Medical Specialties Commons^™

Use Of Video Alone For Differentiation Of Epileptic Seizures From Non-Epileptic Spells: A Systematic Review And Meta-Analysis, Cemal Karakas, Liam D Ferreira, Zulfi Haneef

Faculty, Staff and Students Publications

Introduction: Review of videos (without electroencephalography) to differentiate epileptic seizures (ES) from non-epileptic spells (NES) may be helpful where epilepsy monitoring is not feasible. Previous studies of video-based diagnosis have suffered from variable accuracy, sensitivity, and specificity.

Methods: We systematically reviewed relevant literature in PubMed, Embase, and Web of Science from inception to September 2022, identifying articles that reported on the video-based diagnosis of ES and NES. In primary analysis, for each study, the most expert group was chosen when different groups of reviewers classified the videos (e.g., epilepsy specialists and general neurologists). In secondary analysis, we compared the diagnostic …

Robotic Surgery And Hospital Reimbursement, Nicholas H Yim, Jacob Mccarter, Tareck Haykal, Ali M Aral, Jessie Z Yu, Edward Reece, Sebastian Winocour

Faculty, Staff and Students Publications

The field of plastic surgery remains at the forefront of technological and surgical innovation. However, the promising applications of robotics in plastic surgery must be thoughtfully balanced with hospital finances and reimbursements. Robotic systems have been studied extensively across multiple surgical disciplines and across diverse health care systems. The results show that there may be equal or better patient outcomes than alternatives. In an era where fiscal responsibility in health care is a top priority, thoughtful budgeting and spending must be considered and revisited frequently to attain sustainable organizational models that ensure appropriate use of robotic technology.

Exploring Gastrointestinal Health In Mecp2 Duplication Syndrome, Davut Pehlivan, Muharrem Ak, Daniel G Glaze, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare neurogenetic syndrome caused by duplications of MECP2 at the Xq28 region. Although constipation and gastrointestinal reflux are reported in MDS, a comprehensive characterization of gastrointestinal health has not been fully explored.

METHODS: We conducted a parent survey to explore the characteristics of gastrointestinal health in individuals with MDS using a secure online registry and compared differences in gastrointestinal symptoms between individuals with MDS and those with Rett syndrome (RTT).

KEY RESULTS: One hundred six surveys were analyzed. Symptoms commonly associated with constipation occurred in 72% to 89% of MDS individuals. Eleven percent …

Isolated Cervical Dystonia: Diagnosis And Classification, Alberto Albanese, Kailash P Bhatia, Francisco Cardoso, Cynthia Comella, Giovanni Defazio, Victor S C Fung, Mark Hallett, Joseph Jankovic, Hyder A Jinnah, Ryuji Kaji, Joachim K Krauss, Anthony Lang, Eng King Tan, Marina A J Tijssen, Marie Vidailhet

Faculty, Staff and Students Publications

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to …

Sculpting Astrocyte Diversity Through Circuits And Transcription, Yi-Ting Cheng, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the …

Automated Capture And Analysis Of Circulating Tumor Cells In Pediatric, Adolescent And Young Adult Patients With Central Nervous System Tumors, Wafik Zaky, Dristhi Ragoonanan, Izhar Batth, Long Dao, Jian Wang, Xueqing Xia, Najat C Daw, Jonathan B Gill, Soumen Khatua, Shulin Li

Faculty, Staff and Student Publications

Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral …

C9orf72 Poly(Pr) Mediated Neurodegeneration Is Associated With Nucleolar Stress, M. E. Cicardi, J. H. Hallgren, D. Mawrie, K. Krishnamurthy, S. S. Markandaiah, A. T. Nelson, V. Kankate, E. N. Anderson, P. Pasinelli, U. B. Pandey, C. M. Eischen, D. Trotti

Farber Institute for Neuroscience Faculty Papers

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is aberrantly translated in the sense and antisense directions into dipeptide repeat proteins, among which poly proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when heterologously expressed in neurons and other cell types. We show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR strongly accumulates in the nucleolus, a nuclear structure critical in regulating the cell stress response. We determined that, in neurons, PR caused nucleolar stress and increased levels of the transcription factor p53. …

Genetics Of Functional Seizures; A Scoping Systematic Review, Ali A. Asadi-Pooya, Mark Hallett, Nafiseh Mirzaei Damabi, Khatereh Fazelian Dehkordi

Department of Neurology Faculty Papers

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field.

Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing.

Results: We identified three original studies. …

Age-Related Decline In Hippocampal Tyrosine Phosphatase Ptpro Is A Mechanistic Factor In Chemotherapy-Related Cognitive Impairment., Zhimeng Yao, Hongmei Dong, Jianlin Zhu, Liang Du, Yichen Luo, Qing Liu, Shixin Liu, Yusheng Lin, Lu Wang, Shuhong Wang, Wei Wei, Keke Zhang, Qingjun Huang, Xiaojun Yu, Weijiang Zhao, Haiyun Xu, Xiaofu Qiu, Yunlong Pan, Xingxu Huang, Sai-Ching Jim Yeung, Dianzheng Zhang, Hao Zhang

PCOM Scholarly Works

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are …

Correlative Cryo-Fib And Cryo-Et Of Dendritic Spines And Synaptic Connections, Erik D Anderson, Christopher A Cronkite, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

No abstract provided.

Clinical And Functional Correlates Of Parkinsonism In A Population-Based Sample Of Individuals Aged 75 +: The Pietà Study, Thiago Cardoso Vale, Francisco Eduardo Costa Cardoso, Danilo Jorge Da Silva, Elisa De Paula Franca Resende, Débora Palma Maia, Mauro César Quintão Cunningham, Henrique Cerqueira Guimarães, João Carlos Barbosa Machado, Antônio Lúcio Teixeira, Paulo Caramelli, Maira Tonidandel Barbosa

Faculty, Staff and Student Publications

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG].

METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG …

Single-Cell Chromatin Accessibility Profiling Of Acute Myeloid Leukemia Reveals Heterogeneous Lineage Composition Upon Therapy-Resistance, Huihui Fan, Feng Wang, Andy Zeng, Alex Murison, Katarzyna Tomczak, Dapeng Hao, Fatima Zahra Jelloul, Bofei Wang, Praveen Barrodia, Shaoheng Liang, Ken Chen, Linghua Wang, Zhongming Zhao, Kunal Rai, Abhinav K Jain, John Dick, Naval Daver, Andy Futreal, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of therapy resistance. Since the cell of origin can impact response to therapy, it is crucial to understand the lineage composition of AML cells at time of therapy resistance. Here we leverage single-cell chromatin accessibility profiling of 22 AML bone marrow aspirates from eight patients at time of therapy resistance and following subsequent therapy to characterize their lineage landscape. Our findings reveal a complex lineage architecture of therapy-resistant AML cells that are primed for stem and progenitor lineages and spanning quiescent, activated and late stem cell/progenitor states. Remarkably, …

Memory Rescue And Learning In Synaptic Impaired Neuronal Circuits, Kwan Tung Li, Daoyun Ji, Changsong Zhou

Faculty, Staff and Students Publications

Neuronal impairment is a characteristic of Alzheimer's disease (AD), but its effect on neural activity dynamics underlying memory deficits is unclear. Here, we studied the effects of synaptic impairment on neural activities associated with memory recall, memory rescue, and learning a new memory, in an integrate-and-fire neuronal network. Our results showed that reducing connectivity decreases the neuronal synchronization of memory neurons and impairs memory recall performance. Although, slow-gamma stimulation rescued memory recall and slow-gamma oscillations, the rescue caused a side effect of activating mixed memories. During the learning of a new memory, reducing connectivity caused impairment in storing the new …

Genome-Wide Identification And Phenotypic Characterization Of Seizure-Associated Copy Number Variations In 741,075 Individuals, Ludovica Montanucci, David Lewis-Smith, Ryan L Collins, Lisa-Marie Niestroj, Shridhar Parthasarathy, Julie Xian, Shiva Ganesan, Marie Macnee, Tobias Brünger, Rhys H Thomas, Michael Talkowski, Epi25 Collaborative, Ingo Helbig, Costin Leu, Dennis Lal

Faculty, Staff and Student Publications

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, …

Metastatic Infiltration Of Nervous Tissue And Periosteal Nerve Sprouting In Multiple Myeloma-Induced Bone Pain In Mice And Human, Marta Diaz-Delcastillo, Oana Palasca, Tim T Nemler, Didde M Thygesen, Norma A Chávez-Saldaña, Juan A Vázquez-Mora, Lizeth Y Ponce Gomez, Lars Juhl Jensen, Holly Evans, Rebecca E Andrews, Aritri Mandal, David Neves, Patrick Mehlen, James P Caruso, Patrick M Dougherty, Theodore J Price, Andrew Chantry, Michelle A Lawson, Thomas L Andersen, Juan M Jimenez-Andrade, Anne-Marie Heegaard

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin gene-related peptide (CGRP+) and growth associated protein 43 (GAP43+) fibers occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone of male mice and found alterations in pathways associated with …

The Experiences Of Autistic Doctors: A Cross-Sectional Study, Sebastian C.K. Shaw, Alexander Fossi, Laura A. Carravallah, Kai Rabenstein, Wendy Ross, Mary Doherty

Jefferson Autism Center of Excellence Faculty Papers

Introduction: Medicine may select for autistic characteristics. As awareness and diagnosis of autism are growing, more medical students and doctors may be discovering they are autistic. No studies have explored the experiences of autistic doctors. This study aimed to fill that gap.

Methods: This is a cross-sectional study. A participatory approach was used to identify the need for the project and to modify a pre-existing survey for use exploring the experiences of autistic doctors.

Results: We received 225 responses. 64% had a formal diagnosis of autism. The mean age of receiving a formal diagnosis was 36 (range 3–61). Most were …

Secondary Analysis Of A James Lind Alliance Priority Setting Partnership To Facilitate Knowledge Translation In Degenerative Cervical Myelopathy (Dcm): Insights From Ao Spine Recode-Dcm, Benjamin Davies, Jamie Brannigan, Oliver D. Mowforth, Danyal Khan, Angus G.K. Mcnair, Lindsay Tetreault, Iwan Sadler, Ellen Sarewitz, Bizhan Aarabi, Brian Kwon, Toto Gronlund, Vafa Rahimi-Movaghar, Carl Moritz Zipser, Peter John Hutchinson, Shekar Kurpad, James S. Harrop, Jefferson R. Wilson, James D. Guest, Michael G. Fehlings, Mark R.N. Kotter

Department of Neurosurgery Faculty Papers

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM).

DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM.

PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation.

RESULTS: The survey was completed by 423 individuals from 68 different countries. A total …

Efficacy And Safety Of Elamipretide In Individuals With Primary Mitochondrial Myopathy: The Mmpower-3 Randomized Clinical Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce H Cohen, Gregory M Enns, Marni J Falk, Amy Goldstein, Gráinne Siobhan Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russell Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, David A Brown, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.

METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints …

Nerve Transfer For Restoration Of Lower Motor Neuron-Lesioned Bladder, Urethral, And Anal Sphincter Function In A Dog Model. Part 3. Nicotinic Receptor Characterization, Nagat Frara, Mary F. Barbe, Dania Giaddui, Danielle S. Porreca, Alan S. Braverman, Ekta Tiwari, Attia Ahmad, Justin M. Brown, Benjamin R. Johnston, Stanley F. Bazarek, Michael R. Ruggieri

Department of Neurology Faculty Papers

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6–21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9–13 mo, then reinnervated with 8–12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response …

The Cerebellum Contributes To Generalized Seizures By Altering Activity In The Ventral Posteromedial Nucleus, Jaclyn Beckinghausen, Joshua Ortiz-Guzman, Tao Lin, Benjamin Bachman, Luis E Salazar Leon, Yu Liu, Detlef H Heck, Benjamin R Arenkiel, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Thalamo-cortical networks are central to seizures, yet it is unclear how these circuits initiate seizures. We test whether a facial region of the thalamus, the ventral posteromedial nucleus (VPM), is a source of generalized, convulsive motor seizures and if convergent VPM input drives the behavior. To address this question, we devise an in vivo optogenetic mouse model to elicit convulsive motor seizures by driving these inputs and perform single-unit recordings during awake, convulsive seizures to define the local activity of thalamic neurons before, during, and after seizure onset. We find dynamic activity with biphasic properties, raising the possibility that heterogenous …

Effect Of Reduced Versus Usual Lipid Emulsion Dosing On Bilirubin Neurotoxicity And Neurodevelopmental Impairment In Extremely Preterm Infants: Study Protocol For A Randomized Controlled Trial, Lindsay F Holzapfel, Cody Arnold, Jon E Tyson, Steven M Shapiro, Eric W Reynolds, Claudia Pedroza, Emily K Stephens, Alan Kleinfeld, Andrew H Huber, Matthew A Rysavy, Maria Del Mar Romero Lopez, Amir M Khan

Faculty, Staff and Student Publications

BACKGROUND: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels.

OBJECTIVE: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34-36 weeks gestational age in infants born …

Using Predictive Validity To Compare Associations Between Brain Damage And Behavior, John F Magnotti, Jaclyn S Patterson, Tatiana T Schnur

Faculty, Staff and Student Publications

Lesion-behavior mapping (LBM) provides a statistical map of the association between voxel-wise brain damage and individual differences in behavior. To understand whether two behaviors are mediated by damage to distinct regions, researchers often compare LBM weight outputs by either the Overlap method or the Correlation method. However, these methods lack statistical criteria to determine whether two LBM are distinct versus the same and are disconnected from a major goal of LBMs: predicting behavior from brain damage. Without such criteria, researchers may draw conclusions from numeric differences between LBMs that are irrelevant to predicting behavior. We developed and validated a predictive …

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable …

Targeting Gbm With An Oncolytic Picornavirus Svv-001 Alone And In Combination With Fractionated Radiation In A Novel Panel Of Orthotopic Pdx Models, Huiyuan Zhang, Yuchen Du, Lin Qi, Sophie Xiao, Frank K Braun, Mari Kogiso, Yulun Huang, Frank Huang, Aalaa Abdallah, Milagros Suarez, Sekar Karthick, Nabil M Ahmed, Vita S Salsman, Patricia A Baxter, Jack M Su, Daniel J Brat, Paul L Hellenbeck, Wan-Yee Teo, Akash J Patel, Xiao-Nan Li

Faculty, Staff and Students Publications

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated …

Tiam1 Coordinates Synaptic Structural And Functional Plasticity Underpinning The Pathophysiology Of Neuropathic Pain, Lingyong Li, Qin Ru, Yungang Lu, Xing Fang, Guanxing Chen, Ali Bin Saifullah, Changqun Yao, Kimberley F Tolias

Faculty, Staff and Students Publications

Neuropathic pain is a common, debilitating chronic pain condition caused by damage or a disease affecting the somatosensory nervous system. Understanding the pathophysiological mechanisms underlying neuropathic pain is critical for developing new therapeutic strategies to treat chronic pain effectively. Tiam1 is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendritic and synaptic growth during hippocampal development by inducing actin cytoskeletal remodeling. Here, using multiple neuropathic pain animal models, we show that Tiam1 coordinates synaptic structural and functional plasticity in the spinal dorsal horn via actin cytoskeleton reorganization and synaptic NMDAR stabilization and that these actions are essential for the …

A Bayesian Network Approach To Social And Nonsocial Cognition In Schizophrenia: Are Some Domains More Fundamental Than Others?, Samuel J Abplanalp, Junghee Lee, William P Horan, Robert S Kern, David L Penn, Michael F Green

Faculty, Staff and Student Publications

OBJECTIVES: Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables-and whether specific tasks directly depend on performance in other tasks-is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

STUDY DESIGN: The study sample comprised 173 participants with schizophrenia (71.7% male; 28.3% female). Participants completed 5 social cognitive tasks and the MATRICS Consensus Cognitive Battery. We estimated Bayesian networks using directed acyclic graph structures to examine directional dependencies among the variables.

STUDY RESULTS: After …

Loss Of The Batten Disease Protein Cln3 Leads To Mis-Trafficking Of M6pr And Defective Autophagic-Lysosomal Reformation, Alessia Calcagni', Leopoldo Staiano, Nicolina Zampelli, Nadia Minopoli, Niculin J Herz, Giuseppe Di Tullio, Tuong Huynh, Jlenia Monfregola, Alessandra Esposito, Carmine Cirillo, Aleksandar Bajic, Mahla Zahabiyon, Rachel Curnock, Elena Polishchuk, Luke Parkitny, Diego Luis Medina, Nunzia Pastore, Peter J Cullen, Giancarlo Parenti, Maria Antonietta De Matteis, Paolo Grumati, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our …

Treatment Of Adult Spasticity With Botox (Onabotulinumtoxina): Development, Insights, And Impact, Alberto Esquenazi, Wolfgang H. Jost, Catherine C. Turkel, Theodore Wein, Rozalina Dimitrova

Moss-Magee Rehabilitation Papers

Upper and lower limb spasticity (ULS, LLS) often occur following a stroke or in patients with other neurological disorders, leading to difficulties in mobility and daily living and decreased quality of life. Prior to the use of onabotulinumtoxinA, antispastic medications had limited efficacy and often caused sedation. Phenol injections were difficult for physicians to perform, painful, and led to tissue destruction. The success of onabotulinumtoxinA in treating cervical dystonia led to its use in spasticity. However, many challenges characterized the development of onabotulinumtoxinA for adult spasticity. The wide variability in the presentation of spasticity among patients rendered it difficult to …

Phenotype And Genetic Analysis Of Data Collected Within The First Year Of Neurodev, Patricia Kipkemoi, Heesu Ally Kim, Bjorn Christ, Emily O’Heir, Jake Allen, Christina Austin-Tse, Samantha Baxter, Amina Abubakar, Charles Newton, Alicia Martin

Institute for Human Development, East Africa

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev’s first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing …

Occupational Therapists' Perceptions Of Sensory Processing Evaluation Methods, Grace Hong, Jazminne Orozco Arteaga, Karen Park

Summer 2023 Virtual OTD Capstone Symposium

Background: This study aimed to obtain occupational therapists’ (OTs) experiences and perspectives on current evaluation tools who work with clients with sensory processing challenges in their clinical settings. Method: This research was a mixed-method study. Data was collected from surveys (n = 11) which had a mix of nominal, interval, close-ended, and open-ended questions. Following survey completion, participants were given the option to complete a semi-structured interview (n = 2) consisting of open-ended questions to clarify survey responses and gather additional information about their experiences. Results: The results indicated a high number of various barriers and limitations …