Medicine and Health Sciences Commons^™

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …

The Climate Of Neurofeedback: Scientific Rigour And The Perils Of Ideology, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

Over the last six decades, an in-group with ideological and financial stakes has been conducting sub-par research to develop an ostensibly effective clinical intervention: EEG-neurofeedback. More recently, however, a string of independent studies featuring increased scientific rigour and tighter experimental controls has challenged the foundation on which EEG-neurofeedback stands. Earlier this year, Brain published one of the most robust EEG-neurofeedback experiments to date (Schabus et al., 2017), which sparked a flurry of correspondence concerning the therapeutic value of neurofeedback (Fovet et al., 2017; Schabus, 2017); notably, a parallel discussion continues in Lancet Psychiatry …

Combinational Sirna Delivery Using Hyaluronic Acid Modified Amphiphilic Polyplexes Against Cell Cycle And Phosphatase Proteins To Inhibit Growth And Migration Of Triple-Negative Breast Cancer Cells, Manoj B. Parmar, Daniel Nisakar Meenakshi Sundaram, Remant Bahadur Kc, Robert Maranchuk, Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludağ

Pharmacy Faculty Articles and Research

Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored PEI/HA formulation suggested better interaction of complexes with breast cancer cells due to …

Cortical Contribution To Linear, Non-Linear And Frequency Components Of Motor Variability Control During Standing, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Motor variability is an inherent feature of all human movements and reflects the quality of functional task performance. Depending on the requirements of the motor task, the human sensory-motor system is thought to be able to flexibly govern the appropriate level of variability. However, it remains unclear which neurophysiological structures are responsible for the control of motor variability. In this study, we tested the contribution of cortical cognitive resources on the control of motor variability (in this case postural sway) using a dual-task paradigm and furthermore observed potential changes in control strategy by evaluating Ia-afferent integration (H-reflex). Twenty healthy subjects …

Volition And Action In The Human Brain: Processes, Pathologies, And Reasons, Itzhak Fried, Patrick Haggard, Biyu J. He, Aaron Schurger

Psychology Faculty Articles and Research

Humans seem to decide for themselves what to do, and when to do it. This distinctive capacity may emerge from an ability, shared with other animals, to make decisions for action that are related to future goals, or at least free from the constraints of immediate environmental inputs. Studying such volitional acts proves a major challenge for neuroscience. This review highlights key mechanisms in the generation of voluntary, as opposed to stimulus-driven actions, and highlights three issues. The first part focuses on the apparent spontaneity of voluntary action. The second part focuses on one of the most distinctive, but elusive, …

Theta-Burst Microstimulation In The Human Entorhinal Area Improves Memory Specificity, Ali S. Titiz, Michael R. H. Hill, Emily A. Mankin, Zahra M. Aghajan, Dawn Eliashiv, Natalia Tchemodanov, Uri Maoz, John Stern, Michelle E. Tran, Peter Schuette, Eric Behnke, Nanthia A. Suthana, Itzhak Fried

Psychology Faculty Articles and Research

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants …

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …

The Psychology Of Neurofeedback: Clinical Intervention Even If Applied Placebo, Robert T. Thibault, Amir Raz

Psychology Faculty Articles and Research

Advocates of neurofeedback make bold claims concerning brain regulation, treatment of disorders, and mental health. Decades of research and thousands of peer-reviewed publications support neurofeedback using electroencephalography (EEG-nf); yet, few experiments isolate the act of receiving feedback from a specific brain signal as a necessary precursor to obtain the purported benefits. Moreover, while psychosocial parameters including participant motivation and expectation, rather than neurobiological substrates, seem to fuel clinical improvement across a wide range of disorders, for-profit clinics continue to sprout across North America and Europe. Here, we highlight the tenuous evidence supporting EEG-nf and sketch out the weaknesses of this …

Precursor Processes Of Human Self-Initiated Action, Nima Khalighinejad, Aaron Schurger, Andrea Desantis, Leor Zmigrod

Psychology Faculty Articles and Research

A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such “readiness potentials” (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous ‘skip’ responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial …

Efficacy And Safety Comparison Between Suberoylanilide Hydroxamic Acid And Mitomycin C In Reducing The Risk Of Corneal Haze After Prk Treatment In Vivo, Govindaraj Anumanthan, Ajay Sharma, Michael R. Waggoner, Chuck W. Hamm, Suneel Gupta, Nathan P. Hesemann, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE:

This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo.

METHODS:

Corneal haze in rabbits was produced with −9.00 diopter PRK. A single application of SAHA (25 μM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence.

RESULTS:

Single topical adjunct use of SAHA (25 μM) or MMC (0.02%) after PRK attenuated more than 95% corneal …

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Pharmacy Faculty Articles and Research

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …

Trkb-Enhancer Facilitates Functional Recovery After Traumatic Brain Injury, John Marshall, Joanna Szmydynger-Chodobska, Mengia S. Rioult-Pedotti, Kara Lau, Andrea T. Chin, Siva K. Reddy Kotla, Rakesh Tiwari, Keykavous Parang, Steven W. Threlkeld, Adam Chodobski

Pharmacy Faculty Articles and Research

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the …

De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan

Pharmacy Faculty Articles and Research

The thyroid gland secretes primarily tetraiodothyronine (T₄), and some triiodothyronine (T₃). Under normal physiological circumstances, only one-fifth of circulating T₃ is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T₃ toxicosis. Thyroidal T₄ production results from iodination of thyroglobulin (TG) at residues Tyr⁵ and Tyr¹³⁰, whereas thyroidal T₃ production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T₃ is formed …

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

My Crown And Glory: Community, Identity, Culture, And Black Women’S Concerns Of Hair Product-Related Breast Cancer Risk, Dede K. Teteh, Susanne B. Montgomery, Sabine Monice, Laura Stiel, Phyllis Y. Clark, Eudora Mitchell

Health Sciences and Kinesiology Faculty Articles

Breast cancer (BC) incidence rates for Black and non-Hispanic White women have recently converged; however, Black women continue to die at higher rates from the disease. Black women also use hair products containing hormonally active chemicals at higher rates than other races and ethnic groups. Studies now link chemical components in hair and personal care products to breast cancer risk. Using a community-based participatory research approach, this qualitative study explored community concerns about the role of hair products on breast cancer risk. Focus groups and key informant interviews using triangulation to assure relevant perspectives (women with and without breast cancer …

Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari

Pharmacy Faculty Articles and Research

CN2097 (R₇Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR₇ and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR₇) …

The Motor Cortical Representation Of A Muscle Is Not Homogeneous In Brain Connectivity, Jo Armour Smith, Alaa Albishi, Sarine Babikian, Skulpan Asavasopon, Beth E. Fisher, Jason Kutch

Physical Therapy Faculty Articles and Research

Functional connectivity patterns of the motor cortical representational area of single muscles have not been extensively mapped in humans, particularly for the axial musculature. Functional connectivity may provide a neural substrate for adaptation of muscle activity in axial muscles that have both voluntary and postural functions. The purpose of this study was to combine brain stimulation and neuroimaging to both map the cortical representation of the external oblique (EO) in primary motor cortex (M1) and supplementary motor area (SMA), and to establish the resting-state functional connectivity associated with this representation. Motor evoked potentials were elicited from the EO muscle in …

Bendablesound: An Elastic Multisensory Surface Using Touch-Based Interactions To Assist Children With Severe Autism During Music Therapy, Franceli L. Cibrian, Oscar Peña, Deysi Ortega, Monica Tentori

Engineering Faculty Articles and Research

Neurological Music Therapy uses live music to improve the sensorimotor regulation of children with severe autism. However, they often lack musical training and their impairments limit their interactions with musical instruments. In this paper, we present our co-design work that led to the BendableSound prototype: an elastic multisensory surface encouraging users to practice coordination movements when touching a fabric to play sounds. We present the results of a formative study conducted with 18 teachers showing BendableSound was perceived as “usable” and “attractive”. Then, we present a deployment study with 24 children with severe autism showing BendableSound is “easy to use” …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Patient Activation Among Diverse Populations: A Systematic Review, Megan Kenney

Student Scholar Symposium Abstracts and Posters

The purpose of this article was to review the current research regarding patient activation among diverse populations. Patient activation is defined as an individual’s knowledge, skill, and confidence in managing his or her own health and health care. A total of 62 articles were used in this review (54 primary research articles, six retrospective analyses, and two systematic reviews). Articles were obtained using the EBSCO search engine through the Leatherby Libraries at Chapman University. Preliminary and secondary searches were conducted using the keywords “patient activation.” Only articles published within the last ten years (2007 to 2017) were included to ensure …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

Role Of Corpus Callosum Integrity In Arm Function Differs Based On Motor Severity After Stroke, Jill Campbell Stewart, Pritha Dewanjee, George Tran, Erin Burke Quinlan, Lucy Dodakian, Alison Mckenzie, Jill See, Steven C. Cramer

Physical Therapy Faculty Articles and Research

While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from …

What Is The Contribution Of Ia-Afference For Regulating Motor Output Variability During Standing?, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Motor variability is an inherent feature of all human movements, and describes the system‘s stability and rigidity during the performance of functional motor tasks such as balancing. In order to ensure successful task execution, the nervous system is thought to be able to flexibly select the appropriate level of variability. However, it remains unknown which neurophysiological pathways are utilized for the control of motor output variability. In responding to natural variability (in this example sway), it is plausible that the neuro-physiological response to muscular elongation contributes to restoring a balanced upright posture. In this study, the postural sway of 18 …

Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi

Library Articles and Research

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Actionable Patient Safety Solution (Apss) #3d: Pediatric Adverse Drug Events, Ron Jordan, Jerika Lam, Nathaniel Sims, Anne Lyren, Coco Yang

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce the incidence of pediatric adverse drug events (pADEs) and harm ... [that] combine[s] leadership strategies, software (healthcare IT), hardware (drug compounding systems, drug delivery technology, and physiological monitoring systems), and most importantly people (changes in clinical practice, protocols and education)" to protect pediatric patients.

Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce errors in the recognition and treatment of [severe hypoglycemia]".