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Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour 2019 American University of Health Sciences

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results ...


Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio 2019 Chapman University

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There ...


Huntingtin Associates With The Actin Cytoskeleton And Alpha-Actinin Isoforms To Influence Stimulus Dependent Morphology Changes, Adelaide Tousley, Maria Iuliano, Elizabeth Weisman, Ellen Sapp, Heather Richardson, Petr Vodicka, Jonathan Alexander, Neil Aronin, Marian DiFiglia, Kimberly B. Kegel-Gleason 2019 Massachusetts General Hospital

Huntingtin Associates With The Actin Cytoskeleton And Alpha-Actinin Isoforms To Influence Stimulus Dependent Morphology Changes, Adelaide Tousley, Maria Iuliano, Elizabeth Weisman, Ellen Sapp, Heather Richardson, Petr Vodicka, Jonathan Alexander, Neil Aronin, Marian Difiglia, Kimberly B. Kegel-Gleason

Open Access Articles

One response of cells to growth factor stimulus involves changes in morphology driven by the actin cytoskeleton and actin associated proteins which regulate functions such as cell adhesion, motility and in neurons, synaptic plasticity. Previous studies suggest that Huntingtin may be involved in regulating morphology however, there has been limited evidence linking endogenous Huntingtin localization or function with cytoplasmic actin in cells. We found that depletion of Huntingtin in human fibroblasts reduced adhesion and altered morphology and these phenotypes were made worse with growth factor stimulation, whereas the presence of the Huntington's Disease mutation inhibited growth factor induced changes ...


Early Dexamethasone Administration In Adults With Suspected Meningitis Lowers Morbidity And Mortality, Dana Siegel 2019 Wayne State University

Early Dexamethasone Administration In Adults With Suspected Meningitis Lowers Morbidity And Mortality, Dana Siegel

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of de Gans J, van de Beek D, Investigators EDiABMS. Dexamethasone in adults with bacterial meningitis. New Eng J Med. 2002;347(20):1549-1556. doi: 10.1056/NEJMoa021334.


Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan 2019 The Graduate Center, City University of New York

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

All Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that ...


Randomized Trial Of L-Serine In Patients With Hereditary Sensory And Autonomic Neuropathy Type 1, Vera Fridman, Saranya Suriyanarayanan, Peter Novak, William David, Eric A. Macklin, Diane McKenna-Yasek, Kailey Walsh, Razina Aziz-Bose, Anne Louise Oaklander, Robert H. Brown Jr., Thorsten Hornemann, Florian Eichler 2019 Harvard Medical School

Randomized Trial Of L-Serine In Patients With Hereditary Sensory And Autonomic Neuropathy Type 1, Vera Fridman, Saranya Suriyanarayanan, Peter Novak, William David, Eric A. Macklin, Diane Mckenna-Yasek, Kailey Walsh, Razina Aziz-Bose, Anne Louise Oaklander, Robert H. Brown Jr., Thorsten Hornemann, Florian Eichler

Open Access Articles

OBJECTIVE: To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1).

METHODS: In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events.

RESULTS: Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 ...


Trisomy Silencing By Xist Normalizes Down Syndrome Cell Pathogenesis Demonstrated For Hematopoietic Defects In Vitro, Jen-Chieh Chiang, Jun Jiang, Peter E. Newburger, Jeanne B. Lawrence 2018 University of Massachusetts Medical School

Trisomy Silencing By Xist Normalizes Down Syndrome Cell Pathogenesis Demonstrated For Hematopoietic Defects In Vitro, Jen-Chieh Chiang, Jun Jiang, Peter E. Newburger, Jeanne B. Lawrence

Open Access Articles

We previously demonstrated that an integrated XIST transgene can broadly repress one chromosome 21 in Down syndrome (DS) pluripotent cells. Here we address whether trisomy-silencing can normalize cell function and development sufficiently to correct cell pathogenesis, tested in an in vitro model of human fetal hematopoiesis, for which DS cellular phenotypes are best known. XIST induction in four transgenic clones reproducibly corrected over-production of megakaryocytes and erythrocytes, key to DS myeloproliferative disorder and leukemia. A contrasting increase in neural stem and iPS cells shows cell-type specificity, supporting this approach successfully rebalances the hematopoietic developmental program. Given this, we next used ...


Reluctance Of Adolescents With Cerebral Palsy To Participate In An Online Intervention On Self-Management: Lessons Learned From A Randomized Control Trial, Cynthia T. Thompson 2018 University of Massachusetts Medical School

Reluctance Of Adolescents With Cerebral Palsy To Participate In An Online Intervention On Self-Management: Lessons Learned From A Randomized Control Trial, Cynthia T. Thompson

Graduate School of Nursing Dissertations

Purpose: Assess the effectiveness of an online intervention to encourage self-management in adolescents with cerebral palsy (CP).

Specific Aims: (a) assess effectiveness of an online intervention to promote readiness for self-management in adolescents with CP, (b) describe health literacy and associations with readiness to assume self-management, and (c) evaluate adolescents’ exposure to the online intervention.

Hypotheses: (a) intervention subjects would demonstrate improvement in self-management, and (b) subjects with higher health literacy would demonstrate higher self-management capabilities.

Framework: Transtheoretical Model of Health Behavior Change

Design: Randomized control trial, performed in a multidisciplinary CP clinic at a university based children’s hospital ...


Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem 2018 The Univesity of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

UT GSBS Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly ...


Protein Aggregates And Polyglutamine Tracts In Neurodegenerative Disease, John Mack 2018 Liberty University

Protein Aggregates And Polyglutamine Tracts In Neurodegenerative Disease, John Mack

Senior Honors Theses

The incidence of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and other Polyglutamine Diseases is projected to dramatically increase throughout the developed world, and yet the pathology of these diseases remains poorly understood. One pathway that these neurodegenerative diseases share is the accumulation of pathologic proteins which are not only harmful in their soluble form but may go on to form toxic aggregates. In many cases, a consensus has yet to be reached concerning the mechanism for protein aggregation. Therefore, the exploration of the roles of these proteins and their possible mechanisms, along with ...


The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen 2018 The University of Western Ontario

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the ...


Experiences Of Persons With Parkinson’S Disease Engaged In Group Therapeutic Singing, Elizabeth L. Stegemoller, Tera R. Hurt, Margaret C. Shirley, Randie D. Camp, Chrishelda W. Green, Jenna C. Pattee, Ebony Williams 2018 Iowa State University

Experiences Of Persons With Parkinson’S Disease Engaged In Group Therapeutic Singing, Elizabeth L. Stegemoller, Tera R. Hurt, Margaret C. Shirley, Randie D. Camp, Chrishelda W. Green, Jenna C. Pattee, Ebony Williams

Elizabeth L. Stegemoller

Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder that leads to altered neural control of movement, including the control of voice, respiration, and swallowing. There is a prevalent need to provide therapy for voice, respiration, and swallowing difficulties because current pharmacological and surgical treatments do not effectively treat these impairments. Previous research has demonstrated that singing may be a treatment option to target voice, respiratory, and swallowing impairments, as well as quality of life. However, participants’ perspectives related to reasons for enrolling and engaging in programs as well as evaluation of singing programs have been neglected.

Objective The ...


Who Did It?: A Review On The Possible Causes Of Multiple Sclerosis, Mia DiFrancesco 2018 Duquesne University

Who Did It?: A Review On The Possible Causes Of Multiple Sclerosis, Mia Difrancesco

D.U.Quark

Multiple Sclerosis (MS) is an incurable autoimmune disorder that attacks the myelin sheath surrounding nerve cells. Steady demyelination of these cells over time results in painful inflammation and reduced mobility. Genetic abnormalities could be responsible for the onset of this disease. Chromosomal mutations found in MS patients as well as environmental factors influencing the expression of certain genes will be analyzed in this review. Moreover, treatments regulating gene expression in MS patients will be discussed. Further genetic research would not only provide scientists and medical professionals with a deeper understanding of MS and other autoimmune disorders, but also lead to ...


Chd3 Helicase Domain Mutations Cause A Neurodevelopmental Syndrome With Macrocephaly And Impaired Speech And Language, Lot Snijders Blok, Inderneel Sahai, Philippe M. Campeau 2018 Radboud University Medical Center

Chd3 Helicase Domain Mutations Cause A Neurodevelopmental Syndrome With Macrocephaly And Impaired Speech And Language, Lot Snijders Blok, Inderneel Sahai, Philippe M. Campeau

Pediatric Publications and Presentations

Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates ...


Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19 2018 Illinois Mathematics and Science Academy

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.


Defective Cortex Glia Plasma Membrane Structure Underlies Light-Induced Epilepsy In Cpes Mutants, Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya 2018 National Cancer Institute

Defective Cortex Glia Plasma Membrane Structure Underlies Light-Induced Epilepsy In Cpes Mutants, Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya

Open Access Articles

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and ...


Sumo-Targeted Ubiquitin Ligases (Stubls) Reduce The Toxicity And Abnormal Transcriptional Activity Associated With A Mutant, Aggregation-Prone Fragment Of Huntingtin, Kentaro Ohkuni, Nagesh Pasupala, Jennifer Peek, Grace Lauren Holloway, Gloria D. Sclar, Reuben Levy-Myers, Richard E. Baker, Munira A. Basrai, Oliver Kerscher 2018 National Institutes of Health

Sumo-Targeted Ubiquitin Ligases (Stubls) Reduce The Toxicity And Abnormal Transcriptional Activity Associated With A Mutant, Aggregation-Prone Fragment Of Huntingtin, Kentaro Ohkuni, Nagesh Pasupala, Jennifer Peek, Grace Lauren Holloway, Gloria D. Sclar, Reuben Levy-Myers, Richard E. Baker, Munira A. Basrai, Oliver Kerscher

Open Access Articles

Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin (Htt), the causative agent of HD. We demonstrate that expression of an aggregation-prone Htt construct with 103 glutamine residues (103Q), but not the non-expanded form (25Q), results in severe growth defects in slx5Delta and slx8Delta cells. Since Slx5 is a nuclear protein and because Htt expression affects gene transcription, we assessed ...


Nuclear Localization Of Huntingtin Mrna Is Specific To Cells Of Neuronal Origin, Marie C. Didiot, Chantal M. Ferguson, Socheata Ly, Andrew H. Coles, Abigail O. Smith, Alicia A. Bicknell, Lauren M. Hall, Ellen Sapp, Dimas Echeverria, Athma A. Pai, Marian DiFiglia, Melissa J. Moore, Lawrence J. Hayward, Neil Aronin, Anastasia Khvorova 2018 University of Massachusetts Medical School

Nuclear Localization Of Huntingtin Mrna Is Specific To Cells Of Neuronal Origin, Marie C. Didiot, Chantal M. Ferguson, Socheata Ly, Andrew H. Coles, Abigail O. Smith, Alicia A. Bicknell, Lauren M. Hall, Ellen Sapp, Dimas Echeverria, Athma A. Pai, Marian Difiglia, Melissa J. Moore, Lawrence J. Hayward, Neil Aronin, Anastasia Khvorova

RNA Therapeutics Institute Publications

Huntington's disease (HD) is a monogenic neurodegenerative disorder representing an ideal candidate for gene silencing with oligonucleotide therapeutics (i.e., antisense oligonucleotides [ASOs] and small interfering RNAs [siRNAs]). Using an ultra-sensitive branched fluorescence in situ hybridization (FISH) method, we show that approximately 50% of wild-type HTT mRNA localizes to the nucleus and that its nuclear localization is observed only in neuronal cells. In mouse brain sections, we detect Htt mRNA predominantly in neurons, with a wide range of Htt foci observed per cell. We further show that siRNAs and ASOs efficiently eliminate cytoplasmic HTT mRNA and HTT protein, but ...


Breastfeeding History And Risk Of Stroke Among Parous Postmenopausal Women In The Women's Health Initiative, Lisette T. Jacobson, Erinn M. Hade, Tracie C. Collins, Karen L. Margolis, Molly E. Waring, Linda V. Van Horn, Brian Silver, Maryam Sattari, Chloe E. Bird, Kim Kimminau, Karen Wambach, Marcia L. Stefanick 2018 University of Kansas

Breastfeeding History And Risk Of Stroke Among Parous Postmenopausal Women In The Women's Health Initiative, Lisette T. Jacobson, Erinn M. Hade, Tracie C. Collins, Karen L. Margolis, Molly E. Waring, Linda V. Van Horn, Brian Silver, Maryam Sattari, Chloe E. Bird, Kim Kimminau, Karen Wambach, Marcia L. Stefanick

Open Access Articles

Background: Stroke is the third leading cause of death among US Hispanic and non-Hispanic black women aged 65 and older. One factor that may protect against stroke is breastfeeding. Few studies have assessed the association between breastfeeding and stroke and whether this association differs by race and ethnicity.

Methods and Results: Data were taken from the Women's Health Initiative Observational Study with follow-up through 2010; adjusted hazard ratios for stroke subsequent to childbirth were estimated with Cox regression models accounting for left and right censoring, overall and stratified by race/ethnicity. Of the 80 191 parous women in the ...


Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic 2018 Karolinska Institutet, Sweden

Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic

Epidemiology Faculty Publications

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.

Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).

Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.

Results: We observed significant methylation differences in ...


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