Medicine and Health Sciences Commons^™

Amniotic Fluid-Derived Stem Cells: Potential Factories Of Natural And Mimetic Strategies For Congenital Malformations, Cristiane S R Fonteles, Julia Enterria-Rosales, Ying Lin, John W Steele, Ramiro A Villarreal-Leal, Jing Xiao, Daniel I Idowu, Beck Burgelin, Bogdan J Wlodarczyk, Richard H Finnell, Bruna Corradetti

Faculty, Staff and Students Publications

BACKGROUND: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.

METHODS: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion …

3d Genome Topology Distinguishes Molecular Subgroups Of Medulloblastoma, John J Y Lee, Michael J Johnston, Hamza Farooq, Huey-Miin Chen, Subhi Talal Younes, Raul Suarez, Melissa Zwaig, Nikoleta Juretic, William A Weiss, Jiannis Ragoussis, Nada Jabado, Michael D Taylor, Marco Gallo

Faculty, Staff and Students Publications

Four main medulloblastoma (MB) molecular subtypes have been identified based on transcriptional, DNA methylation, and genetic profiles. However, it is currently not known whether 3D genome architecture differs between MB subtypes. To address this question, we performed in situ Hi-C to reconstruct the 3D genome architecture of MB subtypes. In total, we generated Hi-C and matching transcriptome data for 28 surgical specimens and Hi-C data for one patient-derived xenograft. The average resolution of the Hi-C maps was 6,833 bp. Using these data, we found that insulation scores of topologically associating domains (TADs) were effective at distinguishing MB molecular subgroups. TAD …

A Review Of The Association Between Dietary Intake And Brain Iron Levels In Older Adults: Preliminary Findings And Future Directions., Valentinos Zachariou, Christopher E. Bauer, Colleen A. Pappas, Brian T. Gold

Behavioral Science Faculty Publications

Background/Objectives: Non-heme iron is essential for critical neuronal functions such as ATP generation, synaptogenesis, neurotransmitter synthesis, and myelin formation. However, as non-heme iron accumulates with age, excessive levels can contribute to oxidative stress, potentially disrupting neuronal integrity and contributing to cognitive decline. Despite growing evidence linking high brain iron with poorer cognitive performance, there are currently no proven methods to reduce brain iron accumulation in aging or to protect cognitive function from iron’s negative effects. Recent studies suggest that nutrition may influence brain iron levels, though the evidence remains limited and mixed. Methods: In this review, we explore recent findings, …

Alzheimer's Disease-Linked Risk Alleles Elevate Microglial Cgas-Associated Senescence And Neurodegeneration In A Tauopathy Model, Gillian K Carling, Xiaoying Chen, David M Holtzman, Et Al.

2020-Current year OA Pubs

The strongest risk factors for late-onset sporadic Alzheimer's disease (AD) include the ε4 allele of apolipoprotein E (APOE), the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 and TREM2

Diet And Immune Effects Trial (Diet)- A Randomized, Double-Blinded Dietary Intervention Study In Patients With Melanoma Receiving Immunotherapy, Rachel M Farias, Yan Jiang, Erma J Levy, Cindy Hwang, Jian Wang, Elizabeth M Burton, Lorenzo Cohen, Nadim Ajami, Jennifer A Wargo, Carrie R Daniel, Jennifer L Mcquade

Faculty, Staff and Student Publications

Background: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and …

Functional Connectivity Biomarker Extraction For Schizophrenia Based On Energy Landscape Machine Learning Techniques, Janerra D Allen, Sravani Varanasi, Fei Han, L Elliot Hong, Fow-Sen Choa

Faculty, Staff and Student Publications

Brain connectivity represents the functional organization of the brain, which is an important indicator for evaluating neuropsychiatric disorders and treatment effects. Schizophrenia is associated with impaired functional connectivity but characterizing the complex abnormality patterns has been challenging. In this work, we used resting-state functional magnetic resonance imaging (fMRI) data to measure functional connectivity between 55 schizophrenia patients and 63 healthy controls across 246 regions of interest (ROIs) and extracted the disease-related connectivity patterns using energy landscape (EL) analysis. EL analysis captures the complexity of brain function in schizophrenia by focusing on functional brain state stability and region-specific dynamics. Age, sex, …

Trajectory, Interactions, And Predictors Of Higher Symptom Burden During Induction Therapy For Multiple Myeloma, Mona Kamal, Qiuling Shi, Shu-En Shen, Charles Cleeland, Xin Shelley Wang

Faculty, Staff and Student Publications

Background: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

The Use Of Cloud Based Machine Learning To Predict Outcome In Intracerebral Haemorrhage Without Explicit Programming Expertise, Ajay Hegde, Deepu Vijaysenan, Pitchaiah Mandava, Girish Menon

Faculty, Staff and Students Publications

Machine Learning (ML) techniques require novel computer programming skills along with clinical domain knowledge to produce a useful model. We demonstrate the use of a cloud-based ML tool that does not require any programming expertise to develop, validate and deploy a prognostic model for Intracerebral Haemorrhage (ICH). The data of patients admitted with Spontaneous Intracerebral haemorrhage from January 2015 to December 2019 was accessed from our prospectively maintained hospital stroke registry. 80% of the dataset was used for training, 10% for validation, and 10% for testing. Seventeen input variables were used to predict the dichotomized outcomes (Good outcome mRS 0-3/ …

Nt-Probnp And Cardiac Troponin I, But Not Cardiac Troponin T, Are Associated With 7-Year Changes In Cardiac Structure And Function In Older Adults: The Aric Study, Peder L Myhre, Brian Claggett, Christie M Ballantyne, Ron C Hoogeveen, Elizabeth Selvin, Kunihiro Matsushita, Dalane Kitzman, Suma Konety, Thomas Mosley, Amil M Shah

Faculty, Staff and Students Publications

Background: Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized.

Methods: Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and …

Prenatal Assessment Of Brain Malformations On Neuroimaging: An Expert Panel Review, Ivana Pogledic, Kshitij Mankad, Mariasavina Severino, Tally Lerman-Sagie, Andras Jakab, Efrat Hadi, Anna C Jansen, Nadia Bahi-Buisson, Natalya Di Donato, Renske Oegema, Christian Mitter, Ivan Capo, Matthew T Whitehead, Parthiv Haldipur, Grazia Mancini, Thierry A G M Huisman, Andrea Righini, Bill Dobyns, James A Barkovich, Natasa Jovanov Milosevic, Gregor Kasprian, Maarten Lequin

Faculty, Staff and Students Publications

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel review is written with the central aim of providing an easy-to-understand road map to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. For every developmental stage, the utility of each available neuroimaging modality, including prenatal multiplanar neuro sonography, anatomical MRI and advanced MRI techniques, as …

Redesigning The Hospital Environment To Improve Restfulness, Caellagh D Catley, Kayla Paynter, Kendall Jackson, Ashley Huggins, Jenny Ji, Sai Anusha Sanka, Michelle Simkins, Thomas M Maddox, Patrick G Lyons

2020-Current year OA Pubs

IMPORTANCE: Hospital wards are often not conducive to patient sleep, negatively affecting patient health and experience.

OBJECTIVES: To assess determinants of in-hospital restfulness and to design and test rest-promoting interventions on the wards in partnership with clinicians, staff, and patients.

DESIGN, SETTING, AND PARTICIPANTS: This rapid-sequential mixed-methods quality improvement study was performed at a large urban academic hospital in St Louis, Missouri, from May 1, 2021, to December 31, 2022, with follow-up through hospitalization. Mixed-methods activities involved purposively selected hospitalized adults on the wards, nurses, hospitalists, and hospital staff. Interventions included all adult hospitalizations on the study wards.

INTERVENTIONS: Sequential …

Secure Messaging Use And Wrong-Patient Ordering Errors Among Inpatient Clinicians, Sunny S Lou, Daphne Lew, Linlin Xia, Laura Baratta, Elise Eiden, Thomas Kannampallil

2020-Current year OA Pubs

IMPORTANCE: Use of secure messaging for clinician-to-clinician communication has increased exponentially over the past decade, but its association with clinician work is poorly understood.

OBJECTIVE: To investigate the association between secure messaging use and wrong-patient ordering errors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included inpatient attending physicians, trainee physicians, and advanced practice practitioners (APPs) from 14 academic and community hospitals. Secure messaging volume was assessed over a 3-month period (February 1 to April 30, 2023).

EXPOSURE: Secure messaging volume per clinician-day, measured as the count of secure messages sent and received by a clinician on a given clinician-day.

MAIN …

Medical And Surgical Episodes Among Hospital Participants In The Bundled Payments For Care Improvement-Advanced Program, Keenan J Robbins, Jie Zheng, R J Waken, E John Orav, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Hospital participation in the Bundled Payments for Care Improvement-Advanced (BPCI-A) initiative has been associated with modest savings and stable clinical outcomes overall, but it is unknown whether the program performs differently for medical and surgical or procedural (henceforth, surgical) episodes.

OBJECTIVE: To assess the association of BPCI-A participation with Medicare spending and clinical outcomes for medical and surgical episodes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective difference-in-differences cohort study utilized 100% Medicare fee-for-service inpatient claims for episodes initiated between January 1, 2017, and September 30, 2019, and included 90 days of follow-up. The setting was hospitals participating in BPCI-A and …

A Preoperative Window-Of-Opportunity Study Of Oral Serd, Imlunestrant, In Newly Diagnosed Er-Positive, Her2-Negative Early Breast Cancer: Results From The Ember-2 Study, Patrick Neven, Rebecca Aft, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study.

PATIENTS AND METHODS: Postmenopausal women with untreated, operable estrogen receptor (ER)-positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired …

Heterozygous Btnl8 Variants In Individuals With Multisystem Inflammatory Syndrome In Children (Mis-C), Evangelos Bellos, Erica G Schmitt, Et Al.

2020-Current year OA Pubs

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

Neuroanatomical Variability And Substance Use Initiation In Late Childhood And Early Adolescence, Alex P Miller, David A A Baranger, Sarah E Paul, Hugh Garavan, Scott Mackey, Susan F Tapert, Kimberly H Leblanc, Arpana Agrawal, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood.

OBJECTIVE: To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, …

A Latent Class Assessment Of Healthcare Access Factors And Disparities In Breast Cancer Care Timeliness, Matthew Dunn, Didong Li, Marc Emerson, Caroline Thompson, Hazel Nichols, Sarah Van Alsten, Mya Roberson, Stephanie Wheeler, Lisa Carey, Terry Hyslop, Jennifer Elston Lafata, Melissa Troester

Kimmel Cancer Center Faculty Papers

BACKGROUND: Delays in breast cancer diagnosis and treatment lead to worse survival and quality of life. Racial disparities in care timeliness have been reported, but few studies have examined access at multiple points along the care continuum (diagnosis, treatment initiation, treatment duration, and genomic testing).

METHODS AND FINDINGS: The Carolina Breast Cancer Study (CBCS) Phase 3 is a population-based, case-only cohort (n = 2,998, 50% black) of patients with invasive breast cancer diagnoses (2008 to 2013). We used latent class analysis (LCA) to group participants based on patterns of factors within 3 separate domains: socioeconomic status ("SES"), "care barriers," and …

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …

Comparative Analysis Of Indices For Social Determinants Of Health In Pediatric Surgical Populations, Caroline Q Stephens, Ava Yap, Lan Vu, Jacqueline M Saito, Dwight Barry, Amy M Shui, Hannah Cockrell, Sarah Cairo, Derek Wakeman, Loren Berman, Sarah Greenberg, Allison F Linden, Jonathan Kohler, Kuojen Tsao, Nicole A Wilson

Faculty, Staff and Student Publications

Importance: Conclusions vary substantially among studies examining associations between area-based social determinants of health (SDOH) and pediatric health disparities based on the selected patient population and SDOH index. Most national studies use zip codes, which encompass a wide distribution of communities, limiting the generalizability of findings.

Objectives: To characterize the distributions of composite SDOH indices for pediatric surgical patients within a national sample of academic children's hospitals and to assess SDOH index precision in classifying patients at similar levels of disadvantage.

Design, setting, and participants: This multicenter retrospective cohort study included patients younger than 18 years who underwent surgery from …

Private-Sector Readmissions For Inpatient Surgery In Veterans Health Administration Hospitals, Mary Vaughan Sarrazin, Yubo Gao, Carly A Jacobs, Michael A Jacobs, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Andrea L Strayer, John Cashy, George Wehby, Paula K Shireman, Daniel E Hall

Faculty, Staff and Student Publications

Importance: The Veterans Health Administration (VHA) reports multiple indicators of hospital surgical performance, including hospital risk-standardized 30-day readmission rates (RSRRs). Currently, most routinely reported measures do not include readmissions that occur outside VHA hospitals. The impact of readmissions outside the VHA on hospital RSRR is not known.

Objective: To measure the impact of including non-VHA readmissions on VHA hospital performance rankings for 30-day readmission.

Design, setting, and participants: This retrospective cohort study included patients aged at least 65 years from 2013 to 2019 from the Veterans Affairs Surgical Quality Improvement Program linked to patient-level data from the VHA and Medicare. …

Myeloid Activation Clears Ascites And Reveals Il27-Dependent Regression Of Metastatic Ovarian Cancer, Brennah Murphy, Taito Miyamoto, Bryan S Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P Zhu, Daniel T Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang

Faculty, Staff and Student Publications

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of < 30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

Individualized Functional Magnetic Resonance Imaging Neuromodulation Enhances Visuospatial Perception: A Proof-Of-Concept Study, Anthony Allam, Vincent Allam, Sandy Reddy, Eric M Rohren, Sameer A Sheth, Emmanouil Froudarakis, T Dorina Papageorgiou

Duncan NRI Faculty and Staff Publications

This proof-of-concept study uses individualized functional magnetic resonance imaging neuromodulation (iNM) to explore the mechanisms that enhance BOLD signals in visuospatial perception (VP) networks that are crucial for navigation. Healthy participants (n = 8) performed a VP up- and down-direction discrimination task at full and subthreshold coherence through peripheral vision, and superimposed direction through visual imagery (VI) at central space under iNM and control conditions. iNM targets individualized anatomical and functional middle- and medial-superior temporal (MST) networks that control VP. We found that iNM engaged selective exteroceptive and interoceptive attention (SEIA) and motor planning (MP) networks. Specifically, iNM increased …

Onset And Progression Of Disease In Nonhuman Primates With Pde6c Cone Disorder, Monica Ardon, Lily Nguyen, Rui Chen, Jeffrey Rogers, Tim Stout, Sara Thomasy, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: The California National Primate Research Center contains a colony of rhesus macaques with a homozygous missense mutation in PDE6C (R565Q) which causes a cone disorder similar to PDE6C achromatopsia in humans. The purposes of this study are to characterize the phenotype in PDE6C macaques in detail to determine the onset of the cone phenotype, the degree to which the phenotype progresses, if heterozygote animals have an intermediate phenotype, and if rod photoreceptor function declines over time.

METHODS: We analyzed spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and electroretinography (ERG) data from 102 eyes of 51 macaques (aged 0.25 …

The Study Of The Epidemiology Of Pediatric Hypertension Registry (Superhero): Rationale And Methods, Andrew M South, Victoria C Giammattei, Kiri W Bagley, Christine Y Bakhoum, William H Beasley, Morgan B Bily, Shupti Biswas, Aaron M Bridges, Rushelle L Byfield, Jessica Fallon Campbell, Rahul Chanchlani, Ashton Chen, Lucy D'Agostino Mcgowan, Stephen M Downs, Gina M Fergeson, Jason H Greenberg, Taylor A Hill-Horowitz, Elizabeth T Jensen, Mahmoud Kallash, Margret Kamel, Stefan G Kiessling, David M Kline, John R Laisure, Gang Liu, Jackson Londeree, Caroline B Lucas, Sai Sudha Mannemuddhu, Kuo-Rei Mao, Jason M Misurac, Margaret O Murphy, James T Nugent, Elizabeth A Onugha, Ashna Pudupakkam, Kathy M Redmond, Sandeep Riar, Christine B Sethna, Sahar Siddiqui, Ashley L Thumann, Stephen R Uss, Carol L Vincent, Irina V Viviano, Michael J Walsh, Blanche D White, Robert P Woroniecki, Michael Wu, Ikuyo Yamaguchi, Emily Yun, Donald J Weaver

Faculty, Staff and Students Publications

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th …

Urinary Metal Levels, Cognitive Test Performance, And Dementia In The Multi-Ethnic Study Of Atherosclerosis, Arce Domingo-Relloso, Katlyn E Mcgraw, Susan R Heckbert, Jose A Luchsinger, Kathrin Schilling, Ronald A Glabonjat, Irene Martinez-Morata, Melanie Mayer, Yongmei Liu, Alexis C Wood, Jeff Goldsmith, Kathleen M Hayden, Mohamad Habes, Ilya M Nasrallah, R Nick Bryan, Tanweer Rashid, Wendy S Post, Jerome I Rotter, Priya Palta, Linda Valeri, Timothy M Hughes, Ana Navas-Acien

Faculty, Staff and Students Publications

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024.

EXPOSURE: Urine samples were collected at baseline …

Chlorthalidone Vs Hydrochlorothiazide And Kidney Outcomes In Patients With Hypertension: A Secondary Analysis Of A Randomized Clinical Trial, Areef Ishani, Cynthia Hau, Srihari Raju, Jessica K Wise, Peter A Glassman, Addison A Taylor, Ryan E Ferguson, William C Cushman, Sarah M Leatherman

Faculty, Staff and Students Publications

Importance: Hypertension is a risk factor for the development and progression of chronic kidney disease (CKD). It is unclear whether different thiazide diuretics have a differential impact on kidney outcomes.

Objective: To compare kidney outcomes in patients with hypertension taking chlorthalidone and hydrochlorothiazide.

Design, setting, and participants: This prespecified secondary analysis of the Diuretic Comparison Project, a randomized clinical trial comparing chlorthalidone and hydrochlorothiazide for the treatment of hypertension, was conducted between June 1, 2016, and June 1, 2022, through Veterans Affairs facilities nationwide. This analysis extended follow-up to December 31, 2023. Veterans 65 years or older with hypertension who …

Neurofeedback: New Territories And Neurocognitive Mechanisms Of Endogenous Neuromodulation, James Sulzer, T Dorina Papageorgiou, Rainer Goebel, Talma Hendler

Faculty, Staff and Students Publications

Neurofeedback (NF) is endogenous neuromodulation of circumscribed brain circuitry. While its use of real-time brain activity in a closed-loop system is similar to brain-computer interfaces, instead of controlling an external device like the latter, the goal of NF is to change a targeted brain function. In this special issue on NF, we present current and future methods for extracting and manipulating neural function, how these methods may reveal new insights about brain function, applications, and rarely discussed ethical considerations of guiding and interpreting the brain activity of others. Together, the articles in this issue outline the possibilities of NF use …

Excess Mortality In Persons With Concurrent Hiv And Cancer Diagnoses: A Retrospective Cohort Study, Kamaria L Lee, Varada Sarovar, Jennifer O Lam, Wendy A Leyden, Stacey E Alexeeff, Alexandra N Lea, Rulin C Hechter, Haihong Hu, Julia L Marcus, Qing Yuan, Jennifer R Kramer, Lilie L Lin, Elizabeth Y Chiao, William J Towner, Michael A Horberg, Michael J Silverberg

Center for Medical Ethics and Health Policy Staff Publications

Background: With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality among PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population.

Methods: We identified 39,000 PWH and 387,767 demographically matched PWoH in three integrated healthcare systems from 2000 to 2016. We estimated excess mortality among PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus-, and …

Major Depressive Disorder And Driving Behavior Among Older Adults, Ganesh M Babulal, Ling Chen, Jean-Francois Trani, David C Brown, David B Carr, Beau M Ances, Eric J Lenze, Drives Project

2020-Current year OA Pubs

IMPORTANCE: Depression and antidepressant use are independently associated with crash risk among older drivers. However, it is unclear what factors impact daily driving that increase safety risk for drivers with depression.

OBJECTIVE: To examine differences in naturalistic driving behavior and safety between older adults with and without major depressive disorder (MDD).

DESIGN, SETTING, AND PARTICIPANTS: A prospective longitudinal cohort study was conducted among older adults (≥65 years) from the Driving Real-World In-Vehicle Evaluation System Project collected from July 1, 2021, to December 30, 2023. The sample included 85 participants with MDD and 310 participants without. Neurological, clinical, mood, and neuropsychological …