Digital Commons Network^™

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

Plasma Metabolomics Analysis Of Aspirin Treatment And Risk Of Colorectal Adenomas, Elizabeth L Barry, Veronika Fedirko, Yutong Jin, Ken Liu, Leila A Mott, Janet L Peacock, Michael N Passarelli, John A Baron, Dean P Jones

Faculty, Staff and Student Publications

Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L Phan, Jacob H Elnaggar, Brianna Resendiz, Andrea Y Delgado Medrano, Erica J Lynn, Nicholas D Nguyen, Sonal S Noticewala, Geena G Mathew, Emma B Holliday, Bruce D Minsky, Prajnan Das, Van K Morris, Cathy Eng, Melissa P Mezzari, Joseph F Petrosino, Nadim J Ajami, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert

Faculty, Staff and Student Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Identifying Bone Matrix Impairments In A Mouse Model Of Neurofibromatosis Type 1 (Nf1) By Clinically Translatable Techniques, Rafay Ahmed, Sasidhar Uppuganti, Shrey Derasari, Joshua Meyer, Jacquelyn S Pennings, Florent Elefteriou, Jeffry S Nyman

Faculty, Staff and Students Publications

Three-to-four percent of children with neurofibromatosis type 1 (NF1) present with unilateral tibia bowing, fracture, and recalcitrant healing. Alkaline phosphatase enzyme therapy prevented poor bone mineralization and poor mechanical properties in mouse models of NF1 skeletal dysplasia; but transition to clinical trials is hampered by the lack of a technique that i) identifies NF1 patients at risk of tibia bowing and fracture making them eligible for trial enrollment and ii) monitors treatment effects on matrix characteristics related to bone strength. Therefore, we assessed the ability of matrix-sensitive techniques to provide characteristics that differentiate between cortical bone from mice characterized by …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Sex-Specific Phenotypes In The Aging Mouse Heart And Consequences For Chronic Fibrosis, Aude Angelini, Jesus Ortiz-Urbina, Joann Trial, Anilkumar K Reddy, Anna Malovannaya, Antrix Jain, Mark L Entman, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional …

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression For Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series, Momodou L Jammeh, Alexander Yang, Ahmmad A Abuirqeba, J Westley Ohman, Robert W Thompson

2020-Current year OA Pubs

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge.

OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS.

METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively.

RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 …

Experiences With Menses In Transgender And Gender Nonbinary Adolescents., Beth I. Schwartz, Arielle Effron, Benjamin Bear, Vanessa L Short, Julia Eisenberg, Sarah Felleman, Anne E Kazak

Department of Obstetrics and Gynecology Faculty Papers

STUDY OBJECTIVE: To describe menstrual history, associated dysphoria, and desire for menstrual management in transgender male and gender diverse adolescents who were assigned female at birth

DESIGN: Retrospective chart review

SETTING: Tertiary care children's hospital

PARTICIPANTS: All patients seen in a multidisciplinary pediatric gender program from March 2015 through December 2020 who were assigned female at birth, identified as transgender male or gender nonbinary, and had achieved menarche

INTERVENTION: None

MAIN OUTCOME MEASURES: Patient demographics, menstrual history, interest in and prior experiences with menstrual management, parental support, and concerns about menstrual management

RESULTS: Of the 129 included patients, 116 (90%) …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer's Disease., Jaclyn M Eissman, Logan Dumitrescu, Emily R Mahoney, Alexandra N Smith, Shubhabrata Mukherjee, Michael L Lee, Phoebe Scollard, Seo Eun Choi, William S Bush, Corinne D Engelman, Qiongshi Lu, David W Fardo, Emily H Trittschuh, Jesse Mez, Catherine C Kaczorowski, Hector Hernandez Saucedo, Keith F Widaman, Rachel F Buckley, Michael J Properzi, Elizabeth C Mormino, Hyun Sik Yang, Theresa M Harrison, Trey Hedden, Kwangsik Nho, Shea J Andrews, Douglas Tommet, Niran Hadad, R Elizabeth Sanders, Douglas M Ruderfer, Katherine A Gifford, Xiaoyuan Zhong, Neha S Raghavan, Badri N Vardarajan, Margaret A Pericak-Vance, Lindsay A Farrer, Li San Wang, Carlos Cruchaga, Gerard D Schellenberg, Nancy J Cox, Jonathan L Haines, C Dirk Keene, Andrew J Saykin, Eric B Larson, Reisa A Sperling, Richard Mayeux, Michael L Cuccaro, David A Bennett, Julie A Schneider, Paul K Crane, Angela L Jefferson, Timothy J Hohman

Faculty Research 2022

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer's Disease, Jaclyn M Eissman, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

An Updated Assessment Of 43,110 Patients Enrolled In The Childhood Cancer Research Network: A Children’S Oncology Group Report, Austin L Brown, Pagna Sok, Michael E Scheurer, Karen R Rabin, Erin L Marcotte, Douglas S Hawkins, Logan G Spector, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment.

Method: The number of US childhood patients with cancer diagnosed < 20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed-to-expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates.

Result: The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37-0.38]), non-Hispanics (0.35 [95% CI, 0.35-0.36]), and those diagnosed from 1 to 4 years …

The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated …

Psychiatric Symptoms Are Not Associated With Circulating Crp Concentrations After Controlling For Medical, Social, And Demographic Factors., Leandra K. Figueroa-Hall, Bohan Xu, Rayus Kuplicki, Bart N. Ford, Kaiping Burrows, T Kent Teague, Sandip Sen, Hung-Wen Yeh, Michael R. Irwin, Jonathan Savitz, Martin P. Paulus

Manuscripts, Articles, Book Chapters and Other Papers

Elevated serum concentrations (>3 mg/L) of the acute-phase protein, C-reactive protein (CRP), is used as a clinical marker of inflammation and is reported to be a strong risk factor for cardiovascular disease. In psychiatric populations, CRP concentration is reported to be higher in depressed versus healthy individuals. Positive associations between CRP and depression have been established in both clinical and community samples, but effect sizes are attenuated after controlling for confounding variables. Similarly, emerging research has begun to draw a link between inflammation, symptoms of anxiety, and substance abuse. Given the high level of comorbid anxiety and substance use …

Antibody Responses To Sars-Cov-2 After Infection Or Vaccination In Children And Young Adults With Inflammatory Bowel Disease., Joelynn Dailey, Lina Kozhaya, Mikail Dogan, Dena Hopkins, Blaine Lapin, Katherine Herbst, Michael Brimacombe, Kristen Grandonico, Fatih Karabacak, John Schreiber, Bruce Tsan-Liang Liang, Juan C Salazar, Derya Unutmaz, Jeffrey S Hyams

Faculty Research 2022

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and …

Socioeconomic Status And Gastric Cancer Surgical Outcomes: A National Cancer Database Study., Ryan Lamm, D Brock Hewitt, Michael Li, Adam C Powell, Adam C Berger

Department of Surgery Faculty Papers

INTRODUCTION: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Surgical resection is the gold standard of treatment. In the United States, race and socioeconomic status are associated with the diagnosis of GC; however, no studies have examined these as independent risk factors for surgical outcomes. Our study sought to investigate socioeconomic factors and GC surgical outcomes using a national cancer registry.

METHODS: GC patients between 2004 and 2016 were identified using the National Cancer Database. Univariate and multivariate logistic regression was used to analyze associations between socioeconomic factors and 30-d mortality, 90-d mortality, and unplanned readmission …

Disengagement Of Male Students In Remediated Ela Classes, Joanne Berardi Martin

Theses and Dissertations

The purpose of this action research was to examine the disengagement of male students in remediated English Language Arts (ELA) classes. Male students are disproportionately represented in remediated ELA classes, which indicates that male students are not progressing in their literacy skills at the same rate as females. Data was gathered from an ELA section of male students through a Google survey, a group interview, and two observations of students in a co-taught class. The purpose of these data collection methods was to understand the experiences of male students to determine the source of their disengagement. A focus group with …

Analysis Of Neonatal Neurobehavior And Developmental Outcomes Among Preterm Infants., Elisabeth C. Mcgowan, Julie A. Hofheimer, T Michael O'Shea, Howard Kilbride, Brian S. Carter, Jennifer Check, Jennifer Helderman, Charles R. Neal, Steve Pastyrnak, Lynne M. Smith, Marie Camerota, Lynne M. Dansereau, Sheri A. Della Grotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed.

Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes.

Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to …

White Coat Hypertension Persistence In Children And Adolescents: The Pediatric Nephrology Research Consortium Study, Yosuke Miyashita, Coral Hanevold, Anna Faino, Julia Scher, Marc Lande, Ikuyo Yamaguchi, Joel Hernandez, Alisa Acosta, Donald J Weaver, Jason Thomas, Mahmoud Kallash, Michael Ferguson, Ketan N Patel, Andrew M South, Megan Kelton, Joseph T Flynn

Faculty, Staff and Students Publications

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM.

STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We …

Effect Of Musculature On Mortality, A Retrospective Cohort Study, Amy L Shaver, Mary E Platek, Anurag K Singh, Sung Jun Ma, Mark Farrugia, Gregory Wilding, Andrew D Ray, Heather M Ochs-Balcom, Katia Noyes

Department of Medical Oncology Faculty Papers

Background: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early. The primary objective of this study was to determine if pre-treatment musculature was associated with all-cause mortality.

Methods: Patient demographic and clinical characteristics were abstracted from the cancer center electronic database (n = 403). Musculature was ascertained from pre-treatment CT scans. Propensity score matching was utilized to adjust for confounding …

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling To Promote Health And Longevity, Mahmoud Abdellatif, Tobias Pendl, Sebastian J Hofer, Moydul Islam, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Et Al

2020-Current year OA Pubs

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic …

Symptomatic, Clinical And Biomarker Associations For Mortality In Hospitalized Covid-19 Patients Enriched For African Americans, Hassan Ashktorab, Antonio Pizuorno, Folake Adeleye, Adeyinka Laiyemo, Maryam Mehdipour Dalivand, Farshad Aduli, Zaki A Sherif, Gholamreza Oskrochi, Kibreab Angesom, Philip Oppong-Twene, Suryanarayana Reddy Challa, Nnaemeka Okorie, Esther S Moon, Edward Romos, Boubini Jones-Wonni, Abdoul Madjid Kone, Sheldon Rankine, Camelita Thrift, Derek Scholes, Chiamaka Ekwunazu, Abigail Banson, Brianna Mitchell, Guttu Maskalo, Jillian Ross, Julencia Curtis, Rachel Kim, Chandler Gilliard, Geetha Ahuja, Joseph Mathew, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R. Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph B. Miller Md, Lakshmi Gayathri Chirumamilla, Fatimah Jackson, John M. Carethers, Farin Kamangar, Hassan Brim

Emergency Medicine Articles

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality.

METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected.

RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, …

Gut Dysbiosis And Age-Related Neurological Diseases In Females, Janelle M Korf, Bhanu P Ganesh, Louise D Mccullough

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Mentoring Urban African American Male Students In Secondary School, David Jacoby Collins

College of Education Theses and Dissertations

This narrative inquiry evaluated how a school-based mentorship program called The Chamber of Scholars: African American Male Mentoring Intervention, which served exclusively African American male students in high school, impacted the participants’ identification with academics, perception of mattering to their school, and academic performance. The program was evaluated using a pre-interview and a post-interview of all participants, daily field notes of activities, and weekly journals. The study found that participants who regularly attended daily intervention sessions for ten weeks increased their identification with academics (value of school). The study also found that participants who regularly attended daily intervention sessions for …

Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of

Tomatoes, Lycopene, And Prostate Cancer: What Have We Learned From Experimental Models?, Nancy E Moran, Jennifer M Thomas-Ahner, Lei Wan, Krystle E Zuniga, John W Erdman, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Human epidemiology suggests a protective effect of tomatoes or tomato phytochemicals, such as lycopene, on prostate cancer risk. However, human epidemiology alone cannot reveal causal relations. Laboratory animal models of prostate cancer provide opportunities to investigate hypotheses regarding dietary components in precisely controlled, experimental systems, contributing to our understanding of diet and cancer risk relations. We review the published studies evaluating the impact of tomatoes and/or lycopene in preclinical models of prostate carcinogenesis and tumorigenesis. The feeding of tomatoes or tomato components demonstrates anti-prostate cancer activity in both transplantable xenograft models of tumorigenesis and models of chemically- and genetically-driven carcinogenesis. …

Estrogen Hormone Is An Essential Sex Factor Inhibiting Inflammation And Immune Response In Covid-19, Fuhai Li, Adrianus C M Boon, Andrew P Michelson, Randi E Foraker, Ming Zhan, Philip R O Payne

Open Access Publications

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality of COVID-19 patients already infected with SARS-CoV-2. The global data on COVID-19 showed that men have a higher mortality rate than women. We further observed that the proportion of mortality of females increases starting from around the age of 55 significantly. Thus, sex is an essential factor associated with COVID-19 mortality, and sex related genetic factors could be interesting mechanisms and targets for COVID-19 treatment. However, the associated sex factors and signaling pathways remain unclear. Here, we propose …