Liquid-Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics.

Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are increasingly being shown to play major roles in cellular self-organization dynamics in health and disease. It is well established that macromolecular crowding has a profound impact on protein interactions, particularly those that lead to LLPS. Although synthetic crowding agents are used during in vitro LLPS experiments, they are considerably different from the highly crowded nucleo-/cytoplasm and the effects of in vivo crowding remain poorly understood. In this work, we applied computational modeling to investigate the effects of macromolecular crowding on LLPS. To include biologically relevant LLPS dynamics, we extended the conventional Cahn-Hilliard model for phase separation by coupling it to experimentally derived macromolecular crowding dynamics and state-dependent reaction kinetics. Through extensive field-theoretic computer simulations, we show that the inclusion of macromolecular crowding results in late-stage coarsening and the stabilization of relatively smaller condensates. At a high crowding concentration, there is an accelerated growth and late-stage arrest of droplet formation, effectively resulting in anomalous labyrinthine morphologies akin to protein gelation observed in experiments. These results not only elucidate the crowder effects observed in experiments, but also highlight the importance of including state-dependent kinetics in LLPS models, and may help in designing further experiments to probe the intricate roles played by LLPS in self-organization dynamics of cells.

Patterned thin metal film for the lateral resolution measurement of photoacoustic tomography.

BACKGROUND: Image quality assessment method of photoacoustic tomography has not been completely standardized yet. Due to the combined nature of photonic signal generation and ultrasonic signal transmission in biological tissue, neither optical nor ultrasonic traditional methods can be used without modification. An optical resolution measurement technique was investigated for its feasibility for resolution measurement of photoacoustic tomography. METHODS: A patterned thin metal film deposited on silica glass provides high contrast in optical imaging due to high reflectivity from the metal film and high transmission from the glass. It provides high contrast when it is used for photoacoustic tomography because thin metal film can absorb pulsed laser energy. An US Air Force 1951 resolution target was used to generate patterned photoacoustic signal to measure the lateral resolution. Transducer with 2.25 MHz bandwidth and a sample submerged in water and gelatinous block were tested for lateral resolution measurement. RESULTS: Photoacoustic signal generated from a thin metal film deposited on a glass can propagate along the surface or through the surrounding medium. First, a series of experiments with tilted sample confirmed that the measured photoacoustic signal is what is propagating through the medium. Lateral resolution of the photoacoustic tomography system was successfully measured for water and gelatinous block as media: 0.33 mm and 0.35 mm in water and gelatinous material, respectively, when 2.25 MHz transducer was used. Chicken embryo was tested for biomedical applications. CONCLUSIONS: A patterned thin metal film sample was tested for its feasibility of measuring lateral resolution of a photoacoustic tomography system. Lateral resolutions in water and gelatinous material were successfully measured using the proposed method. Measured resolutions agreed well with theoretical values.

Miniaturized optimal incident light angle-fitted dark field system for contrast-enhanced real-time monitoring of 2D/3D-projected cell motions.

In the field of biology, dark field microscopy provides superior insight into cells and subcellular structures. However, most dark field microscopes are equipped with a dark field filter and a light source on a 2D-based specimen, so only a flat sample can be observed in a limited space. We propose a compact cell monitoring system with built-in dark field filter with an optimized incident angle of the light source to provide real-time cell imaging and spatial cell monitoring for long-term free from phototoxicity. 2D projection imaging was implemented using a modular condenser lens to acquire high-contrast images. This enabled the long-term monitoring of cells, and the real-time monitoring of cell division and death. This system was able to image, by 2D projection, cells on the surface thinly coated with multiwalled carbon nanotubes, as well as living cells that migrated along the surface of glass beads and hydrogel droplets with a diameter of about 160 µm. The optimal incident light angle-fitted dark field system combines high-contrast imaging sensitivity and high spatial resolution to even image cells on 3D surfaces.

Non-invasive algorithm for bowel motility estimation using a back-propagation neural network model of bowel sounds.

BACKGROUND: Radiological scoring methods such as colon transit time (CTT) have been widely used for the assessment of bowel motility. However, these radiograph-based methods need cumbersome radiological instruments and their frequent exposure to radiation. Therefore, a non-invasive estimation algorithm of bowel motility, based on a back-propagation neural network (BPNN) model of bowel sounds (BS) obtained by an auscultation, was devised. METHODS: Twelve healthy males (age: 24.8 ± 2.7 years) and 6 patients with spinal cord injury (6 males, age: 55.3 ± 7.1 years) were examined. BS signals generated during the digestive process were recorded from 3 colonic segments (ascending, descending and sigmoid colon), and then, the acoustical features (jitter and shimmer) of the individual BS segment were obtained. Only 6 features (J1, 3, J3, 3, S1, 2, S2, 1, S2, 2, S3, 2), which are highly correlated to the CTTs measured by the conventional method, were used as the features of the input vector for the BPNN. RESULTS: As a results, both the jitters and shimmers of the normal subjects were relatively higher than those of the patients, whereas the CTTs of the normal subjects were relatively lower than those of the patients (p < 0.01). Also, through k-fold cross validation, the correlation coefficient and mean average error between the CTTs measured by a conventional radiograph and the values estimated by our algorithm were 0.89 and 10.6 hours, respectively. CONCLUSIONS: The jitter and shimmer of the BS signals generated during the peristalsis could be clinically useful for the discriminative parameters of bowel motility. Also, the devised algorithm showed good potential for the continuous monitoring and estimation of bowel motility, instead of conventional radiography, and thus, it could be used as a complementary tool for the non-invasive measurement of bowel motility.

Axial-scanning low-coherence interferometer method for noncontact thickness measurement of biological samples.

We investigated a high-precision optical method for measuring the thickness of biological samples regardless of their transparency. The method is based on the precise measurement of optical path length difference of the end surfaces of objects, using a dual-arm axial-scanning low-coherence interferometer. This removes any consideration of the shape, thickness, or transparency of testing objects when performing the measurement. Scanning the reference simplifies the measurement setup, resulting in unambiguous measurement. Using a 1310 nm wavelength superluminescent diode, with a 65 nm bandwidth, the measurement accuracy was as high as 11.6 µm. We tested the method by measuring the thickness of both transparent samples and nontransparent soft biological tissues.

Tumor-Targeting H2O2-Responsive Photosensitizing Nanoparticles with Antiangiogenic and Immunogenic Activities for Maximizing Anticancer Efficacy of Phototherapy.

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) uses photosensitizers and light to kill cancer cells and has become a promising therapeutic modality because of advantages such as minimal invasiveness and high cancer selectivity. However, PTT or PDT as a single treatment modality has insufficient therapeutic efficacy. Moreover, oxygen consumption by PDT activates angiogenic factors and leads to cancer recurrence and progression. Therefore, the therapeutic outcomes of phototherapy would be maximized by employing photosensitizers for concurrent PTT and PDT and suppressing angiogenic factors. Therefore, integrating photosensitive agents and antiangiogenic agents in a single nanoplatform would be a promising strategy to maximize the therapeutic efficacy of phototherapy. In this study, we developed hyaluronic acid-coated fluorescent boronated polysaccharide (HA-FBM) nanoparticles as a combination therapeutic agent for phototherapy and antiangiogenic therapy. Upon a single near-infrared laser irradiation, HA-FBM nanoparticles generated heat and singlet oxygen simultaneously to kill cancer cells and also induced immunogenic cancer cell death. Beside their fundamental roles as photosensitizers, HA-FBM nanoparticles exerted antiangiogenic effects by suppressing the vascular endothelial growth factor (VEGF) and cancer cell migration. In a mouse xenograft model, intravenously injected HA-FBM nanoparticles targeted tumors by binding CD44-overexpressing cancer cells and suppressed angiogenic VEGF expression. Upon laser irradiation, HA-FBM nanoparticles remarkably eradicated tumors and increased anticancer immunity. Given their synergistic effects of phototherapy and antiangiogenic therapy from tumor-targeting HA-FBM nanoparticles, we believe that integrating the photosensitizers and antiangiogenic agents into a single nanoplatform presents an attractive strategy to maximize the anticancer therapeutic efficacy of phototherapy.

Stimulus-activatable echogenic maltodextrin nanoparticles as nanotheranostic agents for peripheral arterial disease.

Reactive oxygen species (ROS) are closely related with various pathological disorders. Therefore, real-time detection of ROS is essential for understanding the procedure of diseases and diagnosing the accurate lesion sites. Hydrogen peroxide (H2O2) accounts for a large portion of ROS and has a longer half-life than other ROS, which makes it a highly promising diagnostic and therapeutic biomarker. In this work, we developed H2O2-activatable CO2 bubble generating indocyanine green-loaded boronated maltodextrin (ICG-BM) nanoparticles for imaging and therapy of peripheral arterial disease. ICG-BM nanoparticles displayed increasing fluorescence, ultrasound and photoacoustic signals in H2O2-triggered manners and exerted significant anti-inflammatory and proangiogenic effects in H2O2-stimulated vascular endothelial cells. In mouse models of hindlimb ischemia, ICG-BM nanoparticles also showed H2O2-triggered amplification of fluorescence, ultrasound and photoacoustic signals in the ischemic hindlimb muscles. ICG-BM nanoparticles also significantly reduced the level of overproduced H2O2 and exerted highly potent anti-inflammatory and proangiogenic activities in the ischemic tissues. We therefore believe that pathological stimulus-activatable echogenic ICG-BM nanoparticles provide a new avenue for imaging and treatment of peripheral arterial disease.

Assessment of Electrocardiogram Rhythms by GoogLeNet Deep Neural Network Architecture.

The aim of this study is to design GoogLeNet deep neural network architecture by expanding the kernel size of the inception layer and combining the convolution layers to classify the electrocardiogram (ECG) beats into a normal sinus rhythm, premature ventricular contraction, atrial premature contraction, and right/left bundle branch block arrhythmia. Based on testing MIT-BIH arrhythmia benchmark databases, the scope of training/test ECG data was configured by covering at least three and seven R-peak features, and the proposed extended-GoogLeNet architecture can classify five distinct heartbeats; normal sinus rhythm (NSR), premature ventricular contraction (PVC), atrial premature contraction (APC), right bundle branch block (RBBB), and left bundle brunch block(LBBB), with an accuracy of 95.94%, an error rate of 4.06%, a maximum sensitivity of 96.9%, and a maximum positive predictive value of 95.7% for judging a normal or an abnormal beat with considering three ECG segments; an accuracy of 98.31%, a sensitivity of 88.75%, a specificity of 99.4%, and a positive predictive value of 94.4% for classifying APC from NSR, PVC, APC beats, whereas the error rate for misclassifying APC beat was relative low at 6.32%, compared with previous research efforts.

Ultrasound imaging and on-demand therapy of peripheral arterial diseases using H2O2-Activated bubble generating anti-inflammatory polymer particles.

Muscles of peripheral artery disease (PAD) patients are under oxidative stress associated with a significantly elevated level of reactive oxygen species (ROS) including hydrogen peroxide (H2O2). Curcumin is a major active constituent of turmeric and is well known for its highly potent antioxidant, anti-inflammatory and angiogenic effects. We previously reported antioxidant vanillyl alcohol-incorporated copolyoxalate (PVAX) which is designed to rapidly scavenge H2O2 and release bioactive vanillyl alcohol and CO2 in a H2O2-triggered manner. In this work, we developed curcumin-loaded PVAX (CUR-PVAX) nanoparticles as contrast-enhanced ultrasound imaging agents as well as on-demand therapeutic agents for ischemic injuries based on the hypothesis that PVAX nanoparticles generate echogenic CO2 bubbles through H2O2-triggered oxidation of peroxalate esters and the merger of curcumin and PVAX exerts H2O2-activatable synergistic therapeutic actions. CUR-PVAX nanoparticles also displayed the drastic ultrasound signal in ischemic areas by generating CO2 bubbles. CUR-PVAX nanoparticles exhibited significantly higher antioxidant and anti-inflammatory activities than empty PVAX nanoparticles and equivalent curcumin in vascular endothelial cells. A mouse model of ischemic injury was used to evaluate the potential of CUR-PVAX nanoparticles as ultrasound imaging agents and on-demand therapeutic agents. CUR-PVAX nanoparticles significantly suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Moreover, CUR-PVAX nanoparticles significantly enhanced the level of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1, also known as CD31), leading to blood perfusion into ischemic tissues. We, therefore, believe that CUR-PVAX nanoparticles hold great translational potential as novel theranostic agents for ischemic diseases such as PAD.

Near infrared dye-conjugated oxidative stress amplifying polymer micelles for dual imaging and synergistic anticancer phototherapy.

The recent advances in nanotechnology have led to the development of smart nanomaterials that combine diagnostic and therapeutic functions and provide synergistic anticancer effects through the combination of different treatment modalities. Here, we report a promising theranostic nanoconstruct that can translate into multiple functionalities: fluorescence/photoacoustic imaging, acid-triggered generation of ROS (reactive oxygen species), heat and singlet oxygen production under near infrared (NIR) laser irradiation, and coupling oxidative anticancer therapy to dual imaging-guided photothermal/photodynamic therapy. An NIR dye-conjugated hydroxyl radical generating biodegradable polymer (HRGP-IR) is employed as a theranostic nanoplatform. HRGP-IR could self-assemble to form micelles and elevate oxidative stress by generating hydrogen peroxide and hydroxyl radical. Under the NIR (808 nm) laser irradiation, HRGP-IR micelles also generate heat and singlet oxygen to induce cancer cell death. In mouse xenograft models, HRGP-IR micelles accumulated in tumors preferentially and the tumor could be detected by dual imaging. Effective tumor ablation was achieved by HRGP-IR micelles (5 mg/kg) combined with NIR laser irradiation, demonstrating the synergistic anticancer effects of oxidative stress with photothermal heating. Given their dual imaging capability, anticancer phototherapy and highly potent synergistic anticancer activity with NIR laser irradiation, HRGP-IR micelles hold great potential as a nanotheranostic agent for cancer treatment.

Acid-triggered echogenic nanoparticles for contrast-enhanced ultrasound imaging and therapy of acute liver failure.

There has been increasing interest in the development of pathological stimulus-activatable nanoplatforms with theranostic functions. Here, we report ketalized maltodextrin (KMD) nanoparticles which are able to deliver therapeutic and imaging functions to the acidic conditions simultaneously, as may be found in the site of inflammation. KMD was synthesized as a platform of the theranostic nanoparticles by conjugating acid-cleavable hydrophobic moieties to maltodextrin through carbonate bonds. KMD nanoparticles could undergo acid-triggered hydrolytic degradation to generate carbon dioxide (CO2) bubbles, amplifying the ultrasound signal. The potential of KMD nanoparticles as a drug carrier was evaluated using silymarin as a model drug. KMD nanoparticles displayed significantly enhanced ultrasound contrast at acidic pH and released drug payloads in acid-triggered manners. The translational potential of silymarin-loaded KMD (s-KMD) nanoparticles as ultrasound contrast agents and therapeutic agents was thoroughly evaluated using cell culture models and mouse models of acetaminophen (APAP)-induced acute liver failure. s-KMD nanoparticles exhibited significantly enhanced ultrasound contrast in the APAP-intoxicated liver and also remarkably suppressed the hepatic damages by inhibiting the expression of pro-inflammatory cytokines. These results suggest that KMD nanoparticles hold tremendous potential as theranostic agents for various inflammatory diseases.

Molecularly Engineered Theranostic Nanoparticles for Thrombosed Vessels: H2O2-Activatable Contrast-Enhanced Photoacoustic Imaging and Antithrombotic Therapy.

A thrombus (blood clot), composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and an elevated level of hydrogen peroxide (H2O2), we developed thrombus-specific theranostic (T-FBM) nanoparticles that could provide H2O2-triggered photoacoustic signal amplification and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by H2O2 to generate CO2 bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a H2O2-triggered manner. T-FBM nanoparticles also exerted H2O2-activatable antioxidant, anti-inflammatory, and antiplatelet activities on endothelial cells. In mouse models of carotid arterial injury, T-FBM nanoparticles significantly enhanced the photoacoustic contrast specifically in thrombosed vessels and significantly suppressed thrombus formation. We anticipate that T-FBM nanoparticles hold great translational potential as nanotheranostics for H2O2-associated cardiovascular diseases.

Fibrin-Targeted and H2O2-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels.

A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nanomedicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (H2O2), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis. FTIAN inhibited the generation of H2O2 and suppressed the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) in activated platelets, demonstrating its intrinsic antioxidant, anti-inflammatory, and antiplatelet activity. In a mouse model of ferric chloride (FeCl3)-induced carotid thrombosis, FTIAN specifically targeted the obstructive thrombus and significantly enhanced the fluorescence/photoacoustic signal. When loaded with the antiplatelet drug tirofiban, FTIAN remarkably suppressed thrombus formation. Given its thrombus-specific imaging along with excellent therapeutic activities, FTIAN offers tremendous translational potential as a nanotheranostic agent for obstructive thrombosis.

Anticancer activity of biologically synthesized silver and gold nanoparticles on mouse myoblast cancer cells and their toxicity against embryonic zebrafish.

The aim of this study was to evaluate the anticancer activity of bioinspired silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mouse myoblast cancer cells (C2C12). Both AgNPs and AuNPs were biologically synthesized using Spinacia oleracea Linn., aqueous leaves extract. UV-Vis. spectrophotometer, high resolution-transmission electron microscopy (HR-TEM), field emission-scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) studies supported the successful synthesis of AgNPs and AuNPs. Both these NPs have shown cytotoxicity against C2C12 cells even at very low concentration (5µg/mL). Acridine orange/Ethidium bromide (AO/EB) dual staining confirmed the apoptotic morphological features. The levels of caspase enzymes (caspase-3 and caspase-7) were significantly up-regulated in NPs treated myoblast cells than the plant extract. Furthermore, in zebrafish embryo toxicity study, AgNPs showed 100% mortality at 3µg/mL concentration while AuNPs exhibited the same at much higher concentration (300mg/mL). Taken together, these results provide a preliminary guidance for the development of biomaterials based drugs to fight against the fatal diseases for example cancer.

H2O2-triggered bubble generating antioxidant polymeric nanoparticles as ischemia/reperfusion targeted nanotheranostics.

Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) leads to oxidative stress, causing inflammation and cellular damages and death. H2O2 is one of the most stable and abundant ROS and H2O2-mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H2O2 could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress-associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H2O2-triggered CO2-generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO2 through H2O2-triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H2O2-responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H2O2-triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H2O2-associated diseases.

Enhancement of objects in photoacoustic tomography using selective filtering.

Here we developed a real-time photoacoustic tomography (PAT) imaging acquisition device based on the linear array transducer utilized on ultrasonic devices. Also, we produced a phantom including diverse contrast media and acquired PAT imaging as the light source wavelength was changing to see if the contrast media reacted. Indocyanine green showed the highest reaction around the 800-nm band, methylene blue demonstrated the same in the 750-nm band, and gold nanoparticle showed the same in the 700-nm band. However, in the case of superparamagnetic iron oxide, we observed not reaction within the wavelength bands used herein to obtain imaging. Moreover, we applied selective filtering to the acquired PAT imaging to remove noise from around and reinforce the object's area. Consequentially, we could see the object area in the imaging was effectively detected and the image noise was removed.

Real-time photoacoustic tomograpghy using linear array probe and detection of line structure using Hough transform.

A real-time photoacoustic tomography (PAT) system is developed using a linear array probe and phantom images are acquired with a pattern of line structure. Moreover, it is attempted to detect line structures from the acquired images by Hough transform. This effort leads to the measurement of a process of magenta passing through a tube and acquisition of images at a speed of about 2 frame/sec. Besides, it is confirmed that the Hough transform applied on the acquired PAT images has the detection rate of about 50% for delineating a line structure.

Removal of baseline wandering in ECG signal by improved detrending method.

The very first step to process electrocardiogram (ECG) signal is to eliminate baseline wandering interference that is usually caused by electrode-skin impedance mismatch, motion artifacts due to a patient's body moment or respiratory breathing. A new method is thus suggested to remove baseline wandering in ECG by improving the detrending method that was originally proposed for eliminating slow non-stationary trends from heart rate variability (HRV). In our proposed method, a global trend is estimated in terms of baseline wandering by merging the local trend based on an ECG segment that represents a part of the ECG signal. The experimental results show that the improved detrending method can efficiently resolve baseline wandering without distorting any morphological characteristic embedded in the ECG signal in no time delay manner.

Design of the computerized 3D endoscopic imaging system for delicate endoscopic surgery.

This paper describes a 3D endoscopic video system designed to improve visualization and enhance the ability of the surgeon to perform delicate endoscopic surgery. In a comparison of the polarized and conventional electric shutter-type stereo imaging systems, the former was found to be superior in terms of both accuracy and speed for suturing and for the loop pass test. Among the groups performing loop passing and suturing, there was no significant difference in the task performance between the 2D and 3D modes, however, suturing was performed 15% (p < 0.05) faster in 3D mode by both groups. The results of our experiments show that the proposed 3D endoscopic system has a sufficiently wide viewing angle and zone for multi-viewing.

Evaluation of Elbow Stretch Reflex Using a Portable Hand-driven Isokinetic System in Normal Adults.

OBJECTIVE: To evaluate normal healthy persons without spasticity to observe normal findings of the elbow stretch reflex using a newly developed, portable, hand-driven spasticity-measuring system. METHOD: Thirty normal persons without any disease involving the central or peripheral nervous system were enrolled in this study. The portable hand-driven isokinetic system is able to measure the joint angle, angular velocity, electromyographic (EMG) signals, and torque during elbow passive extension-flexion. One set of 10 passive elbow extension and flexion movements was performed for data acquisition at each angular velocity, including 60, 90, 120, 150 and 180 degrees per second (°/sec). Electromyographic data were collected from the biceps brachii and the triceps brachii. Torque data were collected from sensors around the wrist. RESULTS: We were able to detect EMG activity and torque in all subjects by using the new portable hand-driven isokinetic system. EMG activity and torque increased with incremental increase of angular velocities. The joint angle of maximal EMG activity according to different angular velocities did not show any significant difference (116°-127° in elbow extension and 37°-66° in elbow flexion). The joint angles of maximal torque according to different angular velocities were not significantly different either. CONCLUSION: Using the portable hand-driven isokinetic system on the elbows of normal subjects, we were able to obtain expected results. By considering our normal findings of the elbow stretch reflex using this system, we propose that the various aspects of spasticity-related data can be measured successfully.