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Telestroke networks reduce disparities in acute stroke care between metropolitan primary stroke centers and remote hospitals. Current technologies used to conduct remote patient assessments have very high start-up costs, yet they cannot consistently establish quality connection in a timely manner. Smartphgones can be used for high quality video teleconferencing (HQ-VTC). They are relatively inexpensive and widley used among healthcare providers. We aimed to study the reliability of HQ-VTC using smartphones for conducting the NIHSS. Two vascular neurologists (VNs) assessed 83 stroke patients with the NIHSS. The remote VN assessed patients using videoconferencing on a smartphone with the assistance of a bedside medical aide. The bedside VN rated patients ontemporaneously. Each VN was blinded to the other's NIHSS scores. We tested the inter-method agreement and physician satisfaction with the device. We demonstrated high total NIHSS score correlation between the methods (r=0.941, p<0.001). The mean total NIHSS scores for bedside and remote assessments were 7.3 plus or minus 7.9 and 6.7 plus or minus 7.6 with ranges of 0-30 and 0-37, respectively. Seven NIHSS categories had significantly high agreement beyond chance: LOC-questions, LOC-commands, visual fields, motor left arm, motor right arm, motor left leg, motor right leg; seven categories had moderate agreement: LOC-consciousness, best gaze, facial palsy, sensory, best language, dysarthria, extinction/inattention; one category had poor agreement: ataxia. There was high physician satisfaction with the device. The VNs rated 96% of the assessments as good or very good for "image quality," "sound quality," "ease of use," and "ability to assess subject using NIHSS," and 84% of the assesssments as good or very good for "reception in hospital." The smartphones with HQ-VTC is reliable, easy to use, and affordable for telestroke NIHSS administration. This device has high physician satisfaction. With the variety of smartphones and professional medical applications available today, the telestroke practitioner has all the tools necessary for fast clinical decision-makingby accessing electronic medial records, viewing images, and tracking patient vitals.
ContributorsVegunta, Sravanthi (Author) / Demaerschalk, Bart (Thesis director) / Santello, Marco (Committee member) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Current research into live-cell dynamics, particularly those relating to chromatin structure and remodeling, are limited. The tools that are used to detect state changes in chromatin, such as Chromatin Immunoprecipitation and qPCR, require that the cell be killed off. This limits the ability of researchers to pinpoint changes in live cells over a longer period of time. As such, there is a need for a live-cell sensor that can detect chromatin state changes. The Chromometer is a transgenic chromatin state sensor designed to better understand human cell fate and the chromatin changes that occur. HOXD11.12, a DNA sequence that attracts repressive Polycomb group (PCG) proteins, was placed upstream of a core promoter-driven fluorescent reporter (AmCyan fluorescent protein, CFP) to link chromatin repression to a CFP signal. The transgene was stably inserted at an ectopic site in U2-OS (osteosarcoma) cells. Expression of CFP should reflect the epigenetic state at the HOXD locus, where several genes are regulated by Polycomb to control cell differentiation. U2-OS cells were transfected with the transgene and grown under selective pressure. Twelve colonies were identified as having integrated parts from the transgene into their genomes. PCR testing verified 2 cell lines that contain the complete transgene. Flow cytometry indicated mono-modal and bimodal populations in all transgenic cell colonies. Further research must be done to determine the effectiveness of this device as a sensor for live cell state change detection.
ContributorsBarclay, David (Co-author) / Simper, Jan (Co-author) / Haynes, Karmella (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The purpose of this paper was to systematically review current literature regarding the effect of hand splints on aesthetic outcomes for individuals with acquired hand deformities. Hand splints vary in form and function, and are used to maintain or ameliorate hand function and aesthetics. A literature search was performed on peer-reviewed publications that used splinting as an intervention for conservative hand improvement. Evidence from ten randomized clinical trials (published from 2003 to 2015) was evaluated for aesthetic improvement among a total of 659 subjects. Cosmetic outcomes were analyzed by a change in angle measurements, such as extensor lag, ulnar deviation, and passive and active range of motion. Of these ten studies, five focused on hand deformities caused by neurological impairment, while the other five measured those with musculoskeletal complications. Only two of the ten studies concluded that splinting could aesthetically improve the hands, and only one of these reporting statistical significance in its data. The data was not only limited in quantity, but was presented in heterogeneous formats. There was an extensive variation in measured outcomes, intervention protocols, follow-up times, and many other aspects of the studies; this dissimilarity led to difficulty in performing a systematic assessment. The majority of evidence concludes that splinting does not improve the appearance of deformities, however none directly investigated this measure. Therefore, further RCTs that include measurements of cosmetic traits are necessary to better quantify the effect of splinting for management of hand deformities. This review was the first of its kind to evaluate the correction of hand deformities using splints as an intervention.
ContributorsVale, Nicholas Marshall (Author) / Santello, Marco (Thesis director) / Skiba, Jeffry (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor, Contributor) / School of Biological and Health Systems Engineering (Contributor)
Created2017-05
Description
Skin wounds can be caused by traumatic lacerations or incisions which disrupt the structural and functional integrity of the skin. Wound closure and primary intention treatment of the wound as soon as possible is crucial to avoid or minimize the risk of infection that can result in a compromised healing rate or advanced functional intricacy. The gold standard treatment for skin wound healing is suturing. Light-activated tissue sealing is an appealing alternative to sutures as it seals the wound edges minimizing the risk of infection and scarring, especially when utilized along with biodegradable polymeric biomaterials in the wound bed. Silk fibroins can be used as a biodegradable biomaterial that possesses properties supporting cell migration and proliferation in the tissue it interacts with. In addition, histamine treatment is shown to have extensive effects on cellular functions promoting wound healing. Here, the evaluation of Laser-activated Sealants (LASE) consisting of silk fibroin films induced with Indocyanine Green dye in a wound sealed with laser in the presence of Histamine receptor agonists H1R, H2R and H4R take place. The results were evaluated using Trans-epidermal Water Loss (TEWL), histological and analytical techniques where immune cell biomarkers Arginase-1, Ly6G, iNOS, Alpha-SMA, Proliferating Cell Nuclear Antigen (PCNA), and E-Cadherin were used to study the activity of specific cells such as macrophages, neutrophils, and myofibroblasts that aid in wound healing. PBS was used as a control for histamine receptor agonists. It was found that TEWL increased when treated with H1 receptor agonists while decreasing significantly in H2R and H4R-treated wounds. Arginase-1 activity improved, while it displayed an inverse relationship compared to iNOS. H4R agonist escalated Alpha-SMA cells, while others did not have any significant difference. Ly6G activity depleted in all histamine agonists significantly, while PCNA and E-Cadherin failed to show a positive or negative effect.
ContributorsPatel, Dirghau Manishbhai (Author) / Rege, Kaushal (Thesis advisor) / Massia, Stephen (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2022
Description
The advent of CRISPR/Cas9 revolutionized the field of genetic engineering and gave rise to the development of new gene editing tools including prime editing. Prime editing is a versatile gene editing method that mediates precise insertions and deletions and can perform all 12 types of point mutations. In turn, prime editing represents great promise in the design of new gene therapies and disease models where editing was previously not possible using current gene editing techniques. Despite advancements in genome modification technologies, parallel enrichment strategies of edited cells remain lagging behind in development. To this end, this project aimed to enhance prime editing using transient reporter for editing enrichment (TREE) technology to develop a method for the rapid generation of clonal isogenic cell lines for disease modeling. TREE uses an engineered BFP variant that upon a C-to-T conversion will convert to GFP after target modification. Using flow cytometry, this BFP-to-GFP conversion assay enables the isolation of edited cell populations via a fluorescent reporter of editing. Prime induced nucleotide engineering using a transient reporter for editing enrichment (PINE-TREE), pairs prime editing with TREE technology to efficiently enrich for prime edited cells. This investigation revealed PINE-TREE as an efficient editing and enrichment method compared to a conventional reporter of transfection (RoT) enrichment strategy. Here, PINE-TREE exhibited a significant increase in editing efficiencies of single nucleotide conversions, small insertions, and small deletions in multiple human cell types. Additionally, PINE-TREE demonstrated improved clonal cell editing efficiency in human induced pluripotent stem cells (hiPSCs). Most notably, PINE-TREE efficiently generated clonal isogenic hiPSCs harboring a mutation in the APOE gene for in vitro modeling of Alzheimer’s Disease. Collectively, results gathered from this study exhibited PINE-TREE as a valuable new tool in genetic engineering to accelerate the generation of clonal isogenic cell lines for applications in developmental biology, disease modeling, and drug screening.
ContributorsKostes, William Warner (Author) / Brafman, David (Thesis advisor) / Jacobs, Bertram (Committee member) / Lapinaite, Audrone (Committee member) / Tian, Xiaojun (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2022
Description
Although previous studies have elucidated the role of position feedback in the regulation of movement, the specific contribution of Golgi tendon organs (GTO) in force feedback, especially in stabilizing voluntary limb movements, has remained theoretical due to limitations in experimental techniques. This study aims to establish force feedback regulation mediated by GTO afferent signals in two phases. The first phase of this study consisted of simulations using a neuromusculoskeletal model of the monoarticular elbow flexor (MEF) muscle group, assess the impact of force feedback in maintaining steady state interaction forces against variable environmental stiffness. Three models were trained to accurately reach an interaction force of 40N, 50N and 60N respectively, using a fixed stiffness level. Next, the environment stiffness was switched between untrained levels for open loop (OL) and closed loop (CL) variants of the same model. Results showed that compared to OL, CL showed decreased force deviations by 10.43%, 12.11% and 13.02% for each of the models. Most importantly, it is also observed that in the absence of force feedback, environment stiffness is found to have an effect on the interaction force. In the second phase, human subjects were engaged in experiments utilizing an instrumented elbow exoskeleton that applied loads to the MEF muscle group, closely mimicking the simulation conditions. The experiments consisted of reference, blind and catch trial types, and 3 stiffness levels. Subjects were first trained to reach for a predetermined target force. During catch trials, stiffness levels were randomized between reaches. Responses obtained from these experiments showed that subjects were able to regulate forces with no significant effects of trial type or stiffness level. Since experimental results align closely with that of closed loop model simulations, the presence of force feedback mechanisms mediated by GTO within the human neuromuscular system is established. This study not only unveils the critical involvement of GTO in force feedback but also emphasizes the importance of understanding these mechanisms for developing advanced neuroprosthetics and rehabilitation strategies, shedding light on the intricate interplay between sensory inputs and motor responses in human proprioception.
ContributorsAbishek, Kevin (Author) / Lee, Hyunglae (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2023
Description
A current thrust in neurorehabilitation research involves exogenous neuromodulation of peripheral nerves to enhance neuroplasticity and maximize recovery of function. This dissertation presents the results of four experiments aimed at assessing the effects of trigeminal nerve stimulation (TNS) and occipital nerve stimulation (ONS) on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Aim 1a, the effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three participants (22.75±4.6 y/o), performed a visuomotor rotation task and received TNS before encountering rotation of hand visual feedback. In Aim 1b, TNS at 3 kHz, which has been shown to be more tolerable at higher current intensities, was evaluated in 42 additional subjects (23.4±4.6 y/o). Results indicated that 3 kHz stimulation accelerated learning while 60 Hz stimulation slowed learning, suggesting a frequency-dependent effect on learning. In Aim 2, the effect of online TNS using 120 and 60 Hz were characterized to determine if this protocol would deliver better outcomes. Sixty-three participants (23.2±3.9 y/o) received either TNS or sham concurrently with perturbed visual feedback. Results showed no significant differences among groups. However, a cross-study comparison of results obtained with 60 Hz offline TNS showed a statistically significant improvement in learning rates with online stimulation relative to offline, suggesting a timing-dependent effect on learning. In Aim 3, TNS and ONS were compared using the best protocol from previous aims (offline 3 kHz). Additionally, concurrent stimulation of both nerves was explored to look for potential synergistic effects. Eighty-four participants (22.9±3.2 y/o) were assigned to one of four groups: TNS, ONS, TNS+ONS, and sham. Visual inspection of learning curves revealed that the ONS group demonstrated the fastest learning among groups. However, statistical analyses did not confirm this observation. In addition, the TNS+ONS group appeared to learn faster than the sham and TNS groups but slower than the ONS only group, suggesting no synergistic effects using this protocol, as initially hypothesized.
The results provide new information on the potential use of TNS and ONS in neurorehabilitation and performance enhancement in the motor domain.
ContributorsArias, Diego (Author) / Buneo, Christopher (Thesis advisor) / Schaefer, Sydney (Committee member) / Helms-Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2023
Description
Multisensory integration is the process by which information from different sensory modalities is integrated by the nervous system. This process is important not only from a basic science perspective but also for translational reasons, e.g., for the development of closed-loop neural prosthetic systems. A mixed virtual reality platform was developed to study the neural mechanisms of multisensory integration for the upper limb during motor planning. The platform allows for selection of different arms and manipulation of the locations of physical and virtual target cues in the environment. The system was tested with two non-human primates (NHP) trained to reach to multiple virtual targets. Arm kinematic data as well as neural spiking data from primary motor (M1) and dorsal premotor cortex (PMd) were collected. The task involved manipulating visual information about initial arm position by rendering the virtual avatar arm in either its actual position (veridical (V) condition) or in a different shifted (e.g., small vs large shifts) position (perturbed (P) condition) prior to movement. Tactile feedback was modulated in blocks by placing or removing the physical start cue on the table (tactile (T), and no-tactile (NT) conditions, respectively). Behaviorally, errors in initial movement direction were larger when the physical start cue was absent. Slightly larger directional errors were found in the P condition compared to the V condition for some movement directions. Both effects were consistent with the idea that erroneous or reduced information about initial hand location led to movement direction-dependent reach planning errors. Neural correlates of these behavioral effects were probed using population decoding techniques. For small shifts in the visual position of the arm, no differences in decoding accuracy between the T and NT conditions were observed in either M1 or PMd. However, for larger visual shifts, decoding accuracy decreased in the NT condition, but only in PMd. Thus, activity in PMd, but not M1, may reflect the uncertainty in reach planning that results when sensory cues regarding initial hand position are erroneous or absent.
ContributorsPhataraphruk, Preyaporn Kris (Author) / Buneo, Christopher A (Thesis advisor) / Zhou, Yi (Committee member) / Helms Tillery, Steve (Committee member) / Greger, Bradley (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2023
Description
With an aging population, the number of later in life health related incidents like stroke stand to become more prevalent. Unfortunately, the majority those who are most at risk for debilitating heath episodes are either uninsured or under insured when it comes to long term physical/occupational therapy. As insurance companies lower coverage and/or raise prices of plans with sufficient coverage, it can be expected that the proportion of uninsured/under insured to fully insured people will rise. To address this, lower cost alternative methods of treatment must be developed so people can obtain the treated required for a sufficient recovery. The presented robotic glove employs low cost fabric soft pneumatic actuators which use a closed loop feedback controller based on readings from embedded soft sensors. This provides the device with proprioceptive abilities for the dynamic control of each independent actuator. Force and fatigue tests were performed to determine the viability of the actuator design. A Box and Block test along with a motion capture study was completed to study the performance of the device. This paper presents the design and classification of a soft robotic glove with a feedback controller as a at-home stroke rehabilitation device.
ContributorsAxman, Reed C (Author) / Zhang, Wenlong (Thesis advisor) / Santello, Marco (Committee member) / McDaniel, Troy (Committee member) / Arizona State University (Publisher)
Created2022
Description
Ecology has been an actively studied topic recently, along with the rapid development of human microbiota-based technology. Scientists have made remarkable progress using bioinformatics tools to identify species and analyze composition. However, a thorough understanding of interspecies interactions of microbial ecosystems is still lacking, which has been a significant obstacle in the further development of related technologies. In this work, a genetic circuit design principle with synthetic biology approaches is developed to form two-strain microbial consortia with different inter-strain interactions. The microbial systems are well-defined and inducible. Co-culture experiment results show that our microbial consortia behave consistently with previous ecological knowledge and thus serves as excellent model systems to simulate ecosystems with similar interactions. Colony patterns also emerge when co-culturing multiple species on solid media. With the engineered microbial consortia, image-processing based methods were developed to quantify the shape of co-culture colonies and distinguish microbial consortia with different interactions. Factors that affect the population ratios were identified through induction and variations in the inoculation process. Further time-lapse experiments revealed the basic rules of colony growth, composition variation, patterning, and how spatial factors impact the co-culture colony.
ContributorsChen, Xingwen (Author) / Wang, Xiao (Thesis advisor) / Kuang, Yang (Committee member) / Tian, Xiaojun (Committee member) / Brafman, David (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2022