Comparison Of Interactive Voice Response (Ivr) With Paper Administration Of Instruments To Assess Functional Status, Sexual Function, And Quality Of Life In Elderly Men, Rc Rosen, Aj Stephens-Shields, Gr Cunningham, D Cifelli, D Cella, Jt Farrar, E Barrett-Connor, Ce Lewis, M Pahor, X Hou, Pj Snyder

Faculty, Staff and Students Publications

PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men = 65 years at each of two clinical sites. In …

Ct-Based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring For Fracture Prediction In Metastatic Femoral Lesions, Ta Damron, A Nazarian, V Entezari, C Brown, W Grant, N Calderon, Et Al.

Faculty, Staff and Students Publications

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and …

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific, V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty, Staff and Students Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies, Ms Siehr, Jl Noebels

Faculty, Staff and Students Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review, A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Glial Contributions To Neural Function And Disease, Mn Rasband

Faculty, Staff and Students Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience, G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Binomial Regression With A Misclassified Covariate And Outcome, Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty, Staff and Students Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Effect Of Two-Year Caloric Restriction On Bone Metabolism And Bone Mineral Density In Non-Obese Younger Adults: A Randomized Clinical Trial, Dt Villareal, L Fontana, Sk Das, Et Al.

Faculty, Staff and Students Publications

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus …

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …

Duration Estimates Within A Modality Are Integrated Sub-Optimally, Ming Bo Cai, David M. Eagleman

Faculty, Staff and Students Publications

Perceived duration can be influenced by various properties of sensory stimuli. For example, visual stimuli of higher temporal frequency are perceived to last longer than those of lower temporal frequency. How does the brain form a representation of duration when each of two simultaneously presented stimuli influences perceived duration in different way? To answer this question, we investigated the perceived duration of a pair of dynamic visual stimuli of different temporal frequencies in comparison to that of a single visual stimulus of either low or high temporal frequency. We found that the duration representation of simultaneously occurring visual stimuli is …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations and Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Prevalence Of Learned Grapheme-Color Pairings In A Large Online Sample Of Synesthetes, Nathan Withhoft, Jonathan Winawer, David M. Eagleman

Faculty, Staff and Students Publications

In this paper we estimate the minimum prevalence of grapheme-color synesthetes with letter-color matches learned from an external stimulus, by analyzing a large sample of English-speaking grapheme-color synesthetes. We find that at least 6% (400/6588 participants) of the total sample learned many of their matches from a widely available colored letter toy. Among those born in the decade after the toy began to be manufactured, the proportion of synesthetes with learned letter-color pairings approaches 15% for some 5-year periods. Among those born 5 years or more before it was manufactured, none have colors learned from the toy. Analysis of the …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Effects Of Oxytocin On Human Aggression, Joseph L. Alcorn Iii

Dissertations and Theses (Open Access)

EFFECTS OF OXYTOCIN ON HUMAN AGGRESSION

Joseph Louis Alcorn III, B.S.

Advisory Professor: Scott D. Lane, Ph.D.

Human interaction is comprised of common, yet complex, behaviors and the outcomes of these social behaviors can beneficially or detrimentally impact individual and public health. One social behavior that can have profound detrimental outcomes is aggression. Aggression is a class of social behavior that is particularly prevalent in individuals with antisocial personality disorder (ASPD) and comorbid substance use disorder (SUD). Aggression in these individuals can manifest at maladaptive levels that place considerable burdens on public health and communities. Therefore, understanding the neurobehavioral underpinnings …

Change Detection In Rhesus Monkeys And Humans, Deepna T. Devkar, Deepna T. Devkar

Dissertations and Theses (Open Access)

Visual working memory (VWM) is the temporary retention of visual information and a key component of cognitive processing. The classical paradigm for studying VWM and its encoding limitations has been change detection. Early work focused on how many items could be stored in VWM, leading to the popular theory that humans could remember no more than 4±1 items. More recently, proposals have suggested that VWM is a noisy, continuous resource distributed across virtually all items in the visual field, resulting in diminished memory quality rather than limited quantity. This debate about the nature of VWM has predominantly been studied with …

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster, Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty, Staff and Students Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

Mechanisms Of Astrocyte Contribution To Bortezomib-Induced Peripheral Neuropathy, Caleb R. Robinson

Dissertations and Theses (Open Access)

Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma and other non-solid malignancies, alone or in combination with other chemotherapy drugs. Like other chemotherapeutic agents, bortezomib treatment is frequently accompanied by chemotherapy-induced peripheral neuropathy (CIPN) that may be dose-limiting, adversely affecting quality of life and prognosis. The mechanisms behind bortezomib-induced peripheral neuropathy (BIPN) and CIPN overall are largely unknown. Recent findings in other pain models have indicated substantial involvement of glial cells in chronic pain. Although injury models have shown activation of both astrocytes and microglia following insult, research in other CIPN models has shown astrocytic activation …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Effects Of Resting State On Perceptual Learning, Sarah Eagleman Ph.D.

Dissertations and Theses (Open Access)

Psychophysical experiments in humans have demonstrated that improvements in perceptual learning tasks occur following daytime rests. The neural correlates of how rest influences subsequent sensory processing during these tasks remain unclear. One possible neural mechanism that may underlie this behavioral improvement is reactivation. Previously evoked network activity reoccurs – reactivates - in the absence of further stimulation. Reactivation was initially discovered in the hippocampus but has now been found in several brain areas including cortex. This phenomenon has been implicated as a general mechanism by which neural networks learn and store sensory information. However, whether reactivation occurs in areas relevant …

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations and Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations and Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations and Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

Spatial Warping By Oriented Line Detectors Can Counteract Neural Delays, Don A. Vaughn, David M. Eagleman

Faculty, Staff and Students Publications

The slow speed of neural transmission necessitates that cortical visual information from dynamic scenes will lag reality. The "perceiving the present" (PTP) hypothesis suggests that the visual system can mitigate the effect of such delays by spatially warping scenes to look as they will in ~100 ms from now (Changizi, 2001). We here show that the Hering illusion, in which straight lines appear bowed, can be induced by a background of optic flow, consistent with the PTP hypothesis. However, importantly, the bowing direction is the same whether the flow is inward or outward. This suggests that if the warping is …

Network Dynamics Of Visual Naming, Christopher R. Conner

Dissertations and Theses (Open Access)

Recognition and naming of objects and actions are fundamental components of language. They involve several different systems working in coordination to accomplish a complex behavior. During visual naming, sensory and semantic processing are carried out by dedicated cortical substrates in the temporal and occipital lobes, while response selection and articulatory planning are handled by prefrontal cortex. Despite decades of research using lesion analysis, functional MRI and electro-encephalography, the precise dynamics involved remain unknown due to the inadequate spatio-temporal resolution of these methodologies. Of particular interest is the organization of semantic knowledge and the degree of serial and parallel organization of …

Behavioral Responses To Methylphenidate: Correlations With Neuronal Activity In The Caudate Nucleus, Catherine M. Claussen

Dissertations and Theses (Open Access)

Methylphenidate is currently a drug of abuse and readily prescribed to both adolescents and adults. Chronic methylphenidate (MPH) exposure results in an increase in DA in the motive circuit, including the caudate nucleus (CN), similar to other drugs of abuse. This study focuses on research aimed to elucidate if there are intrinsic underlying differences in the CN electrophysiological activity of animals exhibiting different chronic responses to the same dose of MPH. Behavioral and caudate nucleus (CN) neuronal activity following acute and chronic doses of MPH was assessed by simultaneously recording the behavioral and neuronal activity. The experimental protocol lasted for …

Trpv1 Channels Contribute To Behavioral Hypersensitivity And Spontaneous Activity In Nociceptors After Spinal Cord Injury, Zizhen Wu

Dissertations and Theses (Open Access)

A majority of persons who have sustained spinal cord injury (SCI) develop chronic pain. While most investigators have assumed that the critical mechanisms underlying neuropathic pain after SCI are restricted to the central nervous system (CNS), recent studies showed that contusive SCI results in a large increase in spontaneous activity in primary nociceptors, which is correlated significantly with mechanical allodynia and thermal hyperalgesia. Upregulation of ion channel transient receptor vanilloid 1 (TRPV1) has been observed in the dorsal horn of the spinal cord after SCI, and reduction of SCI-induced hyperalgesia by a TRPV1 antagonist has been claimed. However, the possibility …

Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar

Dissertations and Theses (Open Access)

Role of Neurogranin in the regulation of calcium binding to Calmodulin

Anuja Chandrasekar, B.S

Advisor: M. Neal Waxham, Ph.D

The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, …

The Functional Organization Of Synaptic Vesicle Pools In A Retinal Bipolar Neuron, Proleta Datta

Dissertations and Theses (Open Access)

Ribbon synapses are found in sensory systems and are characterized by ‘ribbon-like’ organelles that tether synaptic vesicles. The synaptic ribbons co-localize with sites of calcium entry and vesicle fusion, forming ribbon-style active zones. The ability of ribbon synapses to maintain rapid and sustained neurotransmission is critical for vision, hearing and balance. At retinal ribbon synapses, three vesicle pools have been proposed. A rapid pool of vesicles that are docked at the plasma membrane, and whose fusion is limited only by calcium entry, a releasable pool of ATP-primed vesicles whose size also correlates with the number of ribbon-tethered vesicles, and a …

Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout

Dissertations and Theses (Open Access)

Traumatic brain injury (TBI) often results in disruption of the blood brain barrier (BBB), which is an integral component to maintaining the central nervous system homeostasis. Recently cytosolic calcium levels ([Ca²⁺]i), observed to elevate following TBI, have been shown to influence endothelial barrier integrity. However, the mechanism by which TBI-induced calcium signaling alters the endothelial barrier remains unknown. In the present study, an in vitro BBB model was utilized to address this issue. Exposure of cells to biaxial mechanical stretch, in the range expected for TBI, resulted in a rapid cytosolic calcium increase. Modulation of intracellular and extracellular …