Medicine and Health Sciences Commons^™

Coping During The Covid-19 Pandemic Among Young Adults Experiencing Homelessness And Unstable Housing: A Qualitative Study, Karen Divalerio Gibbs, Jennifer Torres Jones, Whitney Lamark, Sarah Abdulmooti, Lauren Bretz, Kelly D Kearney, Sarah Carter Narendorf, Diane M Santa Maria

Faculty, Staff and Students Publications

BACKGROUND: Young adults experiencing homelessness (YAEH) experience more stressors compared to housed peers, yet little is known about the impact of the COVID-19 pandemic on these youth. The purpose of this qualitative study was to explore how YAEH perceived the pandemic's impact on their well-being and coping.

METHODS: YAEH were recruited from those participating in an HIV prevention study. Semi-structured interviews were conducted and analysis was guided by Lazarus and Folkman's transactional theory of stress and coping.

RESULTS: Four major themes were identified from interviews with 40 youth: (1) ongoing harms, (2) COVID-19 as a stressor, (3) mental health impacts, …

The Many Faces Of Arrhythmogenic Cardiomyopathy: An Overview, Hanna J Tadros, Christina Y Miyake, Debra L Kearney, Jeffrey J Kim, Susan W Denfield

Faculty, Staff and Students Publications

Arrhythmogenic cardiomyopathy (AC) is a disease that involves electromechanical uncoupling of cardiomyocytes. This leads to characteristic histologic changes that ultimately lead to the arrhythmogenic clinical features of the disease. Initially thought to affect the right ventricle predominantly, more recent data show that it can affect both the ventricles or the left ventricle alone. Throughout the recent era, diagnostic modalities and criteria for AC have continued to evolve and our understanding of its clinical features in different age groups as well as the genotype to the phenotype correlations have improved. In this review, we set out to detail the epidemiology, etiologies, …

Hereditary Pulmonary Arterial Hypertension Burden In Pediatrics: A Single Referral Center Experience, Maki Ishizuka, Wenxin Zou, Elise Whalen, Erin Ely, Ryan D Coleman, Dolores H Lopez-Terrada, Daniel J Penny, Yuxin Fan, Nidhy P Varghese

Faculty, Staff and Students Publications

INTRODUCTION: Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center.

METHODS: Children with PAH panel administered by the John Welsh Cardiovascular Diagnostic Laboratory at Texas Children's Hospital and Baylor College of Medicine in Houston, Texas between October 2012 to August 2021 were included into this study. Medical records were retrospectively reviewed for clinical correlation.

RESULTS: Sixty-six children with PAH …

Unmasking Barriers In The Delivery Of Preconception Counseling And Contraception Provision For Patients With Type 1 Or Type 2 Diabetes, Layla A Abushamat, Lauren Sayres, Rebecca Jeffers, Chloe Nielsen, Linda A Barbour, Adnin Zaman

Faculty, Staff and Students Publications

No abstract provided.

Cerebrospinal Fluid Biomarkers Provide Evidence For Kidney-Brain Axis Involvement In Cerebral Malaria Pathogenesis, Andrea L Conroy, Dibyadyuti Datta, Robert O Opoka, Anthony Batte, Paul Bangirana, Adnan Gopinadhan, Kagan A Mellencamp, Ayse Akcan-Arikan, Richard Idro, Chandy C John

Faculty, Staff and Students Publications

INTRODUCTION: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.

METHODS: We evaluated 30 cerebrospinal fluid (CSF) markers …

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations, Robert T Russell, Joseph R Esparaz, Michael A Beckwith, Peter J Abraham, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization …

Diagnostic Performance Of Point-Of-Use Ultrasound Of Resuscitation Outcomes: A Systematic Review And Meta-Analysis Of 3265 Patients, Maciej Dudek, Lukasz Szarpak, Frank W Peacock, Aleksandra Gasecka, Tomasz Michalski, Pawel Wroblewski, Halla Kaminska, Gabriela Borkowska, Ewa Skrzypek, Adam Smereka, Jaroslaw Meyer-Szary, Sylwia Marciniak, Mariola Malecka

Faculty, Staff and Students Publications

BACKGROUND: Echocardiography in the setting of resuscitation can provide information as to the cause of the cardiac arrest, as well as indicators of futility. This systematic review and meta-analysis were performed to determine the value of point-of-care ultrasonography (PoCUS) in the assessment of survival for adult patients with cardiac arrest.

METHODS: This meta-analysis was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, Cochrane have been searched from databases inception until March 2nd 2021. The search was limited to adult patients with cardiac arrest and without publication dates or …

Meta-Analysis Of Chest Compression-Only Versus Conventional Cardiopulmonary Resuscitation By Bystanders For Adult With Out-Of-Hospital Cardiac Arrest, Karol Bielski, Jacek Smereka, Jaroslaw Chmielewski, Michal Pruc, Francesco Chirico, Aleksandra Gasecka, Nataliia Litvinova, Milosz J Jaguszewski, Grazyna Nowak-Starz, Zubaid Rafique, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: According to the guidelines of cardiopulmonary resuscitation (CPR) conducted by bystanders, two methods of CPR are feasible: standard CPR (sCPR) with mouth-to-mouth ventilations and continuous chest compression-only CPR (CCC) without rescue breathing. The goal herein, was to evaluate the effect of sCPR (30:2) and CCC on resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) patients.

METHODS: This study was a systematic review and meta-analysis. Using standardized criteria, Pub- Med, Web of Science, Scopus, EMBASE and Cochrane Collaboration were searched for trials assessing the effect of sCPR vs. CCC on resuscitation outcomes after adult OHCA. Random-effects model meta-analysis was …

Enrollment Of Underrepresented Racial And Ethnic Groups In The Rare And Atypical Diabetes Network (Radiant), Mustafa Tosur, Laura Gandolfo, Ashok Balasubramanyam, Rochelle N Naylor, Toni I Pollin, Neda Rasouli, Sara J Cromer, John B Buse, Maria J Redondo, Radiant Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG.

MATERIALS AND METHODS: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible.

RESULTS: …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Implication Of The 2014 World Health Organization Integrated Management Of Childhood Illness Pneumonia Guidelines With And Without Pulse Oximetry Use In Malawi: A Retrospective Cohort Study, Shubhada Hooli, Charles Makwenda, Norman Lufesi, Tim Colbourn, Tisungane Mvalo, Eric D Mccollum, Carina King

Faculty, Staff and Students Publications

BACKGROUND: Under-5 pneumonia mortality remains high in low-income countries. In 2014 the World Health Organization (WHO) advised that children with chest indrawing pneumonia, but without danger signs or peripheral oxygen saturation (SpO

METHODS: Secondary analysis of 13,413 under-5 pneumonia cases in Malawi. Pneumonia associated case fatality ratios (CFR) were calculated by disease severity under the assumptions of the 2005 and 2014 WHO Integrated Management of Childhood Illness (IMCI) guidelines, with and without pulse oximetry. We investigated if pulse oximetry readings were missing not at random (MNAR).

RESULTS: The CFR of patients classified as having non-severe pneumonia per the 2014 IMCI …

Size Distributions Of Intracellular Condensates Reflect Competition Between Coalescence And Nucleation, Daniel S W Lee, Chang-Hyun Choi, David W Sanders, Lien Beckers, Joshua A Riback, Clifford P Brangwynne, Ned S Wingreen

Faculty, Staff and Students Publications

Phase separation of biomolecules into condensates has emerged as a mechanism for intracellular organization and affects many intracellular processes, including reaction pathways through the clustering of enzymes and pathway intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear. Here we show that both native and synthetic condensates display an exponential size distribution, which is captured by Monte Carlo simulations of fast nucleation followed by coalescence. In contrast, pathological aggregates exhibit a power-law size distribution. These distinct behaviours reflect the relative importance …

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Sphingolipids In Neurodegenerative Diseases, Xueyang Pan, Debdeep Dutta, Shenzhao Lu, Hugo J Bellen

Faculty, Staff and Students Publications

Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we …

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …

Differential Regulation Of Skeletal Stem/Progenitor Cells In Distinct Skeletal Compartments, Jea Giezl Niedo Solidum, Youngjae Jeong, Francisco Heralde, Dongsu Park

Faculty, Staff and Students Publications

Skeletal stem/progenitor cells (SSPCs), characterized by self-renewal and multipotency, are essential for skeletal development, bone remodeling, and bone repair. These cells have traditionally been known to reside within the bone marrow, but recent studies have identified the presence of distinct SSPC populations in other skeletal compartments such as the growth plate, periosteum, and calvarial sutures. Differences in the cellular and matrix environment of distinct SSPC populations are believed to regulate their stemness and to direct their roles at different stages of development, homeostasis, and regeneration; differences in embryonic origin and adjacent tissue structures also affect SSPC regulation. As these SSPC …

Variantsurvival: A Tool To Identify Genotype-Treatment Response, Thomas Krannich, Marina Herrera Sarrias, Hiba Ben Aribi, Moustafa Shokrof, Alfredo Iacoangeli, Ammar Al-Chalabi, Fritz J Sedlazeck, Ben Busby, Ahmad Al Khleifat

Faculty, Staff and Students Publications

Associated Data

Cloud-Native Distributed Genomic Pileup Operations, Marek Wiewiórka, Agnieszka Szmurło, Paweł Stankiewicz, Tomasz Gambin

Faculty, Staff and Students Publications

MOTIVATION: Pileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computational nodes.

RESULTS: Here, we present a scalable, distributed and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) …

Ageing And Rejuvenation Of Tissue Stem Cells And Their Niches, Anne Brunet, Margaret A Goodell, Thomas A Rando

Faculty, Staff and Students Publications

Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular …

A Population-Based Assessment Of Metastatic Hepatoblastoma In Texas Reveals Ethnic Disparities, Andres F Espinoza, Michael E Scheurer, Tiffany M Chambers, Sanjeev A Vasudevan, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Hepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.

METHODS: Information on children diagnosed with hepatoblastoma at 0-19 years of age for the period of …

Factors Associated With Nonsyndromic Anotia And Microtia, Texas, 1999–2014, Jeremy M Schraw, J P Woodhouse, Renata H Benjamin, Charles J Shumate, Joanne Nguyen, Mark A Canfield, A J Agopian, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).

METHODS: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.

RESULTS: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with …

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Disease Modeling Of Adamts9-Related Nephropathy Using Kidney Organoids Reveals Its Roles In Tubular Cells And Podocytes, Seyoung Yu, Yo Jun Choi, John Hoon Rim, Hye-Youn Kim, Nasim Bekheirnia, Sarah Jane Swartz, Hongzheng Dai, Shen Linda Gu, Soyeon Lee, Ryuichi Nishinakamura, Friedhelm Hildebrandt, Mir Reza Bekheirnia, Heon Yung Gee

Faculty, Staff and Students Publications

INTRODUCTION: Mutations in ADAMTS9 cause nephronophthisis-related ciliopathies (NPHP-RC), which are characterized by multiple developmental defects and kidney diseases. Patients with NPHP-RC usually have normal glomeruli and negligible or no proteinuria. Herein, we identified novel compound-heterozygous ADAMTS9 variants in two siblings with NPHP-RC who had glomerular manifestations, including proteinuria.

METHODS: To investigate whether ADAMTS9 dysfunction causes NPHP and glomerulopathy, we differentiated ADAMTS9 knockout human induced pluripotent stem cells (hiPSCs) into kidney organoids. Single-cell RNA sequencing was utilized to elucidate the gene expression profiles from the ADAMTS9 knockout kidney organoids.

RESULTS:ADAMTS9 knockout had no effect on nephron differentiation; however, it reduced …

Subcortical Functional Connectivity And Its Association With Walking Performance Following Deployment Related Mild Tbi, Mary R Newsome, Sarah L Martindale, Nicholas Davenport, Emily L Dennis, Marlene Diaz, Carrie Esopenko, Cooper Hodges, George R Jackson, Qisheng Liu, Kimbra Kenney, Andrew R Mayer, Jared A Rowland, Randall S Scheibel, Joel L Steinberg, Brian A Taylor, David F Tate, J Kent Werner, William C Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

INTRODUCTION: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred.

METHODS: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, …

Codon-Optimized Tdp-43 Mediates Neurodegeneration In A Drosophila Model Of Als/Ftld, Tanzeen Yusuff, Ya-Chu Chang, Tzu-Kang Sang, George R Jackson, Shreyasi Chatterjee

Faculty, Staff and Students Publications

Transactive response DNA binding protein-43 (TDP-43) is known to mediate neurodegeneration associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The exact mechanism by which TDP-43 exerts toxicity in the brains, spinal cord, and lower motor neurons of affected patients remains unclear. In a novel Drosophila melanogaster model, we report gain-of-function phenotypes due to misexpression of insect codon-optimized version of human wild-type TDP-43 (CO-TDP-43) using both the binary GAL4/UAS system and direct promoter fusion constructs. The CO-TDP-43 model showed robust tissue specific phenotypes in the adult eye, wing, and bristles in the notum. Compared to non-codon optimized …

Peripherally-Induced Movement Disorders: An Update, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.

METHODS: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 …

Establishing An Online Resource To Facilitate Global Collaboration And Inclusion Of Underrepresented Populations: Experience From The Mjff Global Genetic Parkinson’S Disease Project, Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia De Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart Van De Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, Christine Klein

Faculty, Staff and Students Publications

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, …

Hippocampal Δfosb Expression Is Associated With Cognitive Impairment In A Subgroup Of Patients With Childhood Epilepsies, Chia-Hsuan Fu, Jason C You, Carrie Mohila, Robert A Rissman, Daniel Yoshor, Angela N Viaene, Jeannie Chin

Faculty, Staff and Students Publications

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of ΔFosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of ΔFosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and …