Medical Specialties Commons^™

Adipose Tissue Lymphocytes And Obesity, Feng Gao, Benjamin Litchfield, Huaizhu Wu

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in adipose tissue (AT), mainly evidenced by infiltration and phenotypic changes of various types of immune cells. Macrophages are the major innate immune cells and represent the predominant immune cell population within AT. Lymphocytes, including T cells and B cells, are adaptive immune cells and constitute another important immune cell population in AT. In obesity, CD8+ effector memory T cells, CD4+ Th1 cells, and B2 cells are increased in AT and promote AT inflammation, while regulatory T cells and Th2 cells, which usually function as immune regulatory or type 2 inflammatory cells, are reduced …

An Interactive, Case-Based Workshop On The Patient Experience For Internal Medicine Residents, Julian Swanson, Doris Lin, Kristen A Staggers, Priti Dangayach

Faculty, Staff and Students Publications

INTRODUCTION: The technological revolution has narrowed the information gap between physician and patient. This has led to an evolution in medicine from paternalistic to patient-centric, with health care systems now prioritizing patient experience to achieve higher satisfaction scores. Therefore, it is imperative to start early in educating trainees on how to best address the holistic needs of the patient while also delivering high-quality care.

METHODS: We implemented a 1-hour workshop that was repeated weekly over 8 weeks to capture all internal medicine residents in our program. During the workshop, we reviewed the historical evolution of patient care from paternalistic to …

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal, Prasanti A Kotta, Ajit K Koduri, Jeffrey Berman, Veronica V Rosen, Waleed T Kayani

Faculty, Staff and Students Publications

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Risk Factors, Incidence, And Outcomes Associated With Clinically Significant Airway Ischemia, Gloria Li, Zejian Liu, Marcelo Salan-Gomez, Emma Keeney, Ethan D'Silva, Babith Mankidy, Andres Leon, Aladdein Mattar, Abdusallam Elsennousi, Jennalee Coster, Anupam Kumar, Bruno Rodrigues, Meng Li, Alexis Shafii, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for …

Using Noninvasive Clinical Parameters To Predict Mortality And Morbidity After Cardiac Interventions In Patients With Cirrhosis: A Systematic Review, Christo Mathew, Ankur Patel, George Cholankeril, Avegail Flores, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease commonly affects advanced liver disease patients. They undergo cardiac interventions to improve cardiac outcomes. Cirrhosis increases complication risk, including bleeding, renal and respiratory failure, and further decompensation, including death, posing a clinical dilemma to proceduralists. Predicting outcomes is crucial in managing patients with cirrhosis. Our aim was to systematically review clinical parameters to assess the mortality and complication risk in patients with cirrhosis undergoing cardiac interventions.

METHODS: We searched cirrhosis and cardiovascular intervention terminology in PubMed and Excerpta Medica Database (EMBASE) from inception to January 8, 2023. We included studies reporting clinical scores (e.g. Model for End-stage …

Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Joselyn Rojas-Quintero, Scott A Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino

Faculty, Staff and Students Publications

Rationale

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.

Objectives

To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.

Methods

Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. …

Cffdna Screening For Niemann-Pick Disease, Type C1: A Case Series, Sydney A Lau, Romy I Fawaz, Robert Rigobello, Shahad Bawazeer, Nouf M Alajaji, Eissa Faqeih, Yanchun Li, Yanming Feng, Fan Xia, Christine M Eng, Malak Abedalthagafi

Faculty, Staff and Students Publications

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann-Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or …

Case Report: An Association Of Left Ventricular Outflow Tract Obstruction With 5p Deletions, Kira Mascho, Svetlana A Yatsenko, Cecilia W Lo, Xinxiu Xu, Jennifer Johnson, Lindsey R Helvaty, Stephanie Burns Wechsler, Chaya N Murali, Seema R Lalani, Vidu Garg, Jennelle C Hodge, Kim L Mcbride, Stephanie M Ware, Jiuann-Huey Ivy Lin

Faculty, Staff and Students Publications

INTRODUCTION: 5p deletion syndrome, also called Cri-du-chat syndrome 5p is a rare genetic syndrome with reports up to 36% of patients are associated with congenital heart defects. We investigated the association between left outflow tract obstruction and Cri-du-chat syndrome.

METHODS: A retrospective review of the abnormal microarray cases with congenital heart defects in Children's Hospital of Pittsburgh and the Cytogenomics of Cardiovascular Malformations Consortium.

RESULTS: A retrospective review at nine pediatric centers identified 4 patients with 5p deletions and left outflow tract obstruction (LVOTO). Three of these patients had additional copy number variants. We present data suggesting an association of …

Human Plcg2 Haploinsufficiency Results In A Novel Natural Killer Cell Immunodeficiency, Joshua B Alinger, Emily M Mace, Justin R Porter, Annelise Y Mah-Som, Allyssa L Daugherty, Stephanie Li, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Albert Yao, Ivan K Chinn, James R Lupski, Mohammad Ehlayel, Michael Keller, Greg R Bowman, Megan A Cooper, Jordan S Orange, Anthony R French

Faculty, Staff and Students Publications

Background:

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in NK cells, lymphocytes which recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK cell and B cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date.

Objective:

We aimed to identify the genetic cause of NK cell immunodeficiency in two families, and herein describe the functional consequences of two novel loss-of-function …

Identification Of Constrained Sequence Elements Across 239 Primate Genomes, Lukas F K Kuderna, Jacob C Ulirsch, Sabrina Rashid, Mohamed Ameen, Laksshman Sundaram, Glenn Hickey, Anthony J Cox, Hong Gao, Arvind Kumar, Francois Aguet, Matthew J Christmas, Hiram Clawson, Maximilian Haeussler, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rouselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Ioannis Karakikes, Kevin C Wang, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Adam Siepel, Anshul Kundaje, Benedict Paten, Kerstin Lindblad-Toh, Jeffrey Rogers, Tomas Marques Bonet, Kyle Kai-How Farh

Faculty, Staff and Students Publications

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of …

Research Participants' Perspectives On Precision Diagnostics For Alzheimer's Disease, Hadley Stevens Smith, Jill O Robinson, Ariel Levchenko, Stacey Pereira, Belen Pascual, Kathleen Bradbury, Victoria Arbones, Jamie Fong, Joshua M Shulman, Amy L Mcguire, Joseph Masdeu

Faculty, Staff and Students Publications

BACKGROUND: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

OBJECTIVE: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

METHODS: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results. We analyzed responses …

Idppub: Illuminating The Dark Phosphoproteome Through Pubmed Mining, Sara R Savage, Yaoyun Zhang, Eric J Jaehnig, Yuxing Liao, Zhiao Shi, Huy Anh Pham, Hua Xu, Bing Zhang

Faculty, Staff and Students Publications

Global phosphoproteomics experiments quantify tens of thousands of phosphorylation sites. However, data interpretation is hampered by our limited knowledge on functions, biological contexts, or precipitating enzymes of the phosphosites. This study establishes a repository of phosphosites with associated evidence in biomedical abstracts, using deep learning-based natural language processing techniques. Our model for illuminating the dark phosphoproteome through PubMed mining (IDPpub) was generated by fine-tuning BioBERT, a deep learning tool for biomedical text mining. Trained using sentences containing protein substrates and phosphorylation site positions from 3000 abstracts, the IDPpub model was then used to extract phosphorylation sites from all MEDLINE abstracts. …

Phenotypic And Functional Assessment Of Two Novel Kcnq2 Gain-Of-Function Variants Y141n And G239s And Effects Of Amitriptyline Treatment, Allan Bayat, Stefano Iavarone, Francesco Miceli, Anne V Jakobsen, Katrine M Johannesen, Marina Nikanorova, Rafal Ploski, Krystyna Szymanska, Robert Flamini, Edward C Cooper, Sarah Weckhuysen, Maurizio Taglialatela, Rikke S Møller

Faculty, Staff and Students Publications

While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex phenotype that precludes neonatal-onset epilepsy. In the present work, the clinical features of three patients carrying a de novo KCNQ2 Y141N (n = 1) or G239S variant (n = 2) respectively, are described. All three patients had a mild global developmental delay, with prominent language deficits, and strong activation of interictal epileptic activity during sleep. Epileptic seizures were not reported. The absence of neonatal seizures suggested a GoF effect and prompted functional testing of the variants. In vitro whole-cell …

Scientific Impact Of The National Birth Defects Prevention Network Multistate Collaborative Publications, Jacqueline T Bascom, Sara B Stephens, Philip J Lupo, Mark A Canfield, Russell S Kirby, Eirini Nestoridi, Jason L Salemi, Cara T Mai, Wendy N Nembhard, Nina E Forestieri, Paul A Romitti, Amanda M St Louis, A J Agopian

Faculty, Staff and Students Publications

BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact.

METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated.

RESULTS: …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Neutrophil-Derived Activin-A Moderates Their Pro-Netotic Activity And Attenuates Collateral Tissue Damage Caused By Influenza A Virus Infection, Georgios Divolis, Evgenia Synolaki, Athanasia Doulou, Ariana Gavriil, Christina C Giannouli, Anastasia Apostolidou, Martyn L Foster, Martin M Matzuk, Panagiotis Skendros, Ioanna-Evdokia Galani, Paschalis Sideras

Faculty, Staff and Students Publications

BACKGROUND: Pre-neutrophils, while developing in the bone marrow, transcribe the Inhba gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood.

METHODS:To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (S100a8-Cre/Inhba fl/fl mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, …

Developing A Pathway To Clinical Trials For Cacna1a-Related Epilepsies: A Patient Organization Perspective, Pangkong M Fox, Sunitha Malepati, Lisa Manaster, Elsa Rossignol, Jeffrey L Noebels

Faculty, Staff and Students Publications

CACNA1A-related disorders are rare neurodevelopmental disorders linked to variants in the CACNA1A gene. This gene encodes the α1 subunit of the P/Q-type calcium channel Cav2.1, which is globally expressed in the brain and crucial for fast synaptic neurotransmission. The broad spectrum of CACNA1A-related neurological disorders includes developmental and epileptic encephalopathies, familial hemiplegic migraine type 1, episodic ataxia type 2, spinocerebellar ataxia type 6, together with unclassified presentations with developmental delay, ataxia, intellectual disability, autism spectrum disorder, and language impairment. The severity of each disorder is also highly variable. The spectrum of CACNA1A-related seizures is broad across both loss-of-function and gain-of-function …

Combined Bioinformatic And Splicing Analysis Of Likely Benign Intronic And Synonymous Variants Reveals Evidence For Pathogenicity, Owen R Hirschi, Stephanie A Felker, Surya P Rednam, Kelly L Vallance, D Williams Parsons, Angshumoy Roy, Gregory M Cooper, Sharon E Plon

Faculty, Staff and Students Publications

PURPOSE: Clinical variant analysis pipelines likely have poor sensitivity to the effects on splicing from variants beyond 10 to 20 bases of exon-intron boundaries. Here, we demonstrate the value of SpliceAI to inform curation of rare variants previously classified as benign/likely benign (B/LB) under current guidelines.

METHODS: Exome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.20), and scored >10 by combined annotation-dependent depletion. Rare synonymous or intronic B/LB variants in 61 genes submitted to ClinVar were …

Bi-Allelic Variants In Cep295 Cause Seckel-Like Syndrome Presenting With Primary Microcephaly, Developmental Delay, Intellectual Disability, Short Stature, Craniofacial And Digital Abnormalities, Niu Li, Yufei Xu, Hongzhu Chen, Jingqi Lin, Lama Alabdi, Mir Reza Bekheirnia, Guoqiang Li, Yoel Gofin, Nasim Bekheirnia, Eissa Faqeih, Lina Chen, Guoying Chang, Jie Tang, Ruen Yao, Tingting Yu, Xiumin Wang, Wei Fu, Qihua Fu, Yiping Shen, Fowzan S Alkuraya, Keren Machol, Jian Wang

Faculty, Staff and Students Publications

BACKGROUND: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology.

METHODS: Whole-exome sequencing was performed to screen for pathogenic variants in patients with severe microcephaly. Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying pathomechanisms, including centriole/centrosome development, cell cycle and proliferation changes, and ciliogenesis. Complementary experiments using CEP295 mRNA were performed to determine the pathogenicity of the identified missense variant. …

Tremor In Cervical Dystonia, Sinem Balta Beylergil, Krishna Nikhil Mukunda, Mohamed Elkasaby, Joel S Perlmutter, Stewart Factor, Tobias Bäumer, Jeanne Feurestein, Erika Shelton, Steven Bellows, Joseph Jankovic, Abhimanyu Mahajan, Tila Wamer-Rosen, Stephen G Reich, Aparna Wagle Shukla, Irene Malaty, Alberto Espay, Kevin Duque, Mark S Ledoux, Rachel Saunders-Pullman, Katherine Leaver, Samuel Frank, Alexander Pantelyat, Victor Fung, Sarah Pirio Richardson, Brian Berman, Natividad Stover, Andres Deik, William Ondo, Christopher Groth, Hyder A Jinnah, Aasef G Shaikh

Faculty, Staff and Students Publications

BACKGROUND: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.

METHODS: We analyzed the largest cohort of CD patients (

RESULTS: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was …

Use Of Botulinum Toxin In The Management Of Dystonia In Parkinson’S Disease, Charenya Anandan, Joseph Jankovic

Faculty, Staff and Students Publications

Botulinum toxin is one of the most potent neurotoxins, but when injected into an overactive muscle, it can transiently alleviate an involuntary movement, such as dystonia. The primary aim of this article is to provide a comprehensive review of the various forms of dystonia observed in patients with Parkinson's disease who can benefit from a therapeutic trial of botulinum toxin. Although most of these indications are not supported by randomized controlled clinical trials and, therefore, not approved by the Food and Drug Administration, there are many open-label trials supporting a large body of empirical experience testifying to the benefits of …

Delivering Multidisciplinary Rehabilitation Care In Parkinson's Disease: An International Consensus Statement, Jennifer G Goldman, Daniele Volpe, Terry D Ellis, Mark A Hirsch, Julia Johnson, Julia Wood, Ana Aragon, Roberta Biundo, Alessandro Di Rocco, Glenn S Kasman, Robert Iansek, Janis Miyasaki, Victor M Mcconvey, Marten Munneke, Serge Pinto, Karen A St Clair, Santiago Toledo, Michele K York, Ronnie Todaro, Nicole Yarab, Kristin Wallock

Faculty, Staff and Students Publications

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD.

OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was …

Ultradian Rhythms In Accelerometric And Autonomic Data Vary Based On Seizure Occurrence In Paediatric Epilepsy Patients, Solveig Vieluf, Sarah Cantley, Vaishnav Krishnan, Tobias Loddenkemper

Faculty, Staff and Students Publications

Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than 24 hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically. Using a wearable device, we recorded heart rate, body temperature, electrodermal activity and limb accelerometry in patients admitted to the paediatric epilepsy monitoring unit. In our case–control design, we included recordings from 29 patients with tonic–clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. …

Screening For Adhd In Adult Patients With Epilepsy: Prevalence Of Symptoms And Challenges To Diagnosis, Trung Nguyen, Emily Xiao, Allison Clark, Afroz Shamim, Atul Maheshwari

Faculty, Staff and Students Publications

OBJECTIVE: Given the complex nature of seizure disorders and their treatments, ADHD may be underdiagnosed in this population. We hypothesized that a higher percentage of patients presenting to a seizure clinic would endorse ADHD symptoms compared to rates reported in the general population and that formal screening for ADHD symptoms would identify patients with previously undiagnosed comorbid ADHD.

METHODS: In this study, we surveyed 312 adults in a seizure clinic using the Adult ADHD Self-Report Scale (ASRS-v1.1).

RESULTS: We found that 90 patients (28.8%) screened positive with the ASRS-v1.1, but only nine of these patients were able to complete neuropsychological …

Validation Of A New Patient-Reported Outcome Measure Of The Functional Impact Of Essential Tremor On Activities Of Daily Living, Ludy C Shih, Michael T Stevenson, Steven Bellows, Alfonso Fasano, Sheng-Han Kuo, Kelly E Lyons, Henry Moore, Holly A Shill, Aparna Wagle Shukla, Carlos Singer, Rodger J Elble

Faculty, Staff and Students Publications

BACKGROUND: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines.

OBJECTIVE: Develop and validate a TETRAS PRO subscale.

METHODS: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for …

Multiple Sclerosis In Central America And Caribbean Countries: Frequency And Clinical Characterization Of An Emergent Disease, Fernando Gracia, Deyanira A Ramírez Navarro, Nicia E Ramírez Sánchez, Roberto Weiser, Alexander Parajeles-Vindas, Ligia I Portillo Rivera, Ericka López Torres, Luis A García Valle, Alfredo Sanabria-Castro, César Abdón López, Pahola Araujo, Maria J Ayerdis Zamora, Andrea Balmaceda-Meza, Aron Benzadon Cohen, Awilda Candelario Cueto, Diego Castillo, Romy Castro-Escobar, Karla Z Corea Urbina, Anyeri De Peña Rivas, Octavio Duarte Sotelo, Temís Enamorado Claros, José L Giroud Benítez, Karla Gracia, Mario Larreategui, Jorge A Martínez Cerrato, Josmarlin P Medina Báez, Carlos E Menjivar Samayoa, Gustavo Miranda-Loria, Priscilla Monterrey-Alvarez, Lilliam A Morales Arguello, Michelle Ortiz, Carlos D Pérez Baldioceda, Lizeth Pinilla Aguilar, Luis C Rodríguez Salinas, Virginia Rodríguez-Moreno, Sebastián Rojas-Chaves, Norbel Román-Garita, Biany Santos Pujols, Carlos Valderrama, Ivonne Van Sijtveld, Indhira Zabala Angeles, Victor M Rivera, Blas Armien

Faculty, Staff and Students Publications

BACKGROUND: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population.

METHODS AND RESULTS: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS …

A Dual Target Molecular Magnetic Resonance Imaging Probe For Noninvasive Profiling Of Pathologic Alpha-Synuclein And Microgliosis In A Mouse Model Of Parkinson’S Disease, Xianwei Sun, Andrew Badachhape, Prajwal Bhandari, Jeannie Chin, Ananth Annapragada, Eric Tanifum

Faculty, Staff and Students Publications

The pathogenesis of Parkinson’s disease (PD) is characterized by progressive deposition of alpha-synuclein (α-syn) aggregates in dopaminergic neurons and neuroinflammation. Noninvasive in vivo imaging of α-syn aggregate accumulation and neuroinflammation can elicit the underlying mechanisms involved in disease progression and facilitate the development of effective treatment as well as disease diagnosis and prognosis. Here we present a novel approach to simultaneously profile α-syn aggregation and reactive microgliosis in vivo, by targeting oligomeric α-syn in cerebrospinal fluid with nanoparticle bearing a magnetic resonance imaging (MRI), contrast payload. In this proof-of-concept report we demonstrate, in vitro, that microglia and neuroblastoma …

Night-Time Neuronal Activation Of Cluster N In A North American Songbird\, Jennifer Rudolf, Natalie Philipello, Tamara Fleihan, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Night-migrating songbirds utilize the Earth's magnetic field to help navigate to and from their breeding sites each year. A region of the avian forebrain called Cluster N has been shown to be activated during night migratory behavior and it has been implicated in processing geomagnetic information. Previous studies with night-migratory European songbirds have shown that neuronal activity at Cluster N is higher at night than during the day. Comparable work in North American migrants has only been performed in one species of swallows, so extension of examination for Cluster N in other migratory birds is needed. In addition, it is …

Cisplatin Vestibulotoxicity: A Current Review, Tamara Fleihan, Marc Elie Nader, J David Dickman

Faculty, Staff and Students Publications

Cisplatin, a commonly used chemotherapy drug, is well-established for its ototoxic effects, primarily attributed to the damage it inflicts on cochlear hair cells. However, its impact on the vestibular system remains inadequately understood. Here, we provide a comprehensive review of existing literature concerning cisplatin-induced vestibulotoxicity. Animal studies have shown that cisplatin induces a vestibular hair cell loss that is dose-dependent, with the severity of damage also varying according to the route of administration. Notably, intratympanic and systemic injections in animal models have manifested significant damage primarily to utricular hair cells, with a lesser degree of damage observed for the other …

Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella

Faculty, Staff and Students Publications

Several optical microscopy methods are now available for characterizing scientific and industrial processes at sub-micron resolution. However, they are often ill-suited for imaging rapid events. Limited by the trade-off between camera frame-rate and sensitivity, or the need for mechanical scanning, current microscopes are optimized for imaging at hundreds of frames-per-second (fps), well-below what is needed in processes such as neuronal signaling or moving parts in manufacturing lines. Here, we present a scan-less technology that allows sub-micrometric imaging at thousands of fps. It is based on combining a single-pixel camera with parallelized encoded illumination. We use two acousto-optic deflectors (AODs) placed …