Nervous System Diseases Commons^™

Further Analyses Of The Safety Of Verubecestat In The Phase 3 Epoch Trial Of Mild-To-Moderate Alzheimer’S Disease, Michael F. Egan, Yuki Mukai, Tiffini Voss, James Kost, Julie Stone, Christine Furtek, Erin Mahoney, Jeffrey L. Cummings, Pierre N. Tariot, Paul S. Aisen, Bruno Vellas, Christopher Lines, David Michaelson

Integrated Health Sciences Faculty Research

Background: Verubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH. Methods: EPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically. The trial was terminated due to futility close to its scheduled completion. Of 1957 participants who were randomized and took treatment, 652 were assigned to verubecestat 12 mg, 652 …

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Multiple Sclerosis Pathophysiology, Carolyn Ricketts

Nursing Student Class Projects (Formerly MSN)

Abstract

Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by inflammation in the central nervous system and demyelination of the white matter in the brain and spinal cord, leading to lesions and axonal damage, possibly followed by relapse. It is a progressively debilitating disease with a variety of symptoms that mimic other diseases, such as blurred vision, nerve pain, fatigue, weakness, paresthesia, and unsteady gait. It occurs more frequently further from the equator. The pathophysiology of MS is unknown. Several new research theories are emerging which include innate and adaptive immunity playing a role (TH1 and TH17 specifically), infection …

‘Dancing At The Vatican,’ About Huntington’S Families' Remarkable Papal Audience, Premieres July 27, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Endovascular Management Of Free Floating Common Carotid Thrombi, Kevin Carr Md, Zachary Thwing Md, Ravishankar Shivashankar Md, Yafell Serulle Md

Radiology

• The incidence of symptomatic free-floating thrombi of the common carotid artery (CCA) is as low as 0.24-5% incidence in stroke victims. Patients are predisposed to a prothrombotic state
• Historical management options were limited to surgical and medical options both with individual attendant risk profiles
• Large thrombi can present with various degrees of clinical severity
• The endovascular approach is a viable tool to manage these patients

Roche Restarts Redesigned Phase 3 Huntington’S Disease Trial, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Are Pre-Existing Conditions Returning, And Obamacare Ending?, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Recommendations For The Design Of Therapeutic Trials For Neonatal Seizures., Janet S. Soul, Ronit Pressler, Marilee Allen, Geraldine Boylan, Heike Rabe, Ron Portman, Pollyanna Hardy, Sarah Zohar, Klaus Romero, Brian Tseng, Varsha Bhatt-Mehta, Cecil Hahn, Scott Denne, Stephane Auvin, Alexander Vinks, John Lantos, Neil Marlow, Jonathan M. Davis, International Neonatal Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy …

The Association Between Herpes Simplex Virus Type 1 Reactivation And Alzheimer’S Disease, Andrew Allee

BIO 410 Spring 2019 Research Papers

This review will focus on the interaction of herpes simplex virus type 1 (HSV-1) and its causative role in pathogenesis of Alzheimer’s disease (AD) noting specifically, the epidemiological relevance of addressing this problem, as well as the molecular pathways associated. HSV-1 reactivation tends to be one of the primary causative events that is responsible for many of the pathologies associated with AD, such as: amyloid beta (Aβ) accumulation caused by malfunctioning cleavage of amyloid precursor protein (APP) as well as tau hyperphosphorylation. HSV-1 reactivation is a primary causative event in downstream dysfunction and is also shown to be directed by …

Delirium In Long Term Care Rehabilitation Residents: A Correlational Retrospective Study, Rebecca Lerma-Kjonegaard

Dissertations

Abstract Background: Delirium is associated with devastating outcomes, cognitive loss,

decreased function and an increase risk of mortality which affects patients and places a heavy burden on family and the healthcare system. The purpose of this study was to describe the relationship between select demographics, clinical characteristics, CHART- DEL-derived delirium diagnosis and ICD-10 coded discharge delirium diagnoses among Long Term Care (LTC) rehabilitation residents.

Method: A retrospective correlational design from174 LTC rehabilitation residents age 65 years or older using EMR and hard copy charts. The setting was a Southern California community hospital-based 100-bed LTC. Abstracted data included demographic characteristics (age, …

My Huntington’S Disease Sister – And A Hero Who Strives For The Unthinkable, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Investigating Neuroinflammation And Demyelination In The Nervous System Of Twitcher Mice By The Use Of Immunohistochemistry, Irene Wilson

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Neuroinflammation and demyelination are the hallmark lesions of the Twitcher mouse—the model of Krabbe Disease. By analyzing hemibrains and sciatic nerves via immunohistochemistry, we supported the microglial hypothesis that early activation of microglial cells, macrophages, and globoid cells in the nervous system of Twitcher mice results in specific cellular polarization states that may contribute to myelin loss. The influx of activated macrophages seen in both the central and peripheral nervous systems at days 21 and 17, respectively, accounted for this polarization. Using selected M1 and M2 markers, YKL-40, and GPNMB and CD206, respectively, we proved that microglial cells and macrophages …

Assessment Of Motor Function, Motor Learning, & Olivary Climbing Fiber Distribution Within Developmental Hyperserotonemia Rat Model For Autism Spectrum Disorder, Elizabeth Diane Holland

Graduate Theses/Dissertations

While Autism Spectrum Disorder (ASD) is defined by deficits in social communication, compromised motor function and motor learning have been increasingly reported. Motor deficits could compound social impairment through delayed language acquisition, reduced opportunity for social interaction, and affected nonverbal communication. One area of interest in the investigation of motor dysfunction is the cerebellum, where altered cerebellar structure and connectivity have been reported in those diagnosed with ASD. Morphological and functional changes in cerebellar circuitry could disrupt motor skill development and may be associated with developmental alterations of the serotonergic system. Elevated blood serotonin in perinatal development, developmental hyperserotonemia (DHS), …

Vile Blood: Hereditary Degeneracy In Victorian England, Dalton Lee Brock

Theses and Dissertations from 2019

During the late 1800s, the people of England grew anxious about hereditary degeneracy. That anxiety was rooted in the medical literature of the Victorian period. Nature predetermined individuals to be either healthy or unhealthy. Unhealthy individuals were marked by degenerative mental or physical characteristics such as epilepsy. Medical professionals, including Henry Maudsley, emphasized reversion and its hereditary nature as a threat to individuals and society. All based their works and arguments on Charles Darwin’s idea of inheritance. Darwin, in turn, had adopted and modified Lamarckian inheritance to make up for the absence of an inheritance principle in his theory of …

Gigantic Stomach: A Rare Manifestation Of Duchenne Muscular Dystrophy, Amaninder Dhaliwal, Sarvani Madiraju, Banreet S. Dhindsa, Getaw W. Hassen, Fedja A. Rochling

School of Medicine Faculty Research

Duchenne muscular dystrophy (DMD) is characterized by degeneration and atrophy of skeletal, cardiac, and smooth muscles after a latent period of apparently normal development and function. The gastrointestinal manifestations start in the second decade of life and are mainly due to atrophy of smooth muscle layers. Refractory gastroparesis and chronic constipation can lead to severe gastric and small bowel dilatation, which can be life threatening. Here, we present a case of a 21-year-old male with a gigantic stomach secondary to DMD resolved with conservative management and no surgical intervention.

Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley

Senior Honors Projects, 2010-2019

Integrin subunits have been implicated in axonal and dendritic outgrowth. In particular, a strong positive association has been found between mutations in integrin beta 3 (Itgb3) and autism spectrum disorder, but little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3^-/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal …

‘Let’S Talk About Huntington’S Disease’: 2019 Hd Awareness Month Kicks Off, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Seeing Eye To Eye: A Machine Learning Approach To Automated Saccade Analysis, Maigh Attre

Honors Scholar Theses

Abnormal ocular motility is a common manifestation of many underlying pathologies particularly those that are neurological. Dynamics of saccades, when the eye rapidly changes its point of fixation, have been characterized for many neurological disorders including concussions, traumatic brain injuries (TBI), and Parkinson’s disease. However, widespread saccade analysis for diagnostic and research purposes requires the recognition of certain eye movement parameters. Key information such as velocity and duration must be determined from data based on a wide set of patients’ characteristics that may range in eye shapes and iris, hair and skin pigmentation [36]. Previous work on saccade analysis has …

An Integrative Approach To Mindfulness-Based Symptom Management For Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Lisa Barer

Mindfulness Studies Theses

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic health condition; its etiology is poorly understood, and treatment options are limited to management of symptoms. Current recommended treatment options are controversial, and evidence of effectiveness is limited. This paper proposes a novel model for symptom management of ME/CFS using mindfulness-based interventions, cognitive behavioural therapy (CBT), and relaxation techniques. A comprehensive review of available evidence is used to support this approach. The idea is that, working synergistically, these three approaches, grounded by mindfulness-based principles, can address many of the symptoms of the illness and help patients better cope and manage their day-to-day …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …