Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), 2018 University of Massachusetts Medical School
Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu
GSBS Dissertations and Theses
A list of genes have been identified to carry mutations causing familial ALS such as SOD1, TARDBP, C9orf72. But for sporadic ALS, which is 90% of all ALS cases, the underlying genetic variants are still largely unknown. There are multiple genome-wide association study (GWAS) for sporadic ALS, but usually a large number nominated SNP can hardly be replicated in larger cohort analysis. Also majority of GWAS SNP lie within noncoding region of genome, imposing a huge challenge to study their biological role in ALS pathology. With the rapid development of next-generation sequencing technology, we are able to sequence exome and ...
A Rare Case Of Enhancing Anterior Interhemispheric Racemose Neurocysticercosis With Foci Of Calcification And Direct Parenchymal Extension, 2018 JSS Medical College Hospital, JSS University, Mysore
A Rare Case Of Enhancing Anterior Interhemispheric Racemose Neurocysticercosis With Foci Of Calcification And Direct Parenchymal Extension, Anupama Chandrappa, Rajesh Raman, Suchetha Satish
Journal of Global Radiology
Neurocysticercosis (NCC) refers to the central nervous system (CNS) infestation of the larvae of pork tapeworm Taenia solium. It is endemic in Central and South America, Asia and Africa. It most commonly presents as intraparenchymal subcentimetric ring enhancing lesions of variable ages (or size and duration) with surrounding vasogenic edema. The lesions calcify with time. Rarely, NCC can occur in extraparenchymal locations, within the subarachnoid space and ventricles. At these locations it is usually seen as a proliferative lobulated cystic mass without a scolex which is termed racemose neurocysticercosis. Racemose cysticerci do not show calcification, scolex, or enhancement.
We report ...
Pilot Study To Assess Visualization And Therapy Of Inflammatory Mechanisms After Vessel Reopening In A Mouse Stroke Model, 2018 Klinikum rechts der Isar der Technischen Universität München
Pilot Study To Assess Visualization And Therapy Of Inflammatory Mechanisms After Vessel Reopening In A Mouse Stroke Model, Ebba Beller, Laura Reuter, Anne Kluge, Christine Preibisch, Ute Lindauer, Alexei A. Bogdanov Jr., Friederike Lammer, Claire Delbridge, Kaspar Matiasek, Benedikt J. Schwaiger, Tobias Boeckh-Behrens, Claus Zimmer, Alexandra S. Gersing
Radiology Publications and Presentations
After reperfusion therapy in stroke patients secondary inflammatory processes may increase cerebral damage. In this pilot study, effects of anti-inflammatory therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion-weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted images with and without Bis-5HT-DTPA administration were obtained 24 hours after MCAO. Neutrophils, Myeloperoxidase-positive-(MPO+)-cells and microglia, including M1 and M2 phenotypes, were assessed immunohistochemically. Treatment with tacrolimus led to significantly smaller apparent diffusion ...
Development Of A Pet Radioligand For Potassium Channels To Image Cns Demyelination, 2018 George Washington University
Development Of A Pet Radioligand For Potassium Channels To Image Cns Demyelination, Pedro Brugarolas, Jorge Sanchez-Rodriguez, Hsiu-Ming Tsai, Falguni Basuli, Shih-Hsun Cheng, Robert H. Miller, +Several Additional Authors
Anatomy and Regenerative Biology Faculty Publications
Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties ...
Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, 2018 Touro University California
Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, Shankar J. Chinta, Georgia Woods, Marco Demaria, Anand Rane, Ying Zou, Amanda Mcquade, David T. Madden
College of Pharmacy (TUC) Publications and Research
Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects ...
Ccl11 As A Biomarker For The In Vivo Diagnosis Of Chronic Traumatic Encephalopathy, 2018 Claremont McKenna College
Ccl11 As A Biomarker For The In Vivo Diagnosis Of Chronic Traumatic Encephalopathy, Robert Weissenfels
CMC Senior Theses
Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known ...
Why West? Comparisons Of Clinical, Genetic And Molecular Features Of Infants With And Without Spasms., 2018 George Washington University
Why West? Comparisons Of Clinical, Genetic And Molecular Features Of Infants With And Without Spasms., Anne T Berg, Samya Chakravorty, Sookyong Koh, Zachary M Grinspan, Renée A Shellhaas, William D Gaillard, +Several Additional Authors
Neurology Faculty Publications
Infantile spasms are the defining seizures of West syndrome, a severe form of early life epilepsy with poorly-understood pathophysiology. We present a novel comparative analysis of infants with spasms versus other seizure-types and identify clinical, etiological, and molecular-genetic factors preferentially predisposing to spasms. We compared ages, clinical etiologies, and associated-genes between spasms and non-spasms groups in a multicenter cohort of 509 infants (
Structural Insights Into The Potency Of Sk Channel Positive Modulators, 2017 Chapman University
Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2 ...
X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., 2017 George Washington University
X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors
Neurology Faculty Publications
An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor ...
Effect Of Src Kinase Inhibition On Cytochrome C, Smac/Diablo And Apoptosis Inducing Factor (Aif) Following Cerebral Hypoxia-Ischemia In Newborn Piglets., Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis, Maria Delivoria-Papadopoulos
Pediatrics Faculty Publications
We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E and biochemical enzyme assays to determine the role of Src kinase on ...
Unexpected Dual Task Benefits On Cycling In Parkinson Disease And Healthy Adults: A Neuro-Behavioral Model, 2017 University of Florida
Unexpected Dual Task Benefits On Cycling In Parkinson Disease And Healthy Adults: A Neuro-Behavioral Model, Lori J. P. Altmann, Elizabeth L. Stegemoller, Audrey A. Hazamy, Jonathan P. Wilson, Michael S. Okun, Nikolaus R. Mcfarland, Aparna W. Shukla, Chris J. Hass
Elizabeth L. Stegemoller
Background When performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson’s disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs. Methods Twenty-eight participants with Parkinson’s disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a ...
Brain Imaging In Older Patients With Delirium, 2017 Aurora St. Luke's Medical Center
Brain Imaging In Older Patients With Delirium, Laila M. Hasan, Ariba Khan, Maharaj Singh, Michael L. Malone
Journal of Patient-Centered Research and Reviews
Background: Delirium is a common, serious and costly condition in older patients admitted to the hospital. This study describes the prevalence and results of brain imaging among a cohort of older hospitalized patients with and without delirium.
Purpose: Investigate the frequency and results of brain imaging in older patients with delirium as compared to those without delirium.
Methods: This was a cross-sectional study. Data were collected on hospitalized patients age 65 years or older who were admitted to 3 hospitals in Milwaukee, Wisconsin, during a 1-month period in the fall of 2013. Subjects were tested for delirium via the “Confusion ...
Phytic Acid Protects Against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis In Normal And Iron Excess Conditions In A Cell Culturemodel, 2017 Shanghai University of Traditional Chinese Medicine and Pharmacology
Phytic Acid Protects Against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis In Normal And Iron Excess Conditions In A Cell Culturemodel, Qi Xu, Anumantha G. Kanthasamy, Manju B. Reddy
Manju B. Reddy
Iron may play an important role in Parkinson’s disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; P < .001) and 30 μmol/L IP6 pretreatment decreased it by 38% (P < .05). Similarly, a 63% protection (P < .001) against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in ...
A General Neurologist's Perspective On The Urgent Need To Apply Resilience Thinking To The Prevention And Treatment Of Alzheimer's Disease, 2017 University of Massachusetts Medical School
A General Neurologist's Perspective On The Urgent Need To Apply Resilience Thinking To The Prevention And Treatment Of Alzheimer's Disease, Grazyna Pomorska, Judith K. Ockene
Open Access Articles
The goal of this article was to look at the problem of Alzheimer's disease (AD) through the lens of a socioecological resilience-thinking framework to help expand our view of the prevention and treatment of AD. This serious and complex public health problem requires a holistic systems approach. We present the view that resilience thinking, a theoretical framework that offers multidisciplinary approaches in ecology and natural resource management to solve environmental problems, can be applied to the prevention and treatment of AD. Resilience thinking explains a natural process that occurs in all complex systems in response to stressful challenges. The ...
Medical Therapies For Motor Symptoms In Parkinson’S Disease, 2017 Marshall University Joan C. Edwards School of Medicine
Medical Therapies For Motor Symptoms In Parkinson’S Disease, Conrad Musey, Vikram Shivkumar
Marshall Journal of Medicine
Parkinson’s Disease is the second most common neurodegenerative disorder in the aging population. It is associated with progressive loss of nigrostriatal dopaminergic neurons. Parkinsonism is a clinical syndrome that consists of motor and non-motor symptoms. It has been well described that many if not all of these deficits are associated with abnormalities related to the neurotransmitter Dopamine. This review is intended for primary care physicians who often establish the diagnosis and initiate Parkinson’s treatments. One challenge faced by the primary care physician is to decide the appropriate medication and starting dose. Often medications are used at very low ...
Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., 2017 George Washington University
Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.
Neurology Faculty Publications
OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.
METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.
RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a ...
Rna Sequencing And Proteomics Approaches Reveal Novel Deficits In The Cortex Of Mecp2-Deficient Mice, A Model For Rett Syndrome, 2017 University of Alabama, Birmingham
Rna Sequencing And Proteomics Approaches Reveal Novel Deficits In The Cortex Of Mecp2-Deficient Mice, A Model For Rett Syndrome, Natasha L. Pacheco, Michael R. Heaven, Leanne M. Holt, David K. Crossman, Kristin J. Boggio, Scott A. Shaffer, Daniel L. Flint, Michelle L. Olsen
Open Access Articles
BACKGROUND: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. Much of our understanding of MeCP2 function is derived from transcriptomic studies with the general assumption that alterations in the transcriptome correlate with proteomic changes. Advances in mass spectrometry-based proteomics have facilitated recent interest in the examination of global protein expression to better understand the biology between transcriptional and translational regulation.
METHODS: We therefore performed the first comprehensive transcriptome-proteome comparison in a RTT mouse model to elucidate RTT pathophysiology, identify potential therapeutic targets, and further our understanding of MeCP2 function. The whole cortex ...
Mental Illness And The Grace Of God, 2017 Cedarville University
Mental Illness And The Grace Of God, Laura K. Sjoquist
Bioethics in Faith and Practice
This paper will attempt to address God's grace towards those with mental illnesses. It also attempts to provide direction in response to historical church views towards this population. Through scripture, this paper seeks to emphasize the importance of seeing a person as more than what they physically appear capable of - seeing people through God's eyes.
Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, 2017 University of Alberta
Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas
Pharmacy Faculty Articles and Research
Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.
Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) were ...
Will Vestibulo-Ocular Reflex And Balance Rehabilitation Reduce Visual Deficits & Improve Stability Of A Patient With Multiple Sclerosis?, Natalie Hunt, Jennifer Kiggins
Sacred Heart University Scholar
Context: Identification of rehabilitation exercises to decrease symptomology in a patient with Multiple Sclerosis (MS) is necessary for enhancing quality of life. Various vestibulo-ocular reflex (VOR) rehabilitation exercises can help patients adapt to balance problems. Currently, no researcher has utilized the VSR™ Sport and inVision™ systems by NeuroCom® for rehabilitation among patients with MS.
Objective: The purpose of the study was to create a rehabilitation protocol incorporating VOR and balance exercises to decrease visual deficits and improve stability in a patient with MS. This study will examine the effects of rehabilitation and determine if scores improve from baseline testing.