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Articles 211 - 240 of 486
Full-Text Articles in Neurology
Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth
Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth
Faculty, Staff and Student Publications
Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …
International Prevalence And Mechanisms Of Sars-Cov-2 In Childhood Arterial Ischemic Stroke During The Covid-19 Pandemic, Lauren A Beslow, Shannon C Agner, Jonathan D Santoro, Dipak Ram, Jenny L Wilson, Dana Harrar, Brian Appavu, Stuart M Fraser, Thomas Rossor, Marcela D Torres, Manoëlle Kossorotoff, Yenny C Zuñiga Zambrano, Marta Hernández-Chávez, Sahar M A Hassanein, Dimitrios Zafeiriou, Michael M Dowling, Ilona Kopyta, Nicholas V Stence, Timothy J Bernard, Nomazulu Dlamini
International Prevalence And Mechanisms Of Sars-Cov-2 In Childhood Arterial Ischemic Stroke During The Covid-19 Pandemic, Lauren A Beslow, Shannon C Agner, Jonathan D Santoro, Dipak Ram, Jenny L Wilson, Dana Harrar, Brian Appavu, Stuart M Fraser, Thomas Rossor, Marcela D Torres, Manoëlle Kossorotoff, Yenny C Zuñiga Zambrano, Marta Hernández-Chávez, Sahar M A Hassanein, Dimitrios Zafeiriou, Michael M Dowling, Ilona Kopyta, Nicholas V Stence, Timothy J Bernard, Nomazulu Dlamini
Faculty, Staff and Student Publications
BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2.
METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 >years, numbers of incident AIS cases among children (29 days to <18 >years), frequency …18>18>
Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity In Human Sensory Neuron Somata Parallel Alterations Described In Spontaneously Active Rodent Nociceptors, Robert Y North, Max A Odem, Yan Li, Claudio Esteves Tatsui, Ryan M Cassidy, Patrick M Dougherty, Edgar T Walters
Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity In Human Sensory Neuron Somata Parallel Alterations Described In Spontaneously Active Rodent Nociceptors, Robert Y North, Max A Odem, Yan Li, Claudio Esteves Tatsui, Ryan M Cassidy, Patrick M Dougherty, Edgar T Walters
Faculty, Staff and Student Publications
Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to …
The Effects Of Supplemental Dietary Chitosan On Broiler Performance And Myopathic Features Of White Striping, Mary F Love, Andrea Nicole Brooks, Sonya D Cox, Munachi Okpala, Gail Cooksey, Audrey Sarah Cohen, Anjail Z Sharrief
The Effects Of Supplemental Dietary Chitosan On Broiler Performance And Myopathic Features Of White Striping, Mary F Love, Andrea Nicole Brooks, Sonya D Cox, Munachi Okpala, Gail Cooksey, Audrey Sarah Cohen, Anjail Z Sharrief
Faculty, Staff and Student Publications
Introduction
Stroke, a life-threatening stressor, often negatively impacts stroke-survivor (SS) quality of life (QoL). Annual age-adjusted incidence and death rates for stroke are significantly higher among Black Americans than among White Americans. Racism, a significant stressor, occurs at structural, cultural, and interpersonal levels and contributes to health disparities for Black SS. Resilience, a dynamic process of positive adaptation to significant stress, is impacted by factors or resources both internal and external to the individual. This study aims to examine the effects of experiences of racism and resilience on Black SS QoL during early stroke recovery. This article presents the study …
Emergency Department Communication In Persons Living With Dementia And Care Partners: A Scoping Review, Christopher R Carpenter, Jesseca Leggett, Fernanda Bellolio, Marian Betz, Ryan M Carnahan, David Carr, Michelle Doering, Jennie Chin Hansen, Eric D Isaacs, Deborah Jobe, Kathleen Kelly, Nancy Morrow-Howell, Beth Prusaczyk, Bob Savage, Joe Suyama, Allan S Vann, Kristin L Rising, Ula Hwang, Manish N Shah
Emergency Department Communication In Persons Living With Dementia And Care Partners: A Scoping Review, Christopher R Carpenter, Jesseca Leggett, Fernanda Bellolio, Marian Betz, Ryan M Carnahan, David Carr, Michelle Doering, Jennie Chin Hansen, Eric D Isaacs, Deborah Jobe, Kathleen Kelly, Nancy Morrow-Howell, Beth Prusaczyk, Bob Savage, Joe Suyama, Allan S Vann, Kristin L Rising, Ula Hwang, Manish N Shah
Faculty, Staff and Student Publications
OBJECTIVES: To synthesize published research exploring emergency department (ED) communication strategies and decision-making with persons living with dementia (PLWD) and their care partners as the basis for a multistakeholder consensus conference to prioritize future research.
DESIGN: Systematic scoping review.
SETTINGS AND PARTICIPANTS: PLWD and their care partners in the ED setting.
METHODS: Informed by 2 Patient-Intervention-Comparison-Outcome (PICO) questions, we conducted systematic electronic searches of medical research databases for relevant publications following standardized methodological guidelines. The results were presented to interdisciplinary stakeholders, including dementia researchers, clinicians, PLWD, care partners, and advocacy organizations. The PICO questions included: How does communication differ for …
Predictors Of Disease Activity And Worsening In Relapsing-Remitting Multiple Sclerosis, Yinan Zhang, Stacey Cofield, Gary Cutter, Stephen Krieger, Jerry S Wolinsky, Fred Lublin
Predictors Of Disease Activity And Worsening In Relapsing-Remitting Multiple Sclerosis, Yinan Zhang, Stacey Cofield, Gary Cutter, Stephen Krieger, Jerry S Wolinsky, Fred Lublin
Faculty, Staff and Student Publications
Background and objectives: Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening.
Methods: The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of …
Detecting Cognitive Impairment And Dementia In The Emergency Department: A Scoping Review, Armin Nowroozpoor, Jeff Dussetschleger, William Perry, Mary Sano, Amy Aloysi, Michael Belleville, Alexandria Brackett, Jon Mark Hirshon, William Hung, Joan Michelle Moccia, Ugochi Ohuabunwa, Manish N Shah, Ula Hwang
Detecting Cognitive Impairment And Dementia In The Emergency Department: A Scoping Review, Armin Nowroozpoor, Jeff Dussetschleger, William Perry, Mary Sano, Amy Aloysi, Michael Belleville, Alexandria Brackett, Jon Mark Hirshon, William Hung, Joan Michelle Moccia, Ugochi Ohuabunwa, Manish N Shah, Ula Hwang
Faculty, Staff and Student Publications
OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).
DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.
SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients.
METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and …
Patient Preference For Virtual Versus In-Person Visits In Neuromuscular Clinical Practice, Komal Hafeez, Hani Kushlaf, Husam Al-Sultani, Anny-Claude Joseph, Zoya Zaeem, Zaeem Siddiqi, Shannon Laboy, Michael Pulley, Ali A Habib, Nathaniel M Robbins, Sean Zadeh, Muhammad Ubaid Hafeez, Yessar Hussain, Alexandria Melendez-Zaidi, Charles Kassardjian, Kristin Johnson, Holly Leonhard, Suur Biliciler, Jorge E Patino Murillas, Aziz I Shaibani
Patient Preference For Virtual Versus In-Person Visits In Neuromuscular Clinical Practice, Komal Hafeez, Hani Kushlaf, Husam Al-Sultani, Anny-Claude Joseph, Zoya Zaeem, Zaeem Siddiqi, Shannon Laboy, Michael Pulley, Ali A Habib, Nathaniel M Robbins, Sean Zadeh, Muhammad Ubaid Hafeez, Yessar Hussain, Alexandria Melendez-Zaidi, Charles Kassardjian, Kristin Johnson, Holly Leonhard, Suur Biliciler, Jorge E Patino Murillas, Aziz I Shaibani
Faculty, Staff and Student Publications
INTRODUCTION/AIMS: It is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences.
METHODS: Telephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed.
RESULTS: Five hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% …
Ankle2-Related Microcephaly: A Variable Microcephaly Syndrome Resembling Zika Infection, Ajay X Thomas, Nichole Link, Laurie A Robak, Gail Demmler-Harrison, Emily C Pao, Audrey E Squire, Savannah Michels, Julie S Cohen, Anne Comi, Paolo Prontera, Alberto Verrotti Di Pianella, Giuseppe Di Cara, Livia Garavelli, Stefano Giuseppe Caraffi, Carlo Fusco, Roberta Zuntini, Kendall C Parks, Elliott H Sherr, Mais O Hashem, Sateesh Maddirevula, Fowzan S Alkuraya, Isphana A F Contractar, Jennifer E Neil, Christopher A Walsh, Hugo J Bellen, Hsiao-Tuan Chao, Robin D Clark, Ghayda M Mirzaa
Ankle2-Related Microcephaly: A Variable Microcephaly Syndrome Resembling Zika Infection, Ajay X Thomas, Nichole Link, Laurie A Robak, Gail Demmler-Harrison, Emily C Pao, Audrey E Squire, Savannah Michels, Julie S Cohen, Anne Comi, Paolo Prontera, Alberto Verrotti Di Pianella, Giuseppe Di Cara, Livia Garavelli, Stefano Giuseppe Caraffi, Carlo Fusco, Roberta Zuntini, Kendall C Parks, Elliott H Sherr, Mais O Hashem, Sateesh Maddirevula, Fowzan S Alkuraya, Isphana A F Contractar, Jennifer E Neil, Christopher A Walsh, Hugo J Bellen, Hsiao-Tuan Chao, Robin D Clark, Ghayda M Mirzaa
Duncan NRI Faculty and Staff Publications
Objective: This study delineates the clinical and molecular spectrum of ANKLE2-related microcephaly (MIC), as well as highlights shared pathological mechanisms between ANKLE2 and the Zika virus.
Methods: We identified 12 individuals with MIC and variants in ANKLE2 with a broad range of features. Probands underwent thorough phenotypic evaluations, developmental assessments, and anthropometric measurements. Brain imaging studies were systematically reviewed for developmental abnormalities. We functionally interrogated a subset of identified ANKLE2 variants in Drosophila melanogaster.
Results: All individuals had MIC (z-score ≤ -3), including nine with congenital MIC. We identified a broad range of brain abnormalities including simplified cortical gyral pattern, …
Genome Sequencing In The Parkinson Disease Clinic, Emily J Hill, Laurie A Robak, Rami Al-Ouran, Jennifer Deger, Jamie C Fong, Paul Jerrod Vandeventer, Emily Schulman, Sindhu Rao, Hiba Saade, Joseph M Savitt, Rainer Von Coelln, Neeja Desai, Harshavardhan Doddapaneni, Sejal Salvi, Shannon Dugan-Perez, Donna M Muzny, Amy L Mcguire, Zhandong Liu, Richard A Gibbs, Chad Shaw, Joseph Jankovic, Lisa M Shulman, Joshua M Shulman
Genome Sequencing In The Parkinson Disease Clinic, Emily J Hill, Laurie A Robak, Rami Al-Ouran, Jennifer Deger, Jamie C Fong, Paul Jerrod Vandeventer, Emily Schulman, Sindhu Rao, Hiba Saade, Joseph M Savitt, Rainer Von Coelln, Neeja Desai, Harshavardhan Doddapaneni, Sejal Salvi, Shannon Dugan-Perez, Donna M Muzny, Amy L Mcguire, Zhandong Liu, Richard A Gibbs, Chad Shaw, Joseph Jankovic, Lisa M Shulman, Joshua M Shulman
Duncan NRI Faculty and Staff Publications
Background and objectives: Genetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics.
Methods: In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well …
Plasma Amyloid-Β Dynamics In Late-Life Major Depression: A Longitudinal Study, Nunzio Pomara, Davide Bruno, Chelsea Reichert Plaska, Jaime Ramos-Cejudo, Ricardo S Osorio, Anilkumar Pillai, Bruno P Imbimbo, Henrik Zetterberg, Kaj Blennow
Plasma Amyloid-Β Dynamics In Late-Life Major Depression: A Longitudinal Study, Nunzio Pomara, Davide Bruno, Chelsea Reichert Plaska, Jaime Ramos-Cejudo, Ricardo S Osorio, Anilkumar Pillai, Bruno P Imbimbo, Henrik Zetterberg, Kaj Blennow
Faculty, Staff and Student Publications
Depressed individuals are twice as likely to develop Alzheimer’s disease (AD) as compared to controls. Brain amyloid-β (Aβ) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aβ dynamics and depression. The aim of this study was to test if plasma Aβ levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-β1-40 (Aβ40) and amyloid-β1-42 (Aβ42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the Aβ42/Aβ40 plasma ratio was significantly …
Parenteral Nsaids For Acute Treatment Of Migraine: Adherence To The Ihs Guidelines For Controlled Trials, John G. Curran, John Waters, Hsiangkuo Yuan
Parenteral Nsaids For Acute Treatment Of Migraine: Adherence To The Ihs Guidelines For Controlled Trials, John G. Curran, John Waters, Hsiangkuo Yuan
Department of Neurology Faculty Papers
Background: Parenteral non-steroidal anti-inflammatory drugs (NSAIDs) are important alternatives to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. With increasing research on using parenteral NSAIDs for acute migraine, it is critical to examine the quality of these studies. Our goal was to assess the adherence of these trials to the International Headache Society (IHS) controlled trial guidelines for acute treatment of migraine. Methods: We queried PubMed for clinical trials investigating parenteral NSAIDs for acute treatment of migraine in adult patients. We developed a 14-point scoring system based on the essential components of the IHS guidelines. …
Sox9 Directs Divergent Epigenomic States In Brain Tumor Subtypes, Debosmita Sardar, Hsiao-Chi Chen, Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali, Ganesh Rao, Stephen C Mack, Benjamin Deneen
Sox9 Directs Divergent Epigenomic States In Brain Tumor Subtypes, Debosmita Sardar, Hsiao-Chi Chen, Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali, Ganesh Rao, Stephen C Mack, Benjamin Deneen
Duncan NRI Faculty and Staff Publications
Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZR
Cardiovascular Adverse Events In Oncology Trials: Understanding And Appreciating The Differences Between Clinical Trial Data And Real-World Reports, Michael S Ewer, Jay Herson
Cardiovascular Adverse Events In Oncology Trials: Understanding And Appreciating The Differences Between Clinical Trial Data And Real-World Reports, Michael S Ewer, Jay Herson
Duncan NRI Faculty and Staff Publications
Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These differences may lead to confusion, as different levels of risks abound in the literature, and the true cardiac risk of using some agents is uncertain. Additionally, such discrepancies may lead to the creation of over-cautious surveillance algorithms. Reasons for these reported differences are complex and often reflect subtleties in the criteria for individual patient evaluation. Both clinical trial data and real-world data have potential flaws that make reconciliation problematic. Importantly, however, both provide crucial information regarding the …
Can Variables From The Electronic Health Record Identify Delirium At Bedside?, Ariba Khan, Kayla Heslin, Michelle Simpson, Michael L. Malone
Can Variables From The Electronic Health Record Identify Delirium At Bedside?, Ariba Khan, Kayla Heslin, Michelle Simpson, Michael L. Malone
Journal of Patient-Centered Research and Reviews
Delirium, a common and serious disorder in older hospitalized patients, remains underrecognized. While several delirium predictive models have been developed, only a handful have focused on electronic health record (EHR) data. This prospective cohort study of older inpatients (≥ 65 years old) aimed to determine if variables within our health system’s EHR could be used to identify delirium among hospitalized patients at the bedside. Trained researchers screened daily for delirium using the 3-minute diagnostic Confusion Assessment Method (3D-CAM). Patient demographic and clinical variables were extracted from the EHR. Among 408 participants, mean age was 75 years, 60.8% were female, and …
Serum And Plasma Levels Of Brain-Derived Neurotrophic Factor In Individuals With Eating Disorders (Eds): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Sara Bagherieh, Parsa Mirzayi, Amirali Kalantari, Omid Mirmosayyeb, Antônio L Teixeira, Nima Rezaei
Serum And Plasma Levels Of Brain-Derived Neurotrophic Factor In Individuals With Eating Disorders (Eds): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Sara Bagherieh, Parsa Mirzayi, Amirali Kalantari, Omid Mirmosayyeb, Antônio L Teixeira, Nima Rezaei
Faculty, Staff and Student Publications
Background: Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, development, and plasticity. Evidence suggests that fluctuations in peripheral levels (i.e., plasma or serum) of BDNF are associated with eating behaviors. Nevertheless, the findings are inconsistent. The purpose of this study is to determine if serum or plasma levels of BDNF are altered in individuals with eating disorders (EDs) compared to controls.
Methods: We conducted a systematic search of the core electronic medical databases from inception to March 2022 and identified observational studies that compared individuals with EDs to controls without EDs on serum or plasma levels of BDNF. …
Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee
Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee
Engineering Science Faculty Publications
Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …
Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan
Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan
Faculty, Staff and Student Publications
Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed based on expression levels of transcription factors (e.g. T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11bhigh subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11bhigh …
Neuronal Activity Induces Glucosylceramide That Is Secreted Via Exosomes For Lysosomal Degradation In Glia, Liping Wang, Guang Lin, Zhongyuan Zuo, Yarong Li, Seul Kee Byeon, Akhilesh Pandey, Hugo J Bellen
Neuronal Activity Induces Glucosylceramide That Is Secreted Via Exosomes For Lysosomal Degradation In Glia, Liping Wang, Guang Lin, Zhongyuan Zuo, Yarong Li, Seul Kee Byeon, Akhilesh Pandey, Hugo J Bellen
Duncan NRI Faculty and Staff Publications
Recessive variants in GBA1 cause Gaucher disease, a prevalent form of lysosome storage disease. GBA1 encodes a lysosomal enzyme that hydrolyzes glucosylceramide (GlcCer) into glucose and ceramide. Its loss causes lysosomal dysfunction and increased levels of GlcCer. We generated a null allele of the Drosophila ortholog Gba1b by inserting the Gal4 using CRISPR-Cas9. Here, we show that Gba1b is expressed in glia but not in neurons. Glial-specific knockdown recapitulates the defects found in Gba1b mutants, and these can be rescued by glial expression of human GBA1. We show that GlcCer is synthesized upon neuronal activity, and it is transported …
Renin-Angiotensin System In Huntington's Disease: Evidence From Animal Models And Human Patients, Lucas M Kangussu, Natalia P Rocha, Priscila A C Valadão, Thatiane C G Machado, Kívia B Soares, Julliane V Joviano-Santos, Leigh B Latham, Gabriela D Colpo, Ana Flávia Almeida-Santos, Erin Furr Stimming, Ana Cristina Simões E Silva, Antônio L Teixeira, Aline Silva Miranda, Cristina Guatimosim
Renin-Angiotensin System In Huntington's Disease: Evidence From Animal Models And Human Patients, Lucas M Kangussu, Natalia P Rocha, Priscila A C Valadão, Thatiane C G Machado, Kívia B Soares, Julliane V Joviano-Santos, Leigh B Latham, Gabriela D Colpo, Ana Flávia Almeida-Santos, Erin Furr Stimming, Ana Cristina Simões E Silva, Antônio L Teixeira, Aline Silva Miranda, Cristina Guatimosim
Faculty, Staff and Student Publications
The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington's disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside …
Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Michael A Lopez, Ying Si, Xianzhen Hu, Valentyna Williams, Fuad Qushair, Jackson Carlyle, Lyndsy Alesce, Michael Conklin, Shawn Gilbert, Marcas M Bamman, Matthew S Alexander, Peter H King
Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Michael A Lopez, Ying Si, Xianzhen Hu, Valentyna Williams, Fuad Qushair, Jackson Carlyle, Lyndsy Alesce, Michael Conklin, Shawn Gilbert, Marcas M Bamman, Matthew S Alexander, Peter H King
Faculty, Staff and Student Publications
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor β (TGFβ) signaling. In this report, we investigated the major transducers of TGFβ signaling, i.e., receptor Smads (R-Smads), in DMD patient skeletal muscle and observed a 48-fold increase in Smad8 mRNA. Smad1, Smad2, Smad3, and Smad5 mRNA were only minimally increased. A similar pattern was observed in the muscle from the mdx5cv mouse. Western blot analysis showed upregulation of phosphorylated Smad1, Smad5, and Smad8 …
Evaluation Of A Process Change Using An Updated Sedation Protocol, Rachel Allen
Evaluation Of A Process Change Using An Updated Sedation Protocol, Rachel Allen
Dissertations
Problem: Pediatric delirium is continuing to increase intensive care environments and for patients who require mechanical ventilation and continuous sedative medications. Delirium is harmful to the patient creating lasting neurologic and mental health issues along with prolonged hospitalization and increased healthcare cost
Method: For this quality improvement (QI) project, a descriptive observational study was used to evaluate the implementation of a sedation protocol for patients who are mechanically ventilated and on continuous sedative medications. This was completed with the use of retrospective chart reviews three months prior to implementation and three months after the new protocol was implemented. Nurses were …
Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Alexis Bavencoffe, Emily A Spence, Michael Y Zhu, Anibal Garza-Carbajal, Kerry E Chu, Ona E Bloom, Carmen W Dessauer, Edgar T Walters
Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Alexis Bavencoffe, Emily A Spence, Michael Y Zhu, Anibal Garza-Carbajal, Kerry E Chu, Ona E Bloom, Carmen W Dessauer, Edgar T Walters
Faculty, Staff and Student Publications
Neuropathic pain is a major, inadequately treated challenge for people with spinal cord injury (SCI). While SCI pain mechanisms are often assumed to be in the CNS, rodent studies have revealed mechanistic contributions from primary nociceptors. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain. A major question is whether extrinsic chemical signals help to drive ongoing electrical activity after SCI. People living with SCI exhibit acute and chronic elevation of circulating levels of macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models. Probable nociceptors isolated from male rats and exposed …
Gene-Based Therapeutics For Rare Genetic Neurodevelopmental Psychiatric Disorders, Beverly L Davidson, Guangping Gao, Elizabeth Berry-Kravis, Allison M Bradbury, Carsten Bönnemann, Joseph D Buxbaum, Gavin R Corcoran, Steven J Gray, Heather Gray-Edwards, Robin J Kleiman, Adam J Shaywitz, Dan Wang, Huda Y Zoghbi, Terence R Flotte, Sitra Tauscher-Wisniewski, Cynthia J Tifft, Mustafa Sahin
Gene-Based Therapeutics For Rare Genetic Neurodevelopmental Psychiatric Disorders, Beverly L Davidson, Guangping Gao, Elizabeth Berry-Kravis, Allison M Bradbury, Carsten Bönnemann, Joseph D Buxbaum, Gavin R Corcoran, Steven J Gray, Heather Gray-Edwards, Robin J Kleiman, Adam J Shaywitz, Dan Wang, Huda Y Zoghbi, Terence R Flotte, Sitra Tauscher-Wisniewski, Cynthia J Tifft, Mustafa Sahin
Duncan NRI Faculty and Staff Publications
We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies.
Pilot Study For Correlation Of Heart Rate Variability And Dopamine Transporter Brain Imaging In Patients With Parkinsonian Syndrome, Devdutta S Warhadpande, Jiayan Huo, William A Libling, Carol Stuehm, Bijan Najafi, Scott Sherman, Hong Lei, Janet Meiling Roveda, Phillip H Kuo
Pilot Study For Correlation Of Heart Rate Variability And Dopamine Transporter Brain Imaging In Patients With Parkinsonian Syndrome, Devdutta S Warhadpande, Jiayan Huo, William A Libling, Carol Stuehm, Bijan Najafi, Scott Sherman, Hong Lei, Janet Meiling Roveda, Phillip H Kuo
Center on Aging Staff Publications
Background: Parkinsonian syndrome (PS) is a broad category of neurodegenerative movement disorders that includes Parkinson disease, multiple system atrophy (MSA), progressive supranuclear palsy, and corticobasal degeneration. Parkinson disease (PD) is the second most common neurodegenerative disorder with loss of dopaminergic neurons of the substantia nigra and, thus, dysfunction of the nigrostriatal pathway. In addition to the motor symptoms of bradykinesia, rigidity, tremors, and postural instability, nonmotor symptoms such as autonomic dysregulation (AutD) can also occur. Heart rate variability (HRV) has been used as a measure of AutD and has shown to be prognostic in diseases such as diabetes mellitus and …
Transcription Factor Runx3 Mediates Plasticity Of Thgm Cells Toward Th1 Phenotype, Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
Transcription Factor Runx3 Mediates Plasticity Of Thgm Cells Toward Th1 Phenotype, Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
Department of Neurology Faculty Papers
GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that …
Stroke Care: Achieving Recommended Door To Computed Tomography Times In Ambulatory Patients Presenting To The Emergency Department Of A Rural Hospital Through The Application Of American Stroke Association Guidelines, Ricardo Paitz
Doctor of Nursing Practice Projects
Background: Time matters in stroke care, and every second counts because the extent of irreversible neuronal damage increases over time (Saver, 2006). Therefore, the American Stroke Association (ASA) recommends a door to computed tomography time of 20 minutes or less for patients presenting with signs of acute ischemic stroke. This time metric in stroke care is often not met, resulting in the delay of care of patients which translates to poorer outcomes, including death and a decreased quality of life in patients who have suffered an acute ischemic stroke (Kamal, Sheng, et al., 2017).
Purpose: The purpose of this DNP …
Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Ganne Chaitanya, Johnson P Hampson, Emilia Toth, Norma J Hupp, Jaison S Hampson, John C Mosher, Sandipan Pati, Samden D Lhatoo, Nuria Lacuey
Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Ganne Chaitanya, Johnson P Hampson, Emilia Toth, Norma J Hupp, Jaison S Hampson, John C Mosher, Sandipan Pati, Samden D Lhatoo, Nuria Lacuey
Faculty, Staff and Student Publications
Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.
Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out …
A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Pasquale Striano, Stéphane Auvin, Abigail Collins, Rita Horvath, Ingrid E Scheffer, Michal Tzadok, Ian Miller, Mary Kay Koenig, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo
A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Pasquale Striano, Stéphane Auvin, Abigail Collins, Rita Horvath, Ingrid E Scheffer, Michal Tzadok, Ian Miller, Mary Kay Koenig, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo
Faculty, Staff and Student Publications
Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).
Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52.
Results: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure …
Contributions Of Semantic And Phonological Working Memory To Narrative Language Independent Of Single Word Production: Evidence From Acute Stroke, Rachel Zahn, Tatiana T Schnur, Randi C Martin
Contributions Of Semantic And Phonological Working Memory To Narrative Language Independent Of Single Word Production: Evidence From Acute Stroke, Rachel Zahn, Tatiana T Schnur, Randi C Martin
Faculty, Staff and Student Publications
Neuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. …