Medical Specialties Commons^™

Neurodevelopment And Recovery From Wasting, Harriet M. Babikako, Celine Bourdon, Emmie Mbale, Peace Aber, Annet Birabwa, Josephine Chimoyo, Wieger Voskuijl, Zaubina Kazi, John Mukisa, Ali Faisal Saleem

Department of Paediatrics and Child Health

Background and objectives: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness.
Methods: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid-upper arm circumference for age z-score. Neurodevelopment was assessed with the …

Impact Of Dietary Walnuts, A Nutraceutical Option, On Circulating Markers Of Metabolic Dysregulation In A Rodent Cachectic Tumor Model, Lauri O. Byerley, Hsiao Man Chang, Brittany Lorenzen, Jessie Guidry, W. Elaine Hardman

School of Medicine Faculty Publications

Background: Nutraceutical foods, like walnuts which are rich in immunonutrients, can have medicinal benefits. Dietary walnuts have been shown to slow or prevent tumor growth in mice genetically programmed to grow breast or prostate tumors. This study investigated whether walnuts could exert the same preventable effect in a transplantable carcinoma rat model. Methods: Eighteen rats were randomly fed a diet containing walnuts (10% of food by weight), and 36 were fed a diet without walnuts (control) for 21 days. On day 22, 18 control diet rats were switched to the walnut diet. All other animals remained on their same diet. …

Spontaneous Pneumothorax: A Rare Complication Of Neurofibromatosis Type 1 Associated Diffuse Lung Disease, Emma I. Sherfinski, Mark H. Cooper Md, Phd

Marshall Journal of Medicine

The visually striking neurocutaneous findings of neurofibromatosis type 1 (NF1) are well recognized and have been well documented throughout scientific literature. While not uncommon, the pulmonary manifestations of NF1 are unknown to many physicians. Complications of NF1 associated diffuse lung disease (NF-DLD) include pulmonary hypertension, pulmonary artery stenosis, subpleural cysts, and spontaneous pneumothorax. We present a case of a 34-year-old male with NF-DLD found incidentally in adolescence with previous apical bleb repair, presenting nearly twenty years later with spontaneous pneumothorax. In NF1 patients with pulmonary complaints, NF-DLD should be assessed with computed tomography (CT) and physicians should be familiar with …

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

The Importance Of An Early Onset Of Migraine Preventive Disease Control: A Roundtable Discussion, Christopher Gottschalk, Anirban Basu, Andrew Blumenfeld, Bradley Torphy, Michael J. Marmura, Jelena M. Pavlovic, Paula K. Dumas, Nim Lalvani, Dawn C. Buse

Department of Jefferson Headache Center Papers and Presentations

Background: Newly approved migraine preventive therapies have allowed for rapid control of migraine activity, offering potential to minimize the burden of migraine. This report summarizes a roundtable discussion convened to analyze evidence for early onset of prevention, ascertain its clinical relevance, and provide guidance for healthcare professionals in crafting goals and treatment expectations for patients with migraine initiating preventive therapy.

Methods: A virtual roundtable meeting of migraine clinicians, researchers, and patient advocates convened in October 2020. Participants reviewed and discussed data summarizing patient and healthcare professional perceptions of migraine prevention and evidence from the peer-reviewed and gray literature to develop …

Characterization Of A Bioactive Peptide T14 In The Human And Rodent Substantia Nigra: Implications For Neurodegenerative Disease, Susan Adele Greenfield, Giovanni Ferrati, Clive W Coen, Auguste Vadisiute, Zoltan Molnár, Sara Garcia-Rates, Sally Frautschy, Gregory M Cole

Faculty, Staff and Student Publications

The substantia nigra is generally considered to show significant cell loss not only in Parkinson's but also in Alzheimer's disease, conditions that share several neuropathological traits. An interesting feature of this nucleus is that the pars compacta dopaminergic neurons contain acetylcholinesterase (AChE). Independent of its enzymatic role, this protein is released from pars reticulata dendrites, with effects that have been observed in vitro, ex vivo and in vivo. The part of the molecule responsible for these actions has been identified as a 14-mer peptide, T14, cleaved from the AChE C-terminus and acting at an allosteric site on alpha-7 nicotinic receptors, …

Distinct Organization Of Two Cortico-Cortical Feedback Pathways, Shan Shen, Xiaolong Jiang, Federico Scala, Jiakun Fu, Paul Fahey, Dmitry Kobak, Zhenghuan Tan, Na Zhou, Jacob Reimer, Fabian Sinz, Andreas S Tolias

Duncan NRI Faculty and Staff Publications

Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase–followed by a prolonged decrease–in pyramidal …

Cluster Analysis Of Short Sensory Profile Data Reveals Sensory-Based Subgroups In Autism Spectrum Disorder, Ariel M Lyons-Warren, Michael F Wangler, Ying-Wooi Wan

Duncan NRI Faculty and Staff Publications

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks’ MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) …

Rapid Reconstruction Of Neural Circuits Using Tissue Expansion And Light Sheet Microscopy, Joshua L Lillvis, Hideo Otsuna, Xiaoyu Ding, Igor Pisarev, Takashi Kawase, Jennifer Colonell, Konrad Rokicki, Cristian Goina, Ruixuan Gao, Amy Hu, Kaiyu Wang, John Bogovic, Daniel E Milkie, Linus Meienberg, Brett D Mensh, Edward S Boyden, Stephan Saalfeld, Paul W Tillberg, Barry J Dickson

Faculty, Staff and Student Publications

Brain function is mediated by the physiological coordination of a vast, intricately connected network of molecular and cellular components. The physiological properties of neural network components can be quantified with high throughput. The ability to assess many animals per study has been critical in relating physiological properties to behavior. By contrast, the synaptic structure of neural circuits is presently quantifiable only with low throughput. This low throughput hampers efforts to understand how variations in network structure relate to variations in behavior. For neuroanatomical reconstruction, there is a methodological gulf between electron microscopic (EM) methods, which yield dense connectomes at considerable …

Neurodevelopment Assessment Of Small For Gestational Age Children In A Community-Based Cohort From Pakistan, Sabahat Naz, Zahra Hoodbhoy, Ali Jaffar, Sidra Kaleem Jafri, Babar Hasan, Devyani Chowdhury, Melissa Gladstone

Department of Paediatrics and Child Health

Background: Children born small for gestational age (SGA) may experience more long-term neurodevelopmental issues than those born appropriate for gestational age (AGA). This study aimed to assess differences in the neurodevelopment of children born SGA or AGA within a periurban community in Pakistan.
Methods: This was a prospective cohort study in which study participants were followed from the pilot Doppler cohort study conducted in 2018. This pilot study aimed to develop a pregnancy risk stratification model using machine learning on fetal Dopplers. This project identified 119 newborns who were born SGA (2.4±0.4 kg) based on International Fetal and Newborn Growth …

Recombinant Protein Micelles To Block Transduction By Sars-Cov-2 Pseudovirus, Rajarshi Chattaraj, Christina Y Kim, Daeyeon Lee, Daniel A Hammer

Faculty, Staff and Student Publications

The continuing emergence of variants of the SARS-CoV-2 virus requires the development of modular molecular therapies. Here, we engineered a recombinant amphiphilic protein, oleosin, to spontaneously self-assemble into multivalent micellar nanostructures which can block the Spike S1 protein of SARS-CoV-2 pseudoviruses (PVs). Short recombinant proteins like oleosin can be formulated more easily than antibodies and can be functionalized with precision through genetic engineering. We cloned S1-binding mini-protein genes called LCB

Cannabidiol, ∆9 -Tetrahydrocannabinol, And Metabolites In Human Blood By Volumetric Absorptive Microsampling And Lc-Ms/Ms Following Controlled Administration In Epilepsy Patients, Federica Pigliasco, Sara Malaca, Alfredo Fabrizio Lo Faro, Anastasio Tini, Giuliana Cangemi, Alessia Cafaro, Sebastiano Barco, Antonella Riva, Angelica Pisati, Elisabetta Amadori, Pasquale Striano, Adriano Tagliabracci, Marilyn A. Huestis, Francesco Paolo Busardò

Institute of Emerging Health Professions Faculty Papers

Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-tetrahydrocannabinol (THC). While recreational cannabis contains higher THC and lower CBD concentrations, medical cannabis contains THC and CBD in different ratios, along with minor phytocannabinoids, terpenes, flavonoids and other chemicals. A volumetric absorptive microsampling (VAMS) method combined with ultra-high-performance liquid chromatography coupled with mass spectrometry in tandem for quantification of CBD, THC and their respective metabolites: cannabidiol-7-oic acid (7-COOH-CBD); 7-hydroxy-cannabidiol (7-OH-CBD); 6-alpha-hydroxy-cannabidiol (6-α-OH-CBD); and 6-beta-hydroxycannabidiol (6-β-OH-CBD); 11- Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH). After overnight enzymatic glucuronide hydrolysis at 37°C, samples underwent acidic …

Biological Networks And Complexity In Early-Onset Motor Neuron Diseases, Matthew E. R. Butchbach, Rod C. Scott

Department of Pediatrics Faculty Papers

Motor neuron diseases (MNDs) are neuromuscular disorders where the spinal motor neurons–either the cell bodies themselves or their axons–are the primary cells affected. To date, there are 120 different genes that are lost or mutated in pediatric-onset MNDs. Most of these childhood-onset disorders, aside from spinal muscular atrophy (SMA), lack viable therapeutic options. Previous research on MNDs has focused on understanding the pathobiology of a single, specific gene mutation and targeting therapies to that pathobiology. This reductionist approach has yielded therapeutic options for a specific disorder, in this case SMA. Unfortunately, therapies specific for SMA have not been effective against …

Objective Assessment Of Upper-Extremity Motor Functions In Spinocerebellar Ataxia Using Wearable Sensors, Reza Mohammadi-Ghazi, Hung Nguyen, Ram Kinker Mishra, Ana Enriquez, Bijan Najafi, Christopher D Stephen, Anoopum S Gupta, Jeremy D Schmahmann, Ashkan Vaziri

Center on Aging Staff Publications

The study presents a novel approach to objectively assessing the upper-extremity motor symptoms in spinocerebellar ataxia (SCA) using data collected via a wearable sensor worn on the patient’s wrist during upper-extremity tasks associated with the Assessment and Rating of Ataxia (SARA). First, we developed an algorithm for detecting/extracting the cycles of the finger-to-nose test (FNT). We extracted multiple features from the detected cycles and identified features and parameters correlated with the SARA scores. Additionally, we developed models to predict the severity of symptoms based on the FNT. The proposed technique was validated on a dataset comprising the seventeen (n …

Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur

Faculty, Staff and Student Publications

Connected speech recovers to different degrees across people after left hemisphere stroke, but white matter predictors of differential recovery from the acute stage of stroke are unknown. We assessed changes in lexical-syntactic aspects of connected speech in a longitudinal analysis of 40 individuals (18 females) from the acute stage of left hemisphere stroke (within an average of 4 days post-stroke) to subacute (within 2 months) and chronic stages (early: 6 months, late: 1 year) while measuring the extent of acute lesions on white matter tracts to identify tracts predictive of recovery. We found that acute damage to the frontal aslant …

Mapping The Universe Of Eph Receptor And Ephrin Ligand Transcripts In Epithelial And Fiber Cells Of The Eye Lens, Michael P Vu, Catherine Cheng

Faculty, Staff and Student Publications

The eye lens is a transparent, ellipsoid organ in the anterior chamber of the eye that is required for fine focusing of light onto the retina to transmit a clear image. Cataracts, defined as any opacity in the lens, remains the leading cause of blindness in the world. Recent studies in humans and mice indicate that Eph-ephrin bidirectional signaling is important for maintaining lens transparency. Specifically, mutations and polymorphisms in the EphA2 receptor and the ephrin-A5 ligand have been linked to congenital and age-related cataracts. It is unclear what other variants of Ephs and ephrins are expressed in the lens …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Gastric Perforation From A Migrating Ventriculoperitoneal Shunt: A Case Report And Review Of Literature, Alessio Scarascia, Elias Atallah, Maria De Abreu Pineda, Robert H. Rosenwasswer, Kevin Judy

Department of Neurosurgery Faculty Papers

Ventriculoperitoneal (VP) shunts represent a surgical option for patients affected by increased intracranial hypertension when medical management fails or is contraindicated. Complications following implantation include shunt obstruction, infection, over and under drainage, migration or disconnection of the tube, formation of a pseudocyst, and allergy to the silicone tube. We report the case of a 31-year-old woman who presented to the emergency room with nausea and generalized malaise, found to have the distal segment of the VP catheter perforating her gastric wall into the stomach lumen which required surgical intervention. In this report, we describe a rare complication associated with the …

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …

Central Nervous System (Cns) Inflammatory Demyelinating Diseases (Idds) Associated With Covid-19: A Case Series And Review, Parissa Feizi, Kanika Sharma, Shreya R Pasham, Lalit Nirwan, Joe Joseph, Shruti Jaiswal, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD).

METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the …

The Use Of Virtual Tools In Narrowing The Impact Of Health Disparities In Neurology., Jean-Baptist Lepichon, Stephanie Horton, Omar Abdelmoity, Mark A. Hoffman, Emily Cramer, Nirmeen Kishk, Salah Hamada, Ahmed Abdelmoity

Manuscripts, Articles, Book Chapters and Other Papers

The concept of Epilepsy Treatment Gap (ETG) refers to the proportion of people with epilepsy who are not being appropriately treated. The ETG in the USA approaches 10%, with historically underserved populations and rural populations disproportionately affected. The ETG in Low-and Middle-Income Countries (LMIC) is reported to be 5-10 times higher than in high-income countries. The growing availability of reliable internet access offers a unique opportunity to provide better care to children and adults with epilepsy. In this paper we explore various telehealth (TH) initiatives that have leveraged the availability of easy and free access to an internet connection in …

Columnar Metaplasia Of The Esophagus Presenting As Iron Deficiency Anemia In Children With Neurologic Impairment Or Congenital Esophageal Atresia, Melissa R Van Arsdall, Supriya Nair, Lindsay M Moye, Trinh T Nguyen, Zeina M Saleh, J Marc Rhoads

Faculty, Staff and Student Publications

BACKGROUND Columnar metaplasia of the lower esophagus includes both gastric and intestinal metaplasia. Children with severe neurologic impairment and congenital esophageal atresia often have gastroesophageal reflux disease, which can lead to Barrett's esophagus, a form of lower esophageal columnar metaplasia and precursor to esophageal adenocarcinoma, with some, but not all, guidelines specifically requiring the presence of intestinal metaplasia for diagnosis. This case series illustrates how iron deficiency anemia may be the primary symptom of esophageal columnar metaplasia in such children and how upper endoscopy is essential in their initial and ongoing evaluation. CASE REPORT We review 5 cases of columnar …

Intraoperative Changes In Somatosensory Evoked Potentials As A Predictor Of Perioperative Stroke In Carotid Endarterectomy, Justin W. Meinert Bphil, Parthatharasy D. Thirumala Md, Jeffrey R. Balzer Phd, Donald J. Crammond Phd, Eyad E. Saca Md

Tower Health Research Day

No abstract provided.

A Rare Presentation Of Guillain Barre Syndrome (Gbs) Secondary To Pneumococcal Conjugate Vaccination, Michael Juszczak, Jedidah Prum, Anishinder Parkash, William Gleason

Tower Health Research Day

No abstract provided.

De Novo Variants In Frmd5 Are Associated With Developmental Delay, Intellectual Disability, Ataxia, And Abnormalities Of Eye Movement, Shenzhao Lu, Mengqi Ma, Xiao Mao, Carlos A Bacino, Joseph Jankovic, V Reid Sutton, James A Bartley, Xueying Wang, Jill A Rosenfeld, Ana Beleza-Meireles, Jaynee Chauhan, Xueyang Pan, Megan Li, Pengfei Liu, Katrina Prescott, Sam Amin, George Davies, Michael F Wangler, Yuwei Dai, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was …

The Recurrent De Novo C.2011c>T Missense Variant In Mtss2 Causes Syndromic Intellectual Disability, Yan Huang, Gabrielle Lemire, Lauren C Briere, Fang Liu, Marja W Wessels, Xueqi Wang, Matthew Osmond, Oguz Kanca, Shenzhao Lu, Frances A High, Melissa A Walker, Lance H Rodan, Undiagnosed Diseases Network, Care4rare Canada Consortium, Kristin D Kernohan, David A Sweetser, Kym M Boycott, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

MTSS2, also known as MTSS1L, binds to plasma membranes and modulates their bending. MTSS2 is highly expressed in the central nervous system (CNS) and appears to be involved in activity-dependent synaptic plasticity. Variants in MTSS2 have not yet been associated with a human phenotype in OMIM. Here we report five individuals with the same heterozygous de novo variant in MTSS2 (GenBank: NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing. The individuals present with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms. Immunoblots of fibroblasts from two affected individuals revealed that the …

Peripheral Blood Monocytes As A Therapeutic Target For Marrow Stromal Cells In Stroke Patients, Nikunj Satani, Kaushik Parsha, Courtney Davis, Adrian Gee, Scott D Olson, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: Systemic administration of marrow stromal cells

METHODS: Peripheral blood from stroke patients was collected at 5-7 days (

RESULTS: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared …

Allostatic Load Predicts Racial Disparities In Intracerebral Hemorrhage Cognitive Outcomes, Jennifer Harris, Amelia Boehme, Luisa Chan, Harmon Moats, Rachelle Dugue, Chigozirim Izeogu, Marykay A Pavol, Imama A Naqvi, Olajide Williams, Randolph S Marshall

Faculty, Staff and Student Publications

A large portion of stroke disparities remains unexplained, even after adjusting for demographic, comorbidity, and health care access variables. There is a critical need to close this knowledge gap by investigating novel factors that may contribute to stroke disparities. Allostatic load (AL) is the lifetime adverse physiologic impact of needing to adjust to socially structured stressors such as racism. AL has been shown to increase health vulnerability and worsen outcomes in marginalized populations. We sought to assess the differential impact of AL on cognitive outcomes post intracerebral hemorrhage (ICH) across race-ethnicity. The Intracerebral Hemorrhage Outcomes Project (ICHOP) prospectively collected data …

Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Kamran Hessami, Amir Hossein Norooznezhad, Sonia Monteiro, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

IMPORTANCE: Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

OBJECTIVES: To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

DATA SOURCES: PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

STUDY SELECTION: Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic …

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.