Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, 2021 West Virginia University
Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish
Graduate Theses, Dissertations, and Problem Reports
Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...
Geriatrics In Clinical Practice And Beyond: Brain Health, The Sixth Vital Sign?, Nannette Hoffman
HCA Healthcare Journal of Medicine
Brain health in middle age and geriatric patients will take on greater importance for health care practitioners in our aging society. This article discusses various approaches clinicians can use for their patients to promote and improve brain health. These are generally the same lifestyle adoptions for cerebrovascular disease and cardiovascular disease prevention: weight management, exercise, and blood pressure and cholesterol lowering. Social stimulation and cognitive activities may also be important for the elderly.
A Case Of Disseminated Nocardia Beijingensis In An Immunocompetent Patient, Manifesting As Subcutaneous And Cns Nocardiosis., Scott Cathcart, Patricia Stogsdill, Rebecca Bell
Journal of Maine Medical Center
Nocardiosis is an uncommon infection, typically encountered in immunocompromised patients. With only 5 cases reported thus far in the United States, we present a case of disseminated Nocardia beijingensis in an immunocompetent patient, involving the lung, subcutaneous tissue, and CNS.
A 60-year-old immunocompetent male with no significant medical history presents to our institution after a complicated medical course, beginning with vague respiratory complaints. Initial work-up revealed a large right upper lung mass of unclear etiology. A month later he had a syncopal episode followed by the development of focal neurologic deficits.
Main Diagnoses, Therapeutics Interventions, and Outcomes ...
Failure To Thrive - An Overlooked Manifestation Of Kmt2b-Related Dystonia: A Case Presentation., 2020 Children's Mercy Hospital
Failure To Thrive - An Overlooked Manifestation Of Kmt2b-Related Dystonia: A Case Presentation., Andrew Ng, Serena Galosi, Lisa Salz, Terence Wong, Caitlin Schwager, Shivarajan Amudhavalli, Rose N. Gelineau-Morel, Shimul Chowdhury, Rady Children’S Institute For Genomic Medicine Investigators, Jennifer Friedman
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel KMT2B mutation with several members with failure to thrive to highlight this non-neurologic, but consequential impact of mutation in this gene.
CASE PRESENTATION: We present a case of a 15-year old female who was admitted and evaluated for failure to thrive. On exam, she had severe speech dysfluency, limited ability to protrude the ...
Cerebrovascular Events In Covid-19 Patients, 2020 St. Vincent Hospital
Cerebrovascular Events In Covid-19 Patients, Ajay Kumar Mishra, Kamal Kant Sahu, Anu Anna George, Jennifer B. Sargent, Amos Lal
COVID-19 Publications by UMMS Authors
Neurological manifestations in patients with COVID-19 are more frequently being reported. Cerebrovascular events have been reported in around 3% of patients. In this review we summarize the published literature on cerebrovascular events in patients with COVID-19 as available on the PubMed database. So far, 3 studies have reported cerebrovascular events. Cerebrovascular events were identified on screening patients with decreased consciousness or in the presence of focal neurological deficits. These events were common in elderly, critically ill patients and in patients with prior cardio-cerebrovascular comorbidities. The diagnosis of cerebrovascular events was confirmed with computed tomography of the brain in most studies ...
Longitudinal Biomarkers In Amyotrophic Lateral Sclerosis, 2020 Denali Therapeutics
Longitudinal Biomarkers In Amyotrophic Lateral Sclerosis, Fen Huang, Yuda Zhu, Jennifer Hsiao-Nakamoto, Xinyan Tang, Jason C. Dugas, Miriam Moscovitch-Lopatin, Jonathan D. Glass, Robert H. Brown Jr., Shafeeq S. Ladha, David Lacomis, Jeffrey M. Harris, Kimberly Scearce-Levie, Carole Ho, Robert Bowser, James D. Berry
Open Access Articles
OBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.
METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from > /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and ...
Immediate And Long-Term Consequences Of Covid-19 Infections For The Development Of Neurological Disease, 2020 University of Massachusetts Medical School
Immediate And Long-Term Consequences Of Covid-19 Infections For The Development Of Neurological Disease, Michael T. Heneka, Douglas T. Golenbock, Eicke Latz, Dave Morgan, Robert H. Brown Jr.
COVID-19 Publications by UMMS Authors
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding ...
Supplementary Material To The Manuscript Titled: Mobile Phone Sensors Can Discern Medication-Related Gait Quality Changes In Parkinson's Patients In A Real-World Setting, Niklas König Ignasiak, Albert Pierce, Vincent Berardi, Wilford K. Eiteman-Pang, Cyril Rakovski
Physical Therapy Faculty Data Sets
This file contains the data that was used to classify high and low quality gait patterns in patients with Parkinson's disease. Acceleration and gyroscope data was recorded with a conventional smartphone in a real-world environment. High (i.e. ON medication) and low (i.e. OFF medication) quality labels were given by a human observer according to medication intake times.
Plcg2 Protective Variant P.P522r Modulates Tau Pathology And Disease Progression In Patients With Mild Cognitive Impairment, Luca Kleineidam, Michael T. Heneka, Alfredo Ramirez
Open Access Articles
A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-gamma2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Abeta1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate ...
Kcnq2 Localization In The Brainstem, 2020 University of Connecticut
Kcnq2 Localization In The Brainstem, Christina Valera
Honors Scholar Theses
KCNQ2 channels are potassium channels that serve to control neuronal excitability. Loss of function mutations in these channels are known to cause various forms of epilepsy. Recently, KCNQ2 R201C and R201H gain of function mutations have been shown to exhibit an exaggerated startle response and other unique phenotypes uncharacteristic of epilepsy. These phenotypes resemble hyperekplexia, a condition in which glycine neurotransmission in the spinal cord and brainstem is affected. While KCNQ2 has widespread localization throughout the brain, its presence in the brainstem remains unknown. We used immunostaining to determine the localization of KCNQ2 in the vagus nerve and hypoglossal nerve ...
Trpv4 Disrupts Mitochondrial Transport And Causes Axonal Degeneration Via A Camkii-Dependent Elevation Of Intracellular Ca(2), Brian M. Woolums, Kendra Takle, Yang Xiang
University of Massachusetts Medical School Faculty Publications
The cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here, we show that in vivo expression of a neuropathy-causing TRPV4 mutant (TRPV4(R269C)) causes dose-dependent neuronal dysfunction and axonal degeneration, which are rescued by genetic or pharmacological blockade of TRPV4 channel activity. TRPV4(R269C) triggers increased intracellular Ca(2+) through a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated mechanism, and CaMKII inhibition prevents both increased intracellular Ca(2+) and neurotoxicity in Drosophila and cultured primary mouse neurons. Importantly ...
Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas
Honors Scholar Theses
Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic ...
The Partial Immersion Aquatic Approach Using Adjustable Weight Bearing To Improve Posture And Sitting Balance Adaptation For Children With Severe Cerebral Palsy, Niv Shelef
International Journal of Aquatic Research and Education
The innovative ‟Partial Immersion” Aquatic Therapy Approach was developed to enhance balance and posture during sitting adaptation for children with severe cerebral palsy who exhibit deficiency in those skills on land. Stable balance during sitting posture is one of the preconditions for hands function in activities of daily living. Aquatic skills learned during aquatic therapy were then transferred to a land environment. Therapy included the use of a treatment chair that enabled adjustable weight bearing in a series of 30 mm steps. A mixed-methods design employing a multiple case study approach (n=5) including quantitative and qualitative methods investigated the ...
Fmrp Links Optimal Codons To Mrna Stability In Neurons, 2020 University of Massachusetts Medical School
Fmrp Links Optimal Codons To Mrna Stability In Neurons, Huan Shu, Elisa Donnard, Botao Liu, Ruijia Wang, Joel D. Richter
University of Massachusetts Medical School Faculty Publications
Fragile X syndrome (FXS) is caused by inactivation of the FMR1 gene and loss of encoded FMRP, an RNA binding protein that represses translation of some of its target transcripts. Here we use ribosome profiling and RNA-seq to investigate the dysregulation of translation in the mouse brain cortex. We find that most changes in ribosome occupancy on hundreds of mRNAs are largely driven by dysregulation in transcript abundance. Many downregulated mRNAs, which are mostly responsible for neuronal and synaptic functions, are highly enriched for FMRP binding targets. RNA metabolic labeling demonstrates that in FMRP-deficient cortical neurons, mRNA downregulation is caused ...
The Current Neuroscientific Understanding Of Alzheimer's Disease, 2020 University of Tennessee, Knoxville
The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes
Pursuit - The Journal of Undergraduate Research at the University of Tennessee
Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most ...
Functional Analysis Of A Critical Glycine (Glycine 12) In Beta-Type Connexins Of Human Skin, 2020 State University of New York College at Buffalo - Buffalo State College
Functional Analysis Of A Critical Glycine (Glycine 12) In Beta-Type Connexins Of Human Skin, Rasheed Bailey
At least five beta-type connexins are expressed in various layers of the skin (Cx26, Cx30, Cx30.3, Cx31, and Cx32) and all include a glycine residue at position 12. Glycine12 (G12) is located about halfway through the cytoplasmic amino terminus and has been the focus of several studies related to connexin diseases and gap junction channel structure. The importance of this residue is evident in the severity and diversity of diseases associated with amino acid substitutions at G12 including hereditary forms of skin disease, deafness and neuropathy. This study uses bioinformatic analysis in combination with mutational analysis and electrophysiology to ...
A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham
Undergraduate Honors Theses
Understanding the genes and mechanisms that regulate the highly important process of neurogenesis in the developing nervous system is crucial to uncovering why disease arises when this system is disrupted. Neural progenitor cells and their multipotent nature allow for the growth of a large pool of stem cells in the early stages of development, but the signal that leads these cells to the irreversible fate of becoming a neuron is unclear. The gene matr3 has been implicated in having a role in the maintenance of undifferentiated neural stem cells but its role needs further investigation to fully reveal how its ...
Phenotypic Variability Among Patients With D4z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy, 2020 University Federico II
Phenotypic Variability Among Patients With D4z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy, Lucia Ruggiero, Rossella Tupler
Open Access Articles
Importance: Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disorder, associated with the deletion of tandemly arrayed D4Z4 repetitive elements. The extensive use of molecular analysis of the D4Z4 locus for FSHD diagnosis has revealed wide clinical variability, suggesting that subgroups of patients exist among carriers of the D4Z4 reduced allele (DRA).
Objective: To investigate the clinical expression of FSHD in the genetic subgroup of carriers of a DRA with 7 to 8 repeat units (RUs).
Design, Setting, and Participants: This multicenter cross-sectional study included 422 carriers of DRA with 7 to 8 RUs (187 unrelated probands and 235 ...
Optical Clearing Reveals Tnbs-Induced Morphological Changes Of Vglut2-Positive Nerve Endings In The Colorectum, 2020 University of Connecticut
Optical Clearing Reveals Tnbs-Induced Morphological Changes Of Vglut2-Positive Nerve Endings In The Colorectum, Shivam Patel
Honors Scholar Theses
Sensitization of colorectal afferents and colorectal hypersensitivity have been observed in a mouse model of post-infectious irritable bowel syndrome via intracolonic treatment of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In this study, we investigated the distribution and morphology of microscopic colorectal afferent endings before and after intracolonic treatment of TNBS. We genetically labeled predominantly extrinsic colorectal afferents using the vesicular glutamate transporter type 2 (VGLUT2) promoter. Then, we used an optical tissue clearing method of whole-mount colorectum to image labeled VGLUT2-nerve endings that are otherwise obscured in untreated samples. We used vector path tracing to quantify the density and degree of ...
An Atypical Presentation Of Neuroleptic Malignant Syndrome, 2020 HCA Healthcare
An Atypical Presentation Of Neuroleptic Malignant Syndrome, Rudy Forte Md, Shiwani Kamath Md, Debra Angelo Md, Johnathan Frunzi Md
West Florida Division Virtual Research Day
Neuroleptic Malignant Syndrome (NMS) is a rare, but potentially life threatening condition associated with dopamine blockade, particularly first-generation antipsychotics. The complex pathophysiology of NMS remains somewhat unclear and debatable as the symptoms are not fully explained by dopamine blockade alone.1 D2 dopamine receptor antagonism remains responsible for most cases of NMS, however a few cases have been reported in which little to no D2 blockade activity was present.1
This poster is about an atypical presentation of NMS.