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Full-Text Articles in Medicine and Health Sciences

Anterior Circulation Location-Specific Results For Stent- Assisted Coiling – Carotid Versus Distal Aneurysms: 1- Year Outcomes From The Neuroform Atlas Stent Pivotal Trial, Ricardo A. Hanel, Gustavo M. Cortez, Brian T. Jankowitz, Eric Sauvageau, Amin Aghaebrahim, Eugene Lin, Ashutosh P. Jadhav, Bradley Gross, Ahmad Khaldi, Rishi Gupta, Donald Frei, David Loy, Lori Lyn Price, Steven W. Hetts, Osama O. Zaidat, Atlas Investigators Jan 2024

Anterior Circulation Location-Specific Results For Stent- Assisted Coiling – Carotid Versus Distal Aneurysms: 1- Year Outcomes From The Neuroform Atlas Stent Pivotal Trial, Ricardo A. Hanel, Gustavo M. Cortez, Brian T. Jankowitz, Eric Sauvageau, Amin Aghaebrahim, Eugene Lin, Ashutosh P. Jadhav, Bradley Gross, Ahmad Khaldi, Rishi Gupta, Donald Frei, David Loy, Lori Lyn Price, Steven W. Hetts, Osama O. Zaidat, Atlas Investigators

Neurology Faculty Publications

Background The Neuroform Atlas Stent System is an established treatment modality for unruptured anterior and posterior circulation intracranial aneurysms. Location-specific results are needed to guide treatment decision- making. However, it is unclear whether there are differences in safety and efficacy outcomes between carotid and more distal anterior circulation aneurysms. Methods The ATLAS IDE trial was a prospective, multicenter, single- arm, open-label interventional study that evaluated the safety and efficacy of the Neuroform Atlas Stent System. We compared differences in efficacy and safety outcomes of proximal internal carotid artery (ICA) versus distal and bifurcation anterior circulation aneurysms.

Results Of 182 cases, …


Estrogen’S Sex-Specific Effects On Ischemic Cell Death And Estrogen Receptor Mrna Expression In Rat Cortical Organotypic Explants, Amanda L. Trout, Christopher J. Mclouth, Jenna Westberry, Tomoko Sengoku, Melinda E. Wilson Jan 2024

Estrogen’S Sex-Specific Effects On Ischemic Cell Death And Estrogen Receptor Mrna Expression In Rat Cortical Organotypic Explants, Amanda L. Trout, Christopher J. Mclouth, Jenna Westberry, Tomoko Sengoku, Melinda E. Wilson

Neurology Faculty Publications

Estrogens, such as the biologically active 17-β estradiol (E2), regulate not only reproductive behaviors in adults, but also influence neurodevelopment and neuroprotection in both females and males. E2, contingent upon the timing and concentration of the therapy, is neuroprotective in female and male rodent models of stroke. In Vivo studies suggest that E2 may partially mediate this neuroprotection, particularly in the cortex, via ERα. In Vitro studies, utilizing a chemically induced ischemic injury in cortical explants from both sexes, suggest that ERα or ERβ signaling is needed to mediate the E2 protection. Since we know that the timing and concentration …


Adverse Outcomes Of Co-Occurring Methamphetamine And Opioid Use Among Pregnant And Postpartum Women, Hope Tevis Jan 2024

Adverse Outcomes Of Co-Occurring Methamphetamine And Opioid Use Among Pregnant And Postpartum Women, Hope Tevis

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background

Overdose mortality rates increased significantly between 2018 and 2021 in the United States (NIH, 2023). Moreover, pregnant and postpartum women (PPW), who were aged 35 to 44 were observed to have the highest overdose mortality rates (NIH, 2023). Although there is existing research that examines the increase of co-occurring opioid and methamphetamine use, it still remains understudied when specifically focusing on PPW. This analysis intends to explore this gap in research by 1) exploring the history of co-occurring methamphetamine and opioid use among PPW who were seeking residential treatment, 2) highlighting the adverse health outcomes that follow co-use among …


Evaluating A High School Mrsa Prevention Program: A Case Study, Jamie Henning Jan 2024

Evaluating A High School Mrsa Prevention Program: A Case Study, Jamie Henning

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

MRSA poses a significant health risk to athletes nationwide. This case study examines the application of an online training module to address knowledge gaps regarding Methicillin-resistant Staphylococcus aureus (MRSA) among key decision-makers for high school athletes. It reviews the development and initial evaluation of a web-based training program designed to empower decision-makers with the knowledge to prevent MRSA infection and respond to suspected cases. Program evaluation recommended expanding the training module to wrestling staff with improved evaluation methods while continuing implementation and effectiveness assessment for the football staff. Despite initial data quality limitations, the online training module evaluation offered valuable …


A Case Study In Program Evaluation: Evaluation Of A Mrsa Education Program, Kangai Miriti Jan 2024

A Case Study In Program Evaluation: Evaluation Of A Mrsa Education Program, Kangai Miriti

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Program evaluations provide a deeper understanding of program components to promote effective program implementation. This evaluation follows the CDC’s 6-step Framework for Program Evaluation in Public Health to evaluate a MRSA education program. This evaluation has been prepared to be presented to the Lexington- Fayette County Health Department.


A Case Study In Evaluation, Laura Nagle Jan 2024

A Case Study In Evaluation, Laura Nagle

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The Lexington – Fayette County Health Department is proposing a comprehensive evaluation of programming focused on preventing MRSA infections among high school athletes within Fayette County Public Schools. This document describes the recommended evaluation process.


A Case Study In Program Evaluation, Kayla Shepherd Jan 2024

A Case Study In Program Evaluation, Kayla Shepherd

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

A program evaluation of a case study presented by the College of Public Health. This case study included a fictitious MRSA outbreak at a Kentucky high school football camp and the response of the Fayette County Public School System (FCPS) and the Lexington-Fayette County Health Department (LFCHD). Using the Centers for Disease Control and Prevention's Framework for Program Evaluation, I evaluated the Educational Infectious Disease Program designed by the FCPS and LFCHD. I provided recommendations to help improve the success of the program.


Team Up Against Overdose Deaths, Mary Elizabeth Pendergrass Jan 2024

Team Up Against Overdose Deaths, Mary Elizabeth Pendergrass

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This grant proposal describes a community collaboration strategy for reducing overdose deaths. Utilizing a Community Advisory Board, the goal of the project is to increase awareness, knowledge, and usage of the Good Samaritan Law to obtain emergency medical care.


A Case Study In Program Evaluation, Sydney Wilcoxson Jan 2024

A Case Study In Program Evaluation, Sydney Wilcoxson

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Evaluation is a critical component of a successful evidence-based health promotion program or intervention. In public health, evaluations ensure that interventions are achieving their intended objectives, provide feedback on program strengths and weaknesses, and serve as a mechanism of accountability and transparency to stakeholders so that they know their invested resources are being utilized in the most efficient manner. Without evaluation, it would be much more difficult to understand how well the intervention is working, and communication between stakeholders would be significantly affected.

A recently confirmed Methicillin-resistant staphylococcus aureus (MRSA) outbreak on a Fayette County Public Schools (FCPS) high school …


The Relationship Between Self-Reported Depressive Symptoms At 3 Timepoints And Infant Sleep Practices At 6-Month Follow-Up In A Population Of Mothers In Santo Domingo, Ecuador, Kassidy Lane Jan 2024

The Relationship Between Self-Reported Depressive Symptoms At 3 Timepoints And Infant Sleep Practices At 6-Month Follow-Up In A Population Of Mothers In Santo Domingo, Ecuador, Kassidy Lane

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Background

Previous studies have linked maternal depression with poor infant sleep (e.g., waking up at night and infants having trouble settling to sleep). This study examined the relationship between maternal depressive symptoms at three time points and safe infant sleep at 6-month follow-up.

Methods

Data was collected from a randomized clinical trial including 100 women recruited from a health center in Santo Domingo, Ecuador during their third trimester of pregnancy. Log-binomial regression was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of safe infant sleeping at 6 months among mothers who reported depressive symptoms at 3 …


Interprofessional Collaboration In A Lung Cancer Screening Learning Collaborative, Angela Fu Jan 2024

Interprofessional Collaboration In A Lung Cancer Screening Learning Collaborative, Angela Fu

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The primary purpose of this paper is to identify partners and levels of engagement through investigating participants of the Kentucky Lung Cancer Screening Learning Collaborative: Achieving Equity, which was led by the Kentucky Lung Cancer Education Awareness Detection Survivorship (KY LEADSTM) Prevention and Early Detection team now known as the Quality Implementation of Lung Cancer Screening (QUILSTM) group in collaboration with the Healthy Kentucky Initiative supported by UK HealthCare. A secondary objective was to identify and categorize organizational and system policies related to lung cancer and screenings. The six-session series focused on equity in lung cancer …


The Relationship Between Social Vulnerability And Cardiovascular Disease Outcomes In Kentucky, Karcyn Brummett Jan 2024

The Relationship Between Social Vulnerability And Cardiovascular Disease Outcomes In Kentucky, Karcyn Brummett

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Cardiovascular disease (CVD) is a leading cause of death in the United States, and some regions, such as the Appalachian region, have relatively higher burdens of CVD deaths. CVD has been shown to be influenced by various social factors, with some leading to an increased risk of disease.

Objective: The objectives of this study were to determine the potential correlation between social vulnerability and cardiovascular disease outcomes in Kentucky and how this varies in the Appalachian versus non-Appalachian regions of the state.

Methods: Heart disease death rates and county social vulnerability index (SVI) values in Kentucky were evaluated to …


Adolescent Vaccination Rates And Pharmacists' Ability To Prescribe And Administer, Paul Jake Faulkner Jan 2024

Adolescent Vaccination Rates And Pharmacists' Ability To Prescribe And Administer, Paul Jake Faulkner

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Vaccines are arguably the most significant advancement in healthcare in the prevention of diseases. The CDC has created a series of recommendations to help guide providers and patients toward a healthier future with vaccines. These recommendations were adopted by the Health People Goals 2020 and 2030 to increase each state's rates of completing specific vaccination series by defined age thresholds. This capstone aims to assess if there is a correlation between vaccination rates and pharmacists; specifically to see if states that give less restrictions about vaccinating would have higher rates. It is also important to see if states with more …


Cardiovascular Disease Among Commercially Insured Adults With Type 1 Diabetes In The Us , 2016-2019, Orighomisan F. Agboghoroma Jan 2024

Cardiovascular Disease Among Commercially Insured Adults With Type 1 Diabetes In The Us , 2016-2019, Orighomisan F. Agboghoroma

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objectives: The objective of this study is to examine the overall as well as age- and sex-specific burden of cardiovascular disease (CVD) among adults with type 1 diabetes (T1D) in the US using nationwide commercial claims data from 2016-2019.

Research Design and Methods We used nationwide commercial claims data (1/1/2016-12/31/2019) from Merative™MarketScan to identify adults ≥20 years with T1D (ascertained using ICD-10 codes). CVD was ascertained using ICD-10 diagnostic codes for myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, peripheral arterial disease, and stroke. The annual prevalence and age-specific prevalence of CVD were calculated. Age-adjusted prevalence of CVD …


Changes In Primary Care Availability In Appalachia, Whitney Beckett Jan 2024

Changes In Primary Care Availability In Appalachia, Whitney Beckett

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The Affordable Care Act (ACA) was a groundbreaking moment in the United States healthcare system. It affected many different aspects of the system, including access to primary care professionals. Primary care professionals provide a key role in American’s health, especially when it comes to preventative care. With one-third of Americans experiencing barriers to such access, a solution is desperately needed to increase said access. These barriers are especially profound in low-income, underserved areas such as the Appalachian regions of Georgia, Kentucky, Tennessee, and West Virginia. The ACA attempted to increase access via Medicaid expansion; however, not all States expanded their …


Empirical Insights Into Survivorship Care: A Cross-Sectional Study Of Coc Accredited Hospitals In Kentucky, Amanda M. Beckett Jan 2024

Empirical Insights Into Survivorship Care: A Cross-Sectional Study Of Coc Accredited Hospitals In Kentucky, Amanda M. Beckett

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

ABSTRACT

Background:

Cancer survivorship care programs play a vital role in supporting cancer survivors and improving their quality of life. Understanding the landscape of survivorship and the potential barriers is key to optimizing care delivery.

Methods:

The primary purpose of this cross-sectional study was to explore existing cancer survivorship care programs offered by Commission on Cancer (CoC) accredited hospitals in Kentucky. Data from the Markey Cancer Affiliate Network (MCCAN) from 2022 through 2023 was analyzed. Variables included hospital characteristics such as rural code, types of survivorship services offered, and reported barriers to these services.

Results:

Analysis of n=19 CoC facilities …


Novel Cannabinoid Use Among Young Adults In Lexington, Kentucky, Victoria A. Hamilton Jan 2024

Novel Cannabinoid Use Among Young Adults In Lexington, Kentucky, Victoria A. Hamilton

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Purpose: The purpose of this study was to implement a survey to estimate the prevalence of novel cannabinoid use among young adults in Lexington, Kentucky, and to examine modes of use and motivations for novel cannabinoid use. The primary hypothesis of this study was that many respondents would indicate medical reasons for using novel cannabinoids.

Methods: A cross-sectional primary data analysis of 101 young adults in Lexington, Kentucky to determine prevalence of lifetime novel cannabinoid use, past 30-day novel cannabinoid use, mode of use, motivation for use, and related demographic characteristics. Univariate and bivariate analysis were produced using the PROC …


Mccovid Campaign – A Social Media Implementation To Decrease Vaccine Hesitancy In Rural Counties, Harper Ford Jan 2024

Mccovid Campaign – A Social Media Implementation To Decrease Vaccine Hesitancy In Rural Counties, Harper Ford

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This capstone will explore the challenges of vaccine hesitancy, a continuously rising problem in the public health field. The focus is primarily on rural millennials in McCracken County, Kentucky. The study identifies key factors contributing to vaccine hesitancy including misinformation, trust issues, and the rapid development of the covid-19 vaccine. To address the above concerns the study proposes a targeted social media campaign using the health belief model to increase COVID-19 vaccine uptake through Facebook ads targeting millennials. The campaigns utilize the leverage of local insights and real-time data to enhance engagement and reduce hesitancy, focusing on adapting strategies based …


Environmental Justice In West Louisville, Ky, Ashley Wright Jan 2024

Environmental Justice In West Louisville, Ky, Ashley Wright

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

It is evident that West Louisville and Rubbertown are experiencing environmental exposures and related health impacts. It is important for environmental justice (EJ) areas like West Louisville and Rubbertown to gain increased awareness, due to EJ areas commonly being overlooked and forgotten about because of unjust treatment and lack of involvement. Furthermore, all of the data used for this project was publicly accessible. Community residents and the general public can access these data sources to identify which facilities are emitting toxins, as well as specific hazardous substances that are being released, the location of hazardous sites, cleanup status, and more. …


Improving Black Maternal Outcomes In Christian County, Ky: A Social Marketing Approach To Perinatal Provider Change, Ariel A. Arthur Jan 2024

Improving Black Maternal Outcomes In Christian County, Ky: A Social Marketing Approach To Perinatal Provider Change, Ariel A. Arthur

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Compared to other states in the country, Kentucky has historically poor population health outcomes. While the statewide maternal mortality rate is 16.1 per 100,000 live births, this statistic belies the stark racial disparities that exist. In 2018, the pregnancy-related death rate for Black women was 40.2 per 100,000 live births compared to 13.1 for White women. This pattern is persistent even after controlling for socioeconomic status, prenatal care, and other protective factors. Research shows that institutional and interpersonal racism when receiving obstetric care contributes to poor childbirth and postpartum outcomes for Black women. Additionally, geography and rural status may compound …


Implementation Of A Postpartum Depression Program In A Rural Kentucky County, Abby Cecil Jan 2024

Implementation Of A Postpartum Depression Program In A Rural Kentucky County, Abby Cecil

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This paper aims to describe the process of implementing a Postpartum Depression (PPD) prevention program in low-income women residing in rural communities. The paper describes the process of recruiting women in this population, where and how the program will be integrated into an existing clinic, and how the program will be sustained. PPD is a significant global public health problem that can be prevented and treated. The ROSE program (Reach Out, Stay Strong, Essentials for new mothers) is a series of classes that provide informational and social support to prevent PPD. This evidence-based program has been previously successful in reducing …


Increasing Hpv Vaccination In Two Appalachian Counties, Autumn Rice Jan 2024

Increasing Hpv Vaccination In Two Appalachian Counties, Autumn Rice

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

In response to the Funding Opportunity Announcement (FOA), the evidence-based Making Effective HPV Vaccine Recommendations training program will be implemented in the Southeast Kentucky AHEC region over the course of three years. The implementation of the Making Effective HPV Vaccine Recommendations program has three specific aims:

Aim 1: Effectively implement and deliver the Making Effective HPV Vaccine Recommendations program to immunization providers in the Southeast Kentucky AHEC region

Aim 2: Increase provider self-efficacy for making strong recommendations for HPV routinely

Aim 3: Increase the number of recommendations for the HPV vaccine among adolescents of Bell and Harlan Counties in Kentucky …


Patient Access To Glp-1 Ra’S: A Medicare Part D Policy Analysis, Celine Hummer Jan 2024

Patient Access To Glp-1 Ra’S: A Medicare Part D Policy Analysis, Celine Hummer

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This policy analysis examines the evolving landscape of GLP-1 receptor agonists (GLP-1 RAs) and their implications for Medicare Part D coverage. Initially developed for managing type 2 diabetes, GLP-1 RAs have rapidly gained popularity due to their efficacy in treating obesity and reducing cardiovascular events, leading to broader therapeutic applications. However, access to these medications under Medicare Part D is limited by high costs and coverage restrictions, particularly when used for obesity without diabetes. This analysis evaluates current Medicare Part D policies, including specialty drug tier placement, formulary restrictions, and the potential impact of recent legislative initiatives such as the …


Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson Jan 2024

Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson

Neurology Faculty Publications

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences.

METHODS: The National Alzheimer’s Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit.

RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who …


Navigating Asynchronous Online Learning: The Impacts Of Active Learning And Assigned Group Work On Student Motivation, Belonging, And Inclusion, Shea Elisabeth Carr Jan 2024

Navigating Asynchronous Online Learning: The Impacts Of Active Learning And Assigned Group Work On Student Motivation, Belonging, And Inclusion, Shea Elisabeth Carr

Theses and Dissertations--Biology

Motivation, belonging, and inclusion are all critical factors for student success but can be difficult to support in asynchronous online courses. Active learning and required group work have been shown to increase student motivation in in-person and synchronous online courses, but little is known about their impact in online asynchronous settings. This dissertation aimed to 1) evaluate the effect of active learning on student motivation in an online asynchronous setting and 2) evaluate the impact of assigned group work on student motivation and perceptions of belonging and inclusion within the context of an online, asynchronous physiology laboratory course. It was …


The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie Jan 2024

The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Oncogenic mutations activate secretory programs that drive tumor progression and represent therapeutic targets. The clinical relevance of CASPs is underscored by their prevalence, their linkages to specific genetic and epigenetic contexts, the proven efficacy of secretory blockade in preclinical models, and the availability of assays to identify vulnerable patient populations.


Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae Jan 2024

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …


Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak Jan 2024

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …


Effect Of Mitochondrial Oxidative Stress On Regulatory T Cell Manufacturing For Clinical Application In Transplantation: Results From A Pilot Study, Roberto Gedaly, Gabriel Orozco, Lillie J. Lewis, Deepa Valvi, Fanny Chapelin, Aman Khurana, Giovanna E. Hidalgo, Aaron Shmookler, Aashutosh Tripathi, Cuiping Zhang, Joseph B. Zwischenberger, Francesc Marti Jan 2024

Effect Of Mitochondrial Oxidative Stress On Regulatory T Cell Manufacturing For Clinical Application In Transplantation: Results From A Pilot Study, Roberto Gedaly, Gabriel Orozco, Lillie J. Lewis, Deepa Valvi, Fanny Chapelin, Aman Khurana, Giovanna E. Hidalgo, Aaron Shmookler, Aashutosh Tripathi, Cuiping Zhang, Joseph B. Zwischenberger, Francesc Marti

Markey Cancer Center Faculty Publications

The manufacturing process of regulatory T (Treg) cells for clinical application begins with the positive selection of CD25+ cells using superparamagnetic iron oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25–interleukin-2 receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with a concomitant decrease …


Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich Jan 2024

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …