Medicine and Health Sciences Commons^™

Changes In Real-World Dispensing Of Adhd Stimulants In Youth From 2019 To 2021 In California, Anika Patel, Rishikesh Chavan, Cyril Rakovski, Richard C. Beuttler, Sun Yang

Mathematics, Physics, and Computer Science Faculty Articles and Research

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric neurobehavioral disorders in the U.S. Stimulants, classified as controlled substances, are commonly used for ADHD management. We conducted an analysis of real-world stimulants dispensing data to evaluate the pandemic’s impact on young patients (≤ 26 years) in California.

Methods: Annual prevalence of patients on stimulants per capita across various California counties from 2019 and 2021 were analyzed and further compared across different years, sexes, and age groups. New patients initiating simulants therapy were also examined. A case study was conducted to determine the impact of socioeconomic status on patient …

Dhea: A Neglected Biological Signal That May Affect Fetal And Child Development, Natasha A. Bailey, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

The stress-sensitive maternal hypothalamic–pituitary–adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Annual Research Review: The Power Of Predictability – Patterns Of Signals In Early Life Shape Neurodevelopment And Mental Health Trajectories, Elysia Poggi Davis, Laura M. Glynn

Psychology Faculty Articles and Research

The global burden of early life adversity (ELA) is profound. The World Health Organization has estimated that ELA accounts for almost 30% of all psychiatric cases. Yet, our ability to identify which individuals exposed to ELA will develop mental illness remains poor and there is a critical need to identify underlying pathways and mechanisms. This review proposes unpredictability as an understudied aspect of ELA that is tractable and presents a conceptual model that includes biologically plausible mechanistic pathways by which unpredictability impacts the developing brain. The model is supported by a synthesis of published and new data illustrating the significant …

General Cognitive Ability In High School, Attained Education, Occupational Complexity, And Dementia Risk, Jimi Huh, Thalida Em Arpawong, Tara L. Gruenewald, Gwenith G. Fisher, Carol A. Prescott, Jennifer J. Manly, Dominika Seblova, Ellen E. Walters, Margaret Gatz

Psychology Faculty Articles and Research

INTRODUCTION

We address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity.

METHODS

Using data from Project Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (N_{Cognitive Assessment} = 2477) and AD8 alone (N_{Questionnaire} = 6491) 60 years later, mediated by education and occupational complexity. Co-twin control analysis examined 82 discordant pairs for CI/AD8.

RESULTS

Education partially mediated the effect of adolescent cognition on CI in the cognitive assessment aample and …

Temporal Relation Between Pubertal Development And Peer Victimization In A Prospective Sample Of Us Adolescents, Jessica A. Marino, Elysia Poggi Davis, Laura M. Glynn, Curt A. Sandman, Jennifer Hahn-Holbrook

Psychology Faculty Articles and Research

Peer victimization typically peaks in early adolescence, leading researchers to hypothesize that pubertal timing is a meaningful predictor of peer victimization. However, previous methodological approaches have limited our ability to parse out which puberty cues are associated with peer victimization because gonadal and adrenal puberty, two independent processes, have either been conflated or adrenal puberty timing has been ignored. In addition, previous research has overlooked the possibility of reverse causality—that peer victimization might drive pubertal timing, as it has been shown to do in non-human primates. To fill these gaps, we followed 265 adolescents (47% female) prospectively across three-time points …

Correlation Enhanced Distribution Adaptation For Prediction Of Fall Risk, Ziqi Guo, Teresa Wu, Thurmon Lockhart, Rahul Soangra, Hyunsoo Yoon

Physical Therapy Faculty Articles and Research

With technological advancements in diagnostic imaging, smart sensing, and wearables, a multitude of heterogeneous sources or modalities are available to proactively monitor the health of the elderly. Due to the increasing risks of falls among older adults, an early diagnosis tool is crucial to prevent future falls. However, during the early stage of diagnosis, there is often limited or no labeled data (expert-confirmed diagnostic information) available in the target domain (new cohort) to determine the proper treatment for older adults. Instead, there are multiple related but non-identical domain data with labels from the existing cohort or different institutions. Integrating different …

Analysis Of Us Food And Drug Administration New Drug And Biologic Approvals, Regulatory Pathways, And Review Times, 1980–2022, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio, John H. Powers Iii

Pharmacy Faculty Articles and Research

U.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceutical products. We thoroughly characterized all new molecular entities, therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA) during the period 1980–2022 in the context of these laws and regulations. Throughout the study period, the FDA approved 1355 new pharmaceutical products. The median FDA review time decreased from 26.6 months prior to the Prescription Drug User Fee Act (1992), which authorized the FDA to collect fees from drug companies to 9.9 months after the Food and Drug Administration …

Running Biomechanics Differ During And After Pregnancy Compared To Females Who Have Never Been Pregnant, Jennifer J. Bagwell, Elizabeth Avila, Nicholas Reynolds, Jo Armour Smith, Kevin Valenzuela, Dimitrios Katsavelis

Physical Therapy Faculty Articles and Research

Background

Perinatal running participation has increased recently; however, pregnancy related symptoms can limit activity. Perinatal running biomechanics could inform interventions to help perinatal individuals maintain an active lifestyle.

Research question

Are perinatal running biomaechanics and muscle activation different compared to nulligravida females?

Methods

Sixteen pregnant participants completed self-selected velocity running during second trimester (2 T), third trimester (3 T), and postpartum (PP) and 16 matched controls completed these procedures once in this case control study. Kinematic, kinetic, and electromyography (EMG) data were collected using a motion capture system, force plates, and EMG electrodes. Peak trunk, pelvis, hip, knee, and ankle …

Infant Hedonic/Anhedonic Processing Index (Hapi-Infant): Assessing Infant Anhedonia And Its Prospective Association With Adolescent Depressive Symptoms, Jessica L. Irwin, Elysia Poggi Davis, Curt A. Sandman, Tallie Z. Baram, Hal S. Stern, Laura M. Glynn

Psychology Faculty Articles and Research

Background

Anhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist.

Methods

We developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Human Milk Polyunsaturated Fatty Acids Are Related To Neurodevelopmental, Anthropometric, And Allergic Outcomes In Early Life: A Systematic Review, Saori Mitguard, Olivia Doucette, John Miklavcic

Food Science Faculty Articles and Research

Polyunsaturated fatty acids are critically important for newborn nutrition and in the trajectory of growth and developmental processes throughout early life. This systematic review (PROSPERO ID: CRD42023400059) critically analyzes literature pertaining to how omega-3 and omega-6 fatty acids in human milk are related to health outcomes in early life. Literature selected for the review were published between 2005 and 2020 and included assessments in healthy term children between 0 and 5 years of age. The studies reported the relation between human milk fatty acids docosahexaenoic acid (C22:6n-3, DHA), eicosapentaenoic acid (C20:5n-3, EPA), alpha-linolenic acid (C18:3n-3, ALA), arachidonic acid (C20:4n-6, AA), …

Exploring Lgbtq+ Cultural Competency And Dei In Continuing Education: A Cross-Sectional Review Of U.S. Pharmacy Legislation, Jennifer Ko, Jeremy Carlos, Yvonne Nguyen

Pharmacy Faculty Articles and Research

Background

Lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, or other sexual orientations or gender identities (LGBTQ+) cultural competency training is offered in pharmacy curricula to variable extents. State legislation directly dictates pharmacist training through continuing pharmacy education (CPE) requirements.

Objectives

This study aimed to identify the U.S. states and the District of Columbia (D.C.) that require CPE or training on topics related to LGBTQ+ cultural competency or topics related to diversity, equity, and inclusion (DEI) in general. In addition, this study quantified and compared each state’s CPE hours required for each renewal period.

Methods

This cross-sectional study retrospectively …

Modifying Peptide/Lipid-Associated Nucleic Acids (Planas) For Crispr/Cas9 Ribonucleoprotein Delivery, Abdulelah Alhazza, Parvin Mahdipoor, Ryley Hall, Arthur Manda, Sandeep Lohan, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

With the first reports on the possibility of genome editing by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas)9 surfacing in 2005, the enthusiasm for protein silencing via nucleic acid delivery experienced a resurgence following a period of diminished enthusiasm due to challenges in delivering small interfering RNAs (siRNA), especially in vivo. However, delivering the components necessary for this approach into the nucleus is challenging, maybe even more than the cytoplasmic delivery of siRNA. We previously reported the birth of peptide/lipid-associated nucleic acids (PLANAs) for siRNA delivery. This project was designed to investigate the efficiency of …

Real-World Dispensing Of Buprenorphine In California During Prepandemic And Pandemic Periods, Yun Wang, Alexandre Chan, Richard Beuttler, Marc L. Fleming, Todd Schneberk, Michael Nichol, Haibing Lu

Pharmacy Faculty Articles and Research

Introduction: The opioid overdose crisis in the United States has become a significant national emergency. Buprenorphine, a primary medication for individuals coping with opioid use disorder (OUD), presents promising pharmacokinetic properties for use in primary care settings, and is often delivered as a take-home therapy. The COVID-19 pandemic exacerbated the scarcity of access to buprenorphine, leading to dire consequences for those with OUD. Most existing studies, primarily focused on the immediate aftermath of the COVID-19 outbreak, highlight the challenges in accessing medications for opioid use disorder (MOUDs), particularly buprenorphine. However, these studies only cover a relatively short timeframe. Methods: To …

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

Perceived Neighborhood Disorder And Type 2 Diabetes Disparities In Hispanic, Black, And White Americans, Min Ying Yu, Alfredo J. Velasquez, Belinda Campos, Jennifer W. Robinette

Psychology Faculty Articles and Research

Introduction: Approximately 32 million Americans have type 2 diabetes, and that number continues to grow. Higher prevalence rates are observed among certain subgroups, including members of marginalized racial/ethnic groups as well as residents of disordered neighborhoods (i.e., those with more trash and vandalism). Institutionalized discriminatory practices have resulted in disproportionate representation of marginalized racial/ethnic groups in disordered neighborhoods compared to non-Hispanic Whites. These neighborhood disparities may partially contribute to health disparities, given that signs of neighborhood disorder often relate to a general withdrawal from the neighborhood, minimizing opportunities for both physical and social engagement. Yet, research suggests variability across …

Describing The Evidence Linking Interprofessional Education Interventions To Improving The Delivery Of Safe And Effective Patient Care: A Scoping Review, Tamara Cadet, Joseph Cusimano, Shelley Mckearney, Julie Honaker, Cynthia O'Neal, Reza Taheri, Virginia Uhley, Yingting Zhang, Margaret Dreker, Judith S. Cohn

Pharmacy Faculty Articles and Research

Empirical evidence indicates that collaborative interprofessional practice leads to positive health outcomes. Further, there is an abundance of evidence examining student and/or faculty perceptions of learning or satisfaction about the interprofessional education (IPE) learning experience. However, there is a dearth of research linking IPE interventions to patient outcomes. The objective of this scoping review was to describe and summarize the evidence linking IPE interventions to the delivery of effective patient care. A three-step search strategy was utilized for this review with articles that met the following criteria: publications dated 2015–2020 using qualitative, quantitative or mixed methods; the inclusion of healthcare …

The Concise Guide To Pharmacology 2023/24: Enzymes, Stephen P. H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, James A. Davies, Stephanie Annett, Detlan Boison, Kathryn Elisa Burns, Carmen Dessauer, Jürg Gertsch, Nuala Ann Helsby, Angela A. Izzo, Rennolds Ostrom, Andreas Papapetropoulos, Nigel J. Pyne, Susan Pyne, Tracy Robson, Roland Seifert, Johannes-Peter Stasch, Csaba Szabo, Mario Van Der Stelt, Albert Van Der Vliet, Val Watts, Szu Shen Wong

Pharmacy Faculty Articles and Research

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Postgraduate Medical Trainees At A Ugandan University Perceive Their Clinical Learning Environment Positively But Differentially Despite Challenging Circumstances: A Cross-Sectional Study, Paul E. Alele, Joshua Kiptoo, Kathleen Hill-Besinque

Pharmacy Faculty Articles and Research

Purpose

The clinical learning environment is an essential component in health professions’ education. Data are scant on how postgraduate trainees in sub-Saharan Africa perceive their medical school learning environments, and how those perceptions contribute to their engagement during training, their emotional wellbeing, and career aspirations. This study examined perceptions of postgraduate medical trainees (residents) in a resource-limited setting, regarding their learning environment and explored perceptual contributions to their career engagement during training. The data reported contribute to understanding how clinical learning environments can be improved in low-resource settings in Uganda and elsewhere.

Methods

This study was done at the Faculty …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Structural Analysis And Activity Correlation Of Amphiphilic Cyclic Antimicrobial Peptides Derived From The [W4R4] Scaffold, Shaima Ahmed El-Mowafi, Anastasia G. Konshina, Eman H. M. Mohammed, Nikolay A. Krylov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W₄R₄], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W₄R₄] scaffold, …

South Los Angeles Park Observation Research, Valeria N. Delgado, Melissa R. Ramos

Student Scholar Symposium Abstracts and Posters

The health impact of elevated gang activity on the residents of South Los Angeles has been a pressing concern with limited research. Thus, this study aimed to understand the potential health repercussions within this context, specifically by examining how different patrolling systems influence community members' physical activity in public parks. To increase security, the city of Los Angeles implemented police patrol programs in multiple high-risk parks. Concurrently, the Advocates for Urban Peace & Unity (APUU), a local community organization, introduced a novel approach of community-led park patrolling. Essentially, respected community members volunteer to patrol and maintain safety and order in …

Identifying The Effects Of Function-Based Exercise On Postural Stability And Gait In Patients With Parkinson’S Disease, Kasey Markell, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

This project seeks to identify a correlation between consistent, functional exercise and posture, balance, stability and gait in patients with Parkinson’s Disease (PD). PD is a neurodegenerative disease that decreases levels of dopamine in the Basal Ganglia of the brain, resulting in symptoms such as excessive freezing or erratic, involuntary movements, ultimately affecting a person’s ability to ambulate safely and independently. This study consisted of three main approaches to build a firm base of knowledge for this field of research. The first component was to test the limits of stability in healthy individuals for a baseline comparison to people with …

Efficacy And Safety Of Ciltacabtagene Autoleucel And Idecabtagene Vicleucel In Multiple Myeloma Patients, Buthainah Ghanem, Marc L. Fleming, Lawrence M. Brown, Rosa Rodriguez-Monguio, Enrique Seoane-Vazquez

Student Scholar Symposium Abstracts and Posters

Background: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are chimeric antigen receptor (CAR) T-cell therapies used to treat adult patients with relapsed or refractory multiple myeloma (rrMM) after at least four lines of therapy. However, no head-to-head clinical trials to compare them have been conducted.

Objective: To compare between CARTITUDE-1 and KarMMa clinical trials in terms of efficacy, safety, and patient characteristics.

Method: Overall response rate (ORR) and safety signals were compared using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at p < 0.05. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan–Meier method with a log-rank test. Patient characteristics were compared using the chi-square test. Statistical analyses were conducted using Microsoft Excel and R version 4.0.5.

Results: Statistically significant differences were observed between cilta-cel and ide-cel in terms of ORR, complete response …

Multi-Site Identification And Generalization Of Clusters Of Walking Behaviors In Individuals With Chronic Stroke And Neurotypical Controls, Natalia Sanchez, Nicolas Schweighofer, Sara J. Mulroy, Ryan T. Roemmich, Tricia M. Kesar, Gelsy Torres-Oviedo, Beth E. Fisher, James M. Finley, Carolee J. Winstein

Physical Therapy Faculty Articles and Research

Background

Objectives

Methods

Multi-Site Identification And Generalization Of Clusters Of Walking Behaviors In Individuals With Chronic Stroke And Neurotypical Controls, Natalia Sánchez, Nicolas Schweighofer, Sara J. Mulroy, Ryan T. Roemmich, Trisha M. Keshar, Gelsy Torres-Oviedo, Beth E. Fisher, James M. Finley, Carolee J. Winstein

Physical Therapy Faculty Articles and Research

Background

Objectives

Methods

Erythrocyte–Brain Endothelial Interactions Induce Microglial Responses And Cerebral Microhemorrhages In Vivo, Hai Zhang, Rachita K. Sumbria, Rudy Chang, Jiahong Sun, David H. Cribbs, Todd C. Holmes, Mark J. Fisher, Xiangmin Xu

Pharmacy Faculty Articles and Research

Background

Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC–brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.

Methods

RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC–brain endothelial interactions associated with …