Medical Specialties Commons^™

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …

Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

The Grenada Learning And Memory Scale: Psychometric Features And Normative Data In Caribbean Preschool Children, Karen Blackmon, Roberta Evans, Lauren Mohammed, Kemi Burgen, Erin Ingraham, Bianca Punch, Rashida Isaac, Toni Murray, Jesma Noel, Cora Belmar-Roberts

Brain and Mind Institute

Objective: Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially pertinent in low- and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. The Grenada Learning and Memory Scale (GLAMS) was created for use in limited resource settings and includes a shopping list and face-name association test. Here, we present psychometric and normative data for the GLAMS in a Grenadian preschool sample.

Methods: Typically developing children between 36 and 72 months of age, primarily English speaking, were recruited from public preschools in …

Improving Adherence Amongst Post-Stroke Patients In The Outpatient Setting, Olivea Adetu

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This quality improvement (QI) project aimed to enhance medication adherence and follow-up rates through structured, personalized phone calls to recently discharged post-stroke patients. The project was implemented at an outpatient neuroscience clinic in Greater Houston.

BACKGROUND

Low medication adherence and poor attendance at the first neurology follow-up appointment among post-stroke patients contribute to increased morbidity and higher risk of recurrent stroke. Despite receiving discharge instructions, many patients do not consistently take their prescribed medications or attend their initial neurology visit.

METHODOLOGY

Guided by the Plan-Do-Study-Act (PDSA) cycle, this project engaged a medical assistant to call recently discharged stroke patients …

Considerations For Widespread Implementation Of Blood-Based Biomarkers Of Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali

Brain and Mind Institute

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges …

Recommendations For Clinical Implementation Of Blood-Based Biomarkers For Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali, Chinedu Momoh

Brain and Mind Institute

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational …

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

Clinical Outcome-Guided Deep Temporal Clustering For Disease Progression Subtyping, Dulin Wang, Xiaotian Ma, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Objective: Complex diseases exhibit heterogeneous progression patterns, necessitating effective capture and clustering of longitudinal changes to identify disease subtypes for personalized treatments. However, existing studies often fail to design clustering-specific representations or neglect clinical outcomes, thereby limiting the interpretability and clinical utility.

Method: We design a unified framework for subtyping longitudinal progressive diseases. We focus on effectively integrating all data from disease progressions and improving patient representation for downstream clustering. Specifically, we propose a clinical Outcome-Guided Deep Temporal Clustering (OG-DTC) that generates representations informed by clustering and clinical outcomes. A GRU-based seq2seq architecture captures the temporal dynamics, and the model …

Cerebrovascular Disease Is Associated With Alzheimer's Plasma Biomarker Concentrations In Adults With Down Syndrome, Andreas Engvig, Karl Trygve Kalleberg, Lars T. Westlye, Esten Høyland Leonardsen, Alzheimer’S Disease Neuroimaging Initiative Consortium

Neurology Faculty Publications

DNA methylation age (MA), brain age (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship and combined potential for prediction of cognitive impairment and future dementia risk using the ADNI database. Of several MA algorithms, DunedinPACE and GrimAge2, associated with memory, were combined in a composite MA alongside BA and a data-driven FI in predictive analyses. Pairwise correlations between age- and sex-adjusted measures for MA (aMA), aBA, and aFI were low. FI outperformed BA and MA in all diagnostic tasks. A model including age, sex, and aFI achieved an area under the …

Long-Term Efficacy And Safety Of Cannabidiol In Patients With Tuberous Sclerosis Complex: 3-Year Results From The Cannabidiol Expanded Access Program, Arie Weinstock, E Martina Bebin, Daniel Checketts, Gary D Clark, Jerzy P Szaflarski, Laurie E Seltzer, Elizabeth A Thiele, Farhad Sahebkar

Faculty, Staff and Students Publications

OBJECTIVE: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.

METHODS: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. …

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery …

Author Correction: Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

No abstract provided.

Does Delaying Levodopa Prevent Motor Complications In Parkinson's Disease? A Meta-Analysis, Luis Guilherme Ramanzini, Julia M Frare, Luís F M Camargo, Juliana O F Silveira, Joseph Jankovic

Faculty, Staff and Students Publications

Background: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD).

Objectives: We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD.

Methods: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias.

Results: Seven studies with a total …

On The Power Of Constructive Criticism, Anna Devor, Androu Abdalmalak, Taner Akkin, Yeka Aponte, George J. Augustine, Sabrina Brigadoi, Erin M. Buckley, Robert E. Campbell, Stefan A. Carp, Jean-Yves Chatton, Jerry L. Chen, Ji-Xin Cheng, Tomáš Cižmár, Robert J. Cooper, Ippeita Dan, Patrick J. Drew, Turgut Durduran, Valentina Emiliani, Tommaso Fellin, Amanda J. Foust, Ling Fu, Amir Gandjbakhche, Judit Gervain, Ariel Gilad, Edgar Guevara Codina, Xue Han, Elizabeth M. Hillman, Ute Hochgeschwender, Song Hu, Na Ji, Prakash Kara, Beop-Min Kim, Tiffany S. Ko, Duygu Kuzum, Jérôme Lecoq, Rickson C. Mesquita, Timothy H. Murphy, U. Valentin Nägerl, Nozomi Nishimura, Yumie Ono, Nisan Ozana, Francesco S. Pavone, Darcy S. Peterka, Ferruccio Pisanello, Anna Wang Roe, Andy Y. Shih, Shy Shoham, François St-Pierre, Sungho Tak, Lin Tian, Kai Wang, Martin Wolf, Ji Yi, Ofer Yizhar, Meryem A. Yucel

Faculty, Staff and Students Publications

The editorial discusses the practice of peer review for SPIE Neurophotonics.

Feature Extraction For Generative Medical Imaging Evaluation: New Evidence Against An Evolving Trend, Mckell Woodland, Austin Castelo, Mais Al Taie, Jessica Albuquerque Marques Silva, Mohamed Eltaher, Frank Mohn, Alexander Shieh, Suprateek Kundu, Joshua P Yung, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

Fréchet Inception Distance (FID) is a widely used metric for assessing synthetic image quality. It relies on an ImageNet-based feature extractor, making its applicability to medical imaging unclear. A recent trend is to adapt FID to medical imaging through feature extractors trained on medical images. Our study challenges this practice by demonstrating that ImageNet-based extractors are more consistent and aligned with human judgment than their RadImageNet counterparts. We evaluated sixteen StyleGAN2 networks across four medical imaging modalities and four data augmentation techniques with Fréchet distances (FDs) computed using eleven ImageNet or RadImageNet-trained feature extractors. Comparison with human judgment via visual …

Simultaneous Ipsilateral Hip And Knee Dislocation: Management And Outcome – A Case Report, Christian G Falgons, Stephen J Warner

Faculty, Staff and Student Publications

Case: This clinical case report presents a 40-year-old male who sustained an ipsilateral hip and knee dislocation with ipsilateral femoral head fracture and incomplete femoral neck fracture following a motorcycle collision.

Conclusion: This report describes acute and later definitive orthopedic care and management, with focus on urgent interventions and timing of immediate treatments. Given the presented patient's favorable clinical outcomes, return to baseline activities, and absence of significant sequelae following injury, the considerations from the acute management and surgical planning of this patient's injuries can be used as a reference for treating the rare injury of ipsilateral knee and hip …

Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, …

Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high …

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …

Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators

Faculty, Staff and Student Publications

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …

Effectiveness Of Electronic Learning Courses On Neurologist Knowledge Of Epilepsy Classification: A Study Based On The Kirkpatrick Model, Zohrehsadat Mirmoghtadaie, Mahmoud Mohammadi, Ali Reza Tavasoli, Reza Shervin Badv, Mahmoud Reza Ashrafi, Gholam Reza Zamani, Sareh Hosseinpour, Abdolmajid Omrani

Jefferson Institute of Molecular Medicine Papers and Presentations

Background: Nowadays, it is generally accepted that focusing on in-service training can lead to organizational progress and improvements in the training process. Objectives: Considering the high prevalence of epilepsy in children and the use of new technologies in education, the purpose of this study was to conduct an electronic educational course on epilepsy classification guidelines based on the guidelines of pediatric neurologists and to evaluate the effectiveness of the course using the Kirkpatrick model. Methods: This study was conducted in 2020. The study population comprised pediatric neurologists from universities of medical sciences throughout the country. Inclusion criteria included participation in …

Strategic Stabilization Of Arousal Boosts Sustained Attention, Jan Willem De Gee, Zakir Mridha, Marisa Hudson, Yanchen Shi, Hannah Ramsaywak, Spencer Smith, Nishad Karediya, Matthew Thompson, Kit Jaspe, Hong Jiang, Wenhao Zhang, Matthew J Mcginley

Duncan NRI Faculty and Staff Publications

Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal detection theoretic, hazard function …

Thrombectomy For Stroke With Large Infarct On Noncontrast Ct: The Tesla Randomized Clinical Trial, Writing Committee For The Tesla Investigators, Albert J Yoo, Osama O Zaidat, Sunil A Sheth, Ansaar T Rai, Santiago Ortega-Gutierrez, Curtis A Given, Syed F Zaidi, Ramesh Grandhi, Hugo Cuellar, Maxim Mokin, Jeffrey M Katz, Amer Alshekhlee, Muhammad A Taqi, Sameer A Ansari, Adnan H Siddiqui, Nobl Barazangi, Joey D English, Alberto Maud, Jawad Kirmani, Rishi Gupta, Dileep R Yavagal, Jason Tarpley, Dhruvil J Pandya, Marshall C Cress, Sushrut Dharmadhikari, Kaiz S Asif, Tareq Kass-Hout, Ajit S Puri, Nazli Janjua, Aniel Q Majjhoo, Aamir Badruddin, Randall C Edgell, Rakesh Khatri, Larry Morgan, Anmar Razak, Alicia Zha, Priyank Khandelwal, Nils Mueller-Kronast, Dennis J Rivet, Thomas Wolfe, Brian Snelling, Ali Sultan-Qurraie, Shao-Pow Lin, Rajkamal Khangura, Alejandro M Spiotta, Parita Bhuva, Sergio Salazar-Marioni, Eugene Lin, Abdul R Tarabishy, Edgar A Samaniego, Murali K Kolikonda, Mouhammad A Jumaa, Vivek K Reddy, Pankaj Sharma, Olvert A Berkhemer, Pieter-Jan Van Doormaal, Adriaan C G M Van Es, Wim H Van Zwam, Bart J Emmer, Ludo F Beenen, Charles B L M Majoie, Nancy Buderer, Michelle A Detry, Anna Bosse, Todd L Graves, Christina Saunders, Lucas Elijovich, Ashutosh Jadhav, Mary Patterson, Hannah Slight, Kristine Below, Sami Al Kasab, Tesla Investigators

Faculty, Staff and Student Publications

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at …

Protocol For The Derivation Of Primary Cancer Stem Cell Lines From Human Ependymal Tumors, Cory M Richman, Peter B Dirks, Michael D Taylor, Kulandaimanuvel Antony Michealraj

Faculty, Staff and Students Publications

Cancer stem cells (CSCs) established from surgical biopsies closely mimic the human context and can be used to investigate disease mechanisms, genetic fitness, and therapeutic evaluation. Here, we present a protocol for the derivation of primary patient-derived CSC lines from ependymal tumors. We describe the necessary steps, from surgical intervention and biopsy to the dissociation of ependymomas to derive cultures. We then detail procedures for cell line propagation and define the characteristics of these primary cancer cell lines. For complete details on the use and execution of this protocol, please refer to Michealraj et al.

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

Predictive Value Of Follow-Up Infarct Volume On Functional Outcomes In Middle Cerebral Artery M2 Segment Vessel Occlusion Stroke Treated With Mechanical Thrombectomy, Vivek Yedavalli, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT.

Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute …