Medical Sciences Commons^™

Translational Initiative To Minimize Childhood Hemiparesis After Asymmetrical Perinatal Brain Injury, Susan V. Duff, Emily Garavatti, Terrie Inder

Physical Therapy Faculty Articles and Research

The purpose of this perspective paper is to present a translational approach aimed at identifying the critical periods in brain development during which to provide neuroprotective and neurorestorative strategies, followed by prehensile training, to minimize hemiparesis and foster skill acquisition after asymmetrical perinatal brain injury (APBI). We contend that hemiparesis could be minimized after APBI through a multimodal sequential approach based on timely implementation of evidence-based intervention strategies. If APBI is identified early, neuroprotective techniques can be used in the first 10 days of life to minimize cell death. This can be followed in the next 3 months by the …

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

Online Decoding Of Rat Self-Paced Locomotion Speed From Eeg Using Recurrent Neural Networks, Alejandro De Miguel, Nelson Totah, Uri Maoz

Psychology Faculty Articles and Research

Objective. Accurate and reliable neural decoding of locomotion holds promise for advancing clinical applications such as rehabilitation and prosthetic control, as well as for understanding neural correlates of action. Recent studies have demonstrated successful decoding of locomotion kinematics across species in motorized treadmill settings. However, efforts to decode locomotion speed directly and continuously in more natural contexts—where pace is self-selected rather than externally imposed—are scarce, and those that exist generally achieve only modest accuracy and require intracranial implants. Here, we aim to decode self-paced locomotion speed non-invasively and continuously using cortex-wide electroencephalography (EEG) recordings from rats. Approach. We introduce an …

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

A Caveat Regarding The Unfolding Argument: Implications Of Plasticity, Viknas N. O'Reilly-Shah, Alessandro Maria Selvitella, Aaron Schurger

Psychology Faculty Articles and Research

The unfolding argument in the neuroscience of consciousness posits that causal structure cannot account for consciousness because any recurrent neural network (RNN) can be “unfolded” into a functionally equivalent feedforward neural network (FNN) with identical input–output behavior. Subsequent debate has focused on dynamical properties and philosophy of science critiques. We examine a boundary condition on the unfolding argument for RNN systems with rapid plasticity in their connection weights. We demonstrate through rigorous mathematical proofs that rapid plasticity negates the functional equivalence between the RNN and the FNN. Our proofs address history-dependent plasticity, dynamical systems analysis, information-theoretic considerations, perturbational stability, complexity …

Increased Neural Activity In The Bed Nucleus Of The Stria Terminalis Of Uninfected Canaries After Observation Of Infected Conspecifics, Madeleine Chang, Sophia Santangelo, Devon Comito, Bennett Hardy, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Recent evidence suggests that the immune system may be upregulated in anticipation of pathogen exposure, yet the neural mechanisms that respond to and signal impending infection risk remain poorly understood. We investigated neural responses to infection risk in uninfected hosts observing infected conspecifics, using the canary (Serinus canaria domestica)—Mycoplasma gallisepticum host–parasite system. We focused on five brain regions of interest, comprising three nodes of the social decision-making network—preoptic area, bed nucleus of the stria terminalis (BNST) and hippocampus—a stress modulatory region (paraventricular nucleus) and a visual processing region (nucleus rotundus). After 1 h of observing infected canaries, …

Protocol For Spatial Profiling Of Immune Cells In The Mouse Cornea And Conjunctiva Using Nanostring Geomx Dsp And Ncounterpro Platforms, Lois Kim, Karthikeyan Ramasamy, Ajay Sharma

Pharmacy Faculty Articles and Research

Quantification of immune cells and their activation status in a spatially specific manner in a healthy or diseased tissue is a valuable tool in immunology. Here, we present a protocol for the spatial profiling of immune cells in the mouse cornea and conjunctiva. We describe steps for immunostaining with photocleavable oligonucleotide-conjugated antibodies, selecting regions of interest (ROIs), and collecting UV-cleaved oligonucleotides using GeoMx DSP. We then detail procedures for hybridizing collected oligonucleotides, cartridge blotting using nCounter Pro Prep, data acquisition, and data analysis.

Accelerated Molecular Aging In Neighborhood Poverty: A Racial/Ethnic Comparison, Jennifer Robinette, Jennifer Smith

Psychology Faculty Articles and Research

In the US, racial/ethnic health disparities are undeniable and partially stem from residing in low SES neighborhoods. Associations between neighborhood SES and health may have some underlying molecular mechanisms reflected in the epigenome. Yet, neighborhood characteristics are not always experienced the same way for all residents, and questions remain regarding whether those most exposed to low SES neighborhoods build greater resilience to, or embody greater harmful and cumulative outcomes from, such neighborhoods. The present study tested the hypothesis that greater neighborhood poverty would relate to accelerated epigenetic aging on the Horvath, Hannum, PhenoAge, and GrimAge clocks, and that these associations …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Abnormalities In Sensorimotor Brain Function Are Related To Chronicity Of Low Back Pain, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Jesse V. Jacobs, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Maladaptive plasticity in the brain may contribute to chronic low back pain (LBP) and underlie the altered postural control of the lumbopelvic musculature that is evident in some individuals with LBP. We recently described an MRI-compatible leg-raise paradigm to measure brain activity associated with lumbopelvic postural control. The objective of this study was to compare brain function in young adults with and without a history of LBP and to determine relationships between brain function, pain, and postural control characteristics. We recruited 55 participants with a history of LBP, who were asymptomatic when studied, and 30 healthy controls. Postural control during …

Twenty Minutes Of Corsi Block Tapping Task Training Does Not Improve Mental Rotation In Adults With Stroke, Sarah A. Kettlety, Giuliet L. Kibler, Andrew Hooyman, Christina K. Holl, Sydney Y. Schaefer, Kristan A. Leech

Physical Therapy Faculty Articles and Research

Background: Visuospatial function is commonly impaired post-stroke and is associated with motor learning and recovery. A single, twenty-minute Corsi Block Tapping Task (CBTT) training session improved visuospatial function in young neurotypical adults; however, it is unclear whether this training would improve visuospatial function in adults with stroke.

Objective: To understand if a single, twenty-minute CBTT training session improved visuospatial function in adults with stroke compared to a no-training control group of adults with stroke.

Methods: Participants post-stroke were assigned to one of two groups. The training group completed twenty minutes of computerized CBTT training. The control group completed a survey …

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …

Neonatal Striatal Volume Is Associated With Infant Anhedonia, Melissa Nevarez-Brewster, Catherine H. Demers, Jessica L. Irwin, Laura M. Glynn, Martin A. Styner, Mercedes Hoeflich Haase, M. Camille Hoffman, Diego A. Pizzagalli, Benjamin L. Hankin, Elysia Poggi Davis

Psychology Faculty Articles and Research

Anhedonia is increasingly recognized as a transdiagnostic risk factor for psychopathology. New evidence demonstrates that anhedonia is present in infancy and early childhood. Structural variability in striatal regions involved in reward processing and pleasure seeking is concurrently linked to anhedonia, yet few studies have examined whether striatal differences presage anhedonia, and none have examined prospective associations before middle childhood. The present study examined whether neuroanatomical markers that confer risk for anhedonia can be detected as early as the neonatal period. Specifically, we tested whether the volume of striatal regions in neonates predicted the emergence of infant anhedonic behaviors at six …

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …

A Multi-Measurement Study Of The Relation Between Deliberation And Volition, Guillaume P. Pech, Emilie A. Caspar, Elisabeth Pacherie, Axel Cleeremans, Uri Maoz

Psychology Faculty Articles and Research

Historically, voluntary action and volition more generally have been investigated through the lens of meaningless decisions. Importantly, these findings have been used in the debate about key notions like free will and moral responsibility. However, more recent claims have challenged the possibility of generalizing findings from a meaningless context to a more meaningful one. The current study investigates the markers of volition, specifically comparing meaningful and meaningless decisions. In an effort to maximize their monetary gain, 50 participants repeatedly deliberated between two options, making either rewarded choices—hard-deliberation decisions (where the options differed along two dimensions) or easy-deliberation decisions (where the …

Sex-Specific Effects Of Early-Life Unpredictability On Hippocampal And Amygdala Responses To Novelty In Adolescents, Elysia Poggi Davis, Bianca T. Leonard, Robert J. Jirsaraie, David B. Keator, Steven L. Small, Curt A. Sandman, Victoria B. Risbrough, Hal S. Stern, Laura M. Glynn, Michael A. Yassa, Tallie Z. Baram, Jerod M. Rasmussen

Psychology Faculty Articles and Research

Background

Unpredictable childhood experiences are an understudied form of early-life adversity that impact neurodevelopment. The neurobiological processes by which exposure to early-life unpredictability impact development and vulnerability to psychopathology remain poorly understood. In the current study, we investigated the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala.

Methods

Participants included 150 youths (54% female). Early-life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC). Participants engaged in 1 or more task–functional magnetic resonance imaging scans between the ages of 8 and 17 (223 total observations) measuring blood oxygen level–dependent (BOLD) …

Neural Associations Between Fingerspelling, Print, And Signs: An Erp Priming Study With Deaf Readers, Brittany Lee, Sofia E. Ortega, Priscilla M. Martinez, Katherine J. Midgley, Phillip J. Holcomb, Karen Emmorey

Communication Sciences and Disorders Faculty Articles and Research

Fingerspelling is a leading predictor of reading ability for deaf people who use a signed language, but few neuroimaging studies have examined how it supports reading. We used event-related potentials to investigate how fingerspelled words prime printed words. Twenty-four skilled deaf adult readers completed a Go/No-Go task while viewing printed English word targets following related and unrelated primes in one of three conditions: printed English words, American Sign Language (ASL) signs, and fingerspelled words. N400 priming effects were strong across all three conditions. Early N400 effects were similar for printed word primes and fingerspelled word primes, suggesting shared orthographic representations. …

Utilizing Pharmacogenomics To Improve Students' Self-Perception On The Interprofessional Competencies Of Roles And Responsibilities, And Teams And Teamwork, Amanda Brown, Moom R. Roosan, Robert Goldsteen, Scott D. Ochs, Reza Taheri

Pharmacy Faculty Articles and Research

Introduction

Pharmacogenomics (PGx) is an emerging discipline with the potential to revolutionize personalized medicine, but its successful implementation requires interprofessional collaboration. To address this need, a virtual interprofessional education (IPE) session was designed for student pharmacists and medical students to engage in a case-based learning experience.

Objective

The primary objective was to develop and implement an IPE activity focused on a patient case requiring PGx-guided dual antiplatelet therapy and to assess students' perceptions of two Interprofessional Education Collaborative (IPEC) Version 3 Core Competencies. A secondary objective was to identify key lessons from the session.

Methods

Pharmacist and physician faculty collaboratively …

Partial Least Squares Multimodal Analysis Of Brain Network Correlates Of Language Deficits In Aphasia, Sigfus Kristinsson, Dirk B. Den Ouden, Chris Rorden, Roger Newman-Norlund, Lisa Johnson, Janina Wilmskoetter, Ezequiel Gleichgerrcht, Argye E. Hillis, Gregory Hickok, Julius Fridriksson, Leonardo Bonilha

Communication Sciences and Disorders Faculty Articles and Research

Lesion-symptom mapping techniques are essential to determine brain regions critical for language functions. However, high collinearity in neuroimaging and behavioural data remains a challenge for distinguishing neural substrates supporting multiple language domains (shared variance) and those subserving specific language functions (unique variance). Here, we employed a novel approach to multimodal lesion-symptom mapping using multivariate partial least squares regression to delineate the latent structure of lesion-behavioural mapping in aphasia and decompose the shared and unique neural determinants of language impairments. A total of 86 participants with chronic (>12-month post-stroke) aphasia after left hemisphere strokes were examined. Language impairment was assessed …

Benchmarking Machine Learning Models In Lesion-Symptom Mapping For Predicting Language Outcomes In Stroke Survivors, Deepa Tilwani, Christian O'Reilly, Nicholas Riccardi, Valerie L. Shalin, Dirk B. Den Ouden, Julius Fridriksson, Svetlana V. Shinkareva, Amit P. Sheth, Rutvik H. Desai

Communication Sciences and Disorders Faculty Articles and Research

Several decades of research have investigated the neural connections between stroke-induced brain damage and language difficulties. Typically, lesion-symptom mapping (LSM) studies that address this connection have relied on mass univariate statistics, which do not account for multidimensional relationships between variables. Machine learning (ML) techniques, which can capture these intricate connections, offer a promising complement to LSM methods. To test this promise, we benchmarked ML models on structural and functional MRI to predict aphasia severity (N = 238) and naming impairment (N = 191) for a cohort of chronic-stage stroke survivors. We used nested cross-validation to examine performance along …

Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang

Pharmacy Faculty Articles and Research

Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …

Cost-Effective Solutions For High-Throughput Enzymatic Dna Methylation Sequencing, Amy Longtin, Marina M. Watowich, Baptiste Sadoughi, Rachel M. Petersen, Sarah F. Brosnan, Kenneth Buetow, Qiuyin Cai, Cayo Biobank Research Unit, Vanderbilt University, Michael D. Gurven, James P. Higham, Heather M. Highland, Yi-Ting Huang, Hillard Kaplan, Thomas S. Kraft, Yvonne A. L. Lim, Jirong Long, Amanda D. Melin, Michael J. Montagne, Jamie Roberson, Kee Seong Ng, Michael L. Platt, India A. Schneider-Crease, Jonathan Stieglitz, Benjamin C. Trumble, Vivek Venkataraman, Ian J. Wallace, Jie Wu, Noah Snyder-Mackler, Angela Jones, Alexander G. Bick, Amanda J. Lea

ESI Publications

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, development, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target a subset of the genome). Most common whole genome and reduced representation techniques rely on bisulfite conversion, which can damage DNA resulting in DNA loss and sequencing biases. Enzymatic methyl sequencing (EM-seq) was recently proposed to overcome these issues, but thorough benchmarking of EM-seq combined with …

Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in …

Variance In Heart Rate Variability Between Healthy And Concussed Individuals, Sebastian Herrera Vargas, Joonsuk Choi

Student Scholar Symposium Abstracts and Posters

Heart-Rate Variability (HRV) is the interval between each individual heartbeat, from p-wave to p-wave on an electrocardiogram (ECG). In general, a high HRV indicates that a person has a healthy heart with effective stress management skills. This value means that one branch of the nervous system is not overpowering the other, sympathetic vs parasympathetic–for example. Generally, HRV is related to vagal tone, the ability for your body to activate the parasympathetic system and relax when imminent danger is not present. However, when someone is concussed, the entirety of their autonomic regulation can be affected such that their HRV is altered. …

The Legacy Of William M. Pardridge (1947–2024) On The Science And Fields Concerned With The Physiology Of The Blood-Brain Barrier And The Transport Of Drugs To The Brain, Ruben J. Boado, Ulrich Bickel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

This article highlights the scientific achievements and professional career of William M. Pardridge, who passed away on 18th of June 2024. He was born in 1947 in Bethesda, Maryland, USA. William, known affectionately as Bill, was one of the most influential researchers in the blood-brain barrier (BBB) field. Bill’s research contributions to the field spun over 6 decades at the University of California, Los Angeles, and it was focused on the molecular physiology of the BBB, including the carrier-mediated transport of nutrients and small molecule drugs, the receptor-mediated transport of peptides and molecular Trojan horses, gene therapy of the brain …

Cracking The Code Of Hbv Persistence: Cutting-Edge Approaches To Targeting Cccdna In Chronic Hepatitis B With Or Without Pyogenic Liver Abscesses, Umar Saeed, Zahra Zahid Piracha, Mahmood Khan, Muhammad Nouman Tariq, Syed Shahan Gilani, Muhammad Raza, Rakshana Munuswamy, Naveen Bose, Dilber Uzun Ozsahin, Ilker Özşahin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, …

Probing For Intentions: The Early Readiness Potential Does Not Reflect Awareness Of Motor Preparation, Jake Gavenas, Aaron Schurger, Uri Maoz

Psychology Faculty Articles and Research

Voluntary actions are typically preceded by the readiness potential (RP), a negative midfrontal electroencephalography (EEG) deflection that begins ~2 s before movement. What cognitive and neural process the RP reflects and how it relates to conscious intention remain unclear due to conflicting findings. We investigated the neural basis and cognitive significance of the RP in a novel probe-based paradigm. Contrary to prior reports, we found that pre-probe RP buildups were not related to reported awareness of motor preparation. Computational modeling suggested that the best explanation for these results is via metacognitive access to stochastic accumulation. Reported preparation was also related …

The Quic-Sp: A Spanish Language Tool Assessing Unpredictability In Early Life Is Linked To Physical And Mental Health, Sabrina R. Liu, Natasha A. Bailey, Sara Romero-González, Amy Moors, Belinda Campos, Elysia P. Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Accumulating evidence indicates that unpredictable signals in early life represent a unique form of adverse childhood experiences (ACEs) associated with disrupted neurodevelopmental trajectories in children and adolescents. The Questionnaire of Unpredictability in Childhood (QUIC) was developed to assess early life unpredictability, encompassing social, emotional, and physical unpredictability in a child’s environment, and has been validated in three independent cohorts. However, the importance of identifying ACEs in diverse populations, including non-English speaking groups, necessitates translation of the QUIC. The current study aims to translate and validate a Spanish language version of the QUIC (QUIC-SP) and assess its associations with mental and …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

Chronic Heavy Alcohol Intake And Liver-Specific Lrp-1 Reduction Increase Amyloidosis In Alzheimer’S Disease Mice, Devaraj V. Chandrashekar, G. Chuli Roules, Ross A. Steinberg, Urvashi R. Panchal, Nataraj Jagadeesan, Adenike Oyegbesan, Trinh Roselyn, Joshua Yang, Sharda R. Bhagwat, Hiya Rakholia, Rutvi D. Mevawala, Moom Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Chronic heavy alcohol drinking may be a modifiable risk factor for Alzheimer’s disease (AD), but studies in rodent AD models more closely mimic chronic moderate alcohol drinking in humans and largely focus on the brain. The role of the liver, which is significantly impacted by chronic heavy alcohol intake, in driving brain changes in alcohol-dependent AD remains unexplored. Our study using intragastric-ethanol feeding, which mimics chronic heavy alcohol intake in humans, in C57BL/6J mice showed significant AD-relevant changes in the brain and liver. Therefore, we aimed to investigate how hepatic changes using this model of chronic heavy drinking drive …