showed the most significant improvements after the hMHS stimulation. When we compared the distant effects of target site on corticospinal excitability and motor behavior, delivering 1 Hz rTMS to the hMHS was more effective than delivering it to the HK for improving corticomotor excitability, motor skill, and dexterity. These results suggest that TMS-induced hMHS is an optimal target area to induce distant effect of low-frequency rTMS in motor function.

Comparison of hemodynamic changes after repetitive transcranial magnetic stimulation over the anatomical hand knob and hand motor hotspot: A functional near-infrared spectroscopy study.

BACKGROUND: Low-frequency rTMS can induce upregulation of excitability in the contralateral hemisphere by interhemispheric interaction. OBJECTIVE: The aim of this study was to compare the effects of interhemispheric modulation on hemodynamic changes after applying low-frequency rTMS over the anatomical hand knob (HK) and the hand motor hotspot (hMHS) in the dominant motor cortex. METHODS: Ten healthy right-handed participants without a history of neurological or psychiatric symptoms (five males; 29.8±2.8 years) participated in this single-blind, randomized, cross-over study. rTMS was applied under three conditions over the dominant (left) hemisphere for 20 minutes: 1) 1 Hz rTMS stimulation on the HK (HK-rTMS), 2) 1 Hz rTMS stimulation on the hMHS (hMHS-rTMS), and 3) sham stimulation (Sham-rTMS). For all participants, functional near-infrared spectroscopy (fNIRS) was applied for measurement of cerebral oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) concentration over the non-dominant (right) hemisphere during a serial reaction time task (SRTT) with the non-dominant (left) hand before and after each condition. RESULTS: The average coordinates of the hMHS (x = - 39.60 mm, y = - 17.11 mm, z = 66.40 mm) were anterior and lateral to the HK (x = - 36.72 mm, y = - 28.87 mm, z = 56.41 mm). In fNIRS time-series analysis, the integral value of oxyHb wassignificantly increased over the motor cortical region of the non-dominant hemisphere after the hMHS-rTMS compared with Sham-rTMS. The HK-rTMS also showed slight increment of oxyHb concentration but without statistical significance. The SPM group analysis showed greater magnitude of the activity in hMHS-rTMS than that of HK-rTMS after stimulation (p < 0.05). CONCLUSIONS: These results demonstrated an interhemispheric modulation effect of hemodynamic changes by 1 Hz rTMS. The hMHS produced a more robust modulation effect of 1 Hz rTMS on the contralateral hemisphere than did the HK. Therefore, the rTMS can be considered a better stimulation target than the HK.

Wearable hip-assist robot modulates cortical activation during gait in stroke patients: a functional near-infrared spectroscopy study.

BACKGROUND: Gait dysfunction is common in post-stroke patients as a result of impairment in cerebral gait mechanism. Powered robotic exoskeletons are promising tools to maximize neural recovery by delivering repetitive walking practice. OBJECTIVES: The purpose of this study was to investigate the modulating effect of the Gait Enhancing and Motivating System-Hip (GEMS-H) on cortical activation during gait in patients with chronic stroke. METHODS: Twenty chronic stroke patients performed treadmill walking at a self-selected speed either with assistance of GEMS-H (GEMS-H) or without assistance of GEMS-H (NoGEMS-H). Changes in oxygenated hemoglobin (oxyHb) concentration in the bilateral primary sensorimotor cortex (SMC), premotor cortices (PMC), supplemental motor areas (SMA), and prefrontal cortices (PFC) were recorded using functional near infrared spectroscopy. RESULTS: Walking with the GEMS-H promoted symmetrical SMC activation, with more activation in the affected hemisphere than in NoGEMS-H conditions. GEMS-H also decreased oxyHb concentration in the late phase over the ipsilesional SMC and bilateral SMA (P < 0.05). CONCLUSIONS: The results of the present study reveal that the GEMS-H promoted more SMC activation and a balanced activation pattern that helped to restore gait function. Less activation in the late phase over SMC and SMA during gait with GEMS-H indicates that GEMS-H reduces the cortical participation of stroke gait by producing rhythmic hip flexion and extension movement and allows a more coordinate and efficient gait patterns. Trial registration NCT03048968. Registered 06 Feb 2017.

Engineering Core-Shell Structures of Magnetic Ferrite Nanoparticles for High Hyperthermia Performance.

Magnetic ferrite nanoparticles (MFNs) with high heating efficiency are highly desirable for hyperthermia applications. As conventional MFNs usually show low heating efficiency with a lower specific loss power (SLP), extensive efforts to enhance the SLP of MFNs have been made by varying the particle compositions, sizes, and structures. In this study, we attempted to increase the SLP values by creating core-shell structures of MFNs. Accordingly, first we synthesized three different types of core ferrite nanoparticle of magnetite (mag), cobalt ferrite (cf) and zinc cobalt ferrite (zcf). Secondly, we synthesized eight bi-magnetic core-shell structured MFNs; Fe3O4@CoFe2O4 (mag@cf1, mag@cf2), CoFe2O4@Fe3O4 (cf@mag1, cf@mag2), Fe3O4@ZnCoFe2O4 (mag@zcf1, mag@zcf2), and ZnCoFe2O4@Fe3O4 (zcf@mag1, zcf@mag2), using a modified controlled co-precipitation process. SLP values of the prepared core-shell MFNs were investigated with respect to their compositions and core/shell dimensions while varying the applied magnetic field strength. Hyperthermia properties of the prepared core-shell MFNs were further compared to commercial magnetic nanoparticles under the safe limits of magnetic field parameters (<5 × 109 A/(m·s)). As a result, the highest SLP value (379.2 W/gmetal) was obtained for mag@zcf1, with a magnetic field strength of 50 kA/m and frequency of 97 kHz. On the other hand, the lowest SLP value (1.7 W/gmetal) was obtained for cf@mag1, with a magnetic field strength of 40 kA/m and frequency of 97 kHz. We also found that magnetic properties and thickness of the shell play critical roles in heating efficiency and hyperthermia performance. In conclusion, we successfully enhanced the SLP of MFNs by engineering their compositions and dimensions.

Photothermal Polymerization Using Graphene Oxide for Robust Hydrogelation with Various Light Sources.

Photopolymerization has been widely used for remote inducible hydrogelation with excellent spatiotemporal control. Recently, photothermal hydrogelation using near-infrared (NIR) light and photothermal agents has been developed showing remote hydrogelation ability with good biocompatibility and tissue penetration. However, the use of plasmonic nanoparticles (e.g., gold nanorods (GNRs)) still causes problems in reaction efficiency because hydrogelation is effective only when the wavelength of light is matched with the optical properties of the GNRs. Here, we demonstrated wavelength-independent photothermal hydrogelation using PEGylated graphene oxide (GO-PEG) that displays excellent heat generation from lights of a wide range of wavelengths. A sufficient increase in the temperature of the GO-PEG solution and the induction of thermal gelation of polyethylene diacrylate (PEGDA) by irradiation of various light sources (532, 785, and 980 nm) were demonstrated. Also, the GO-PEG-based photothermal hydrogelation of PEGDA was successfully employed for remote transdermal gel formation in vivo with 785 and 980 nm lasers. This wavelength-independent photothermal hydrogelation system will be useful for biomedical applications.

Training for Walking Efficiency With a Wearable Hip-Assist Robot in Patients With Stroke: A Pilot Randomized Controlled Trial.

Background and Purpose- The purpose of this study was to investigate the effects of gait training with a newly developed wearable hip-assist robot on locomotor function and efficiency in patients with chronic stroke. Methods- Twenty-eight patients with stroke with hemiparesis were initially enrolled, and 26 patients completed the randomized controlled trial (14 in the experimental and 12 in the control groups). The experimental group participated in a gait training program over a total of 10 sessions, including 5 treadmill sessions and 5 over-ground gait training sessions while wearing a hip-assist robot, the Gait Enhancing and Motivating System (GEMS, Samsung Advanced Institute of Technology, Suwon, Republic of Korea). The control group received gait training without Gait Enhancing and Motivating System. Primary outcome measured locomotor function and cardiopulmonary metabolic energy efficiency. Also, secondary outcome measured motor function and balance parameter. Results- Compared with the control group, the experimental group had significantly greater improvement in spatiotemporal gait parameters and muscle efforts after the training intervention (P<0.05). The net cardiopulmonary metabolic energy cost (mL·kg-1·min-1) was also reduced by 14.71% in the experimental group after the intervention (P<0.01). Significant group×time interactions were observed for all parameters (P<0.05). Cardiopulmonary metabolic efficiency was strongly correlated with gait symmetry ratio in the experimental group (P<0.01). Conclusions- Gait training with Gait Enhancing and Motivating System was effective for improving locomotor function and cardiopulmonary metabolic energy efficiency during walking in patients with stroke. These findings suggest that robotic locomotor training can be adopted for rehabilitation of patients with stroke with gait disorders. Clinical Trial Registration- URL: https://clinicaltrials.gov. Unique identifier: NCT02843828.

Synthesis of Magnetic Ferrite Nanoparticles with High Hyperthermia Performance via a Controlled Co-Precipitation Method.

Magnetic nanoparticles (MNPs) that exhibit high specific loss power (SLP) at lower metal content are highly desirable for hyperthermia applications. The conventional co-precipitation process has been widely employed for the synthesis of magnetic nanoparticles. However, their hyperthermia performance is often insufficient, which is considered as the main challenge to the development of practicable cancer treatments. In particular, ferrite MNPs have unique properties, such as a strong magnetocrystalline anisotropy, high coercivity, and moderate saturation magnetization, however their hyperthermia performance needs to be further improved. In this study, cobalt ferrite (CoFe2O4) and zinc cobalt ferrite nanoparticles (ZnCoFe2O4) were prepared to achieve high SLP values by modifying the conventional co-precipitation method. Our modified method, which allows for precursor material compositions (molar ratio of Fe+3:Fe+2:Co+2/Zn+2 of 3:2:1), is a simple, environmentally friendly, and low temperature process carried out in air at a maximum temperature of 60 °C, without the need for oxidizing or coating agents. The particles produced were characterized using multiple techniques, such as X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis spectroscopy), and a vibrating sample magnetometer (VSM). SLP values of the prepared nanoparticles were carefully evaluated as a function of time, magnetic field strength (30, 40, and 50 kA m-1), and the viscosity of the medium (water and glycerol), and compared to commercial magnetic nanoparticle materials under the same conditions. The cytotoxicity of the prepared nanoparticles by in vitro culture with NIH-3T3 fibroblasts exhibited good cytocompatibility up to 0.5 mg/mL. The safety limit of magnetic field parameters for SLP was tested. It did not exceed the 5 × 109 Am-1 s-1 threshold. A saturation temperature of 45 °C could be achieved. These nanoparticles, with minimal metal content, can ideally be used for in vivo hyperthermia applications, such as cancer treatments.

Modulation of Cortical Activity by High-Frequency Whole-Body Vibration Exercise: An fNIRS Study.

CONTEXT: Whole-body vibration (WBV) has shown many positive effects on the human body in rehabilitation and clinical settings in which vibration has been used to elicit muscle contractions in spastic and paretic muscles. OBJECTIVE: The purpose of this study was to investigate whether WBV exercise (WBVe) differently modulates the cortical activity associated with motor and prefrontal function based on its frequency. METHODS: A total of 18 healthy male adults (mean age: 25.3 [2.4] y) participated in this study and performed WBVe (Galileo Advanced plus; Novotec Medical, Pforzheim, Germany) under 3 different vibration frequency conditions (4-mm amplitude with 10-, 20-, and 27-Hz frequencies) and a control condition (0-mm amplitude with 0-Hz frequency). Each condition consisted of 2 alternating tasks (squatting and standing) every 30 seconds for 5 repetitions. All subjects performed the 4 conditions in a randomized order. MAIN OUTCOME MEASURE: Cortical activation during WBVe was measured by relative changes in oxygenated hemoglobin concentration over the primary motor cortex, premotor cortex, supplementary motor area, and prefrontal and somatosensory cortices using functional near-infrared spectroscopy. RESULTS: Oxygenated hemoglobin concentration was higher during the 27-Hz vibration condition than the control and 10-Hz vibration conditions. Specifically, these changes were pronounced in the bilateral primary motor cortex (P < .05) and right prefrontal cortex (P < .05). In contrast, no significant changes in oxygenated hemoglobin concentration were observed in any of the cortical areas during the 10-Hz vibration condition compared with the control condition. CONCLUSION: This study provides evidence that the motor network and prefrontal cortical areas of healthy adult males can be activated by 27-Hz WBVe. However, WBVe at lower frequencies did not induce significant changes in cortical activation.