Digital Commons Network^™

Short-Term Health And Safety Outcomes Associated With Digital Hotline Use At Interpersonal Violence-Focused Agencies, Leila Wood, Elizabeth Baumler, Rachel J Voth Schrag, Aly Kramer Jacobs, Jeff R Temple, Erin Clark

Faculty, Staff and Student Publications

Community organizations strive to help survivors of intimate partner violence (IPV), stalking, sexual assault and human trafficking address health and safety needs. Hotline, offered by local agencies, is the first line of support for survivors to address needs. Increasingly, hotline is offered in digital formats (chat and text) to meet the emergent needs of survivors. Despite the growing use of digital hotline, little is known about short-term health and safety changes associated with use. Partnering with 2 local agencies in a Southern state, we recruited first-time digital hotline participants to an online baseline and follow-up (6 weeks later) assessment (n …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

Psychosocial Impacts Of Non-Fatal Firearm Injuries On Youth: Findings From A Qualitative Study, Annalyn S Demello, Jeff R Temple, Liam De Vassal, Irma Alvarado, Angela Waguespack, Monique R Pappadis, Jong O Lee, Leila G Wood

Faculty, Staff and Student Publications

Most adolescents and young adult victims of firearm violence survive, yet the mental and behavioral health outcomes associated with these incidents remain understudied. Given the potential for recurrent violence victimization and long-term psychosocial sequela after being shot, understanding the experiences of firearm injury survivors is a critical area for development. We conducted a qualitative study to explore the development of attitudes, describe psychosocial consequences, and contextualize behavioral and social outcomes among young, gunshot wounded (GSW) patients from a Level 1 trauma center in southeast Texas. A retrospective chart review and prospective recruitment of GSW patients aged 15 to 29 years …

Risk Factors For Diagnostic Change From Glaucoma Suspect To Primary Open-Angle Glaucoma And Vice Versa Over 2 Years, Lillian K To, Nicole V Carrabba, Chaitanya G Kalathuru, Alice Z Chuang, Logan Smith, Robert M Feldman

Faculty, Staff and Student Publications

Objective: This study investigates the incidence and causes of diagnostic changes from primary open-angle glaucoma suspect (POAGS) to primary open-angle glaucoma (POAG), and vice versa, in clinical practice.

Design: This is a retrospective, single-site, case-control study.

Participants: It includes patients > 40 years of age diagnosed with either POAG or POAGS between 2013 and 2020. Controls had a minimum of 24 months of follow-up without a diagnostic change, whereas cases underwent a diagnostic change from glaucoma to suspect (POAG to POAGS) or from suspect to glaucoma (POAGS to POAG) within 2 years.

Methods: At initial and follow-up visits, diagnosis, treatment, type …

Analyzing Practice Pattern In Treating Partial-Thickness Rotator Cuff Tears: A Dual Perspective From National Database And American Shoulder And Elbow Surgeons Parcial Research Group, H Mike Kim, Emily Leary, Champ L Baker, Leslie A Barnes, R Alexander Creighton, Frances Cuomo, Matthew J Dipaola, Abdullah Foad, James M Gregory, Brian F Grogan, Scott G Kaar, Eitan M Kohan, Sumant G Krishnan, Eddie Y Lo, John T Moor, Parcial Group Contributors

Faculty, Staff and Student Publications

Background: Partial-thickness rotator cuff tears (PTRCTs), often considered less severe than full-thickness rotator cuff tears (FTRCTs), can be equally symptomatic. Despite the prevalence of PTRCTs, scholarly attention has predominantly focused on FTRCTs, resulting in a relative neglect of PTRCTs. This study aimed to assess the incidence of surgical repairs for PTRCTs in the United States (U.S.) using the Nationwide Ambulatory Surgery Sample (NASS) database and delineate practice patterns among a group of American Shoulder and Elbow Surgeons (ASES) members.

Methods: The NASS database, representing approximately 67% of U.S. ambulatory surgical encounters, was queried to obtain the incidence of PTRCT and …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

Development Of An H&E On-Block Staining Technique For Collagen Detection In Cryo-Fluorescence Tomography Imaging Of Frozen Breast Tissue Samples, Erin P Snoddy, Tien T Tang, Natalie Fowlkes, Thomas Huynh, Kari J Brewer Savannah, Alejandro Contreras, Gregory Reece, Kristy K Brock

Faculty, Staff and Student Publications

Hematoxylin and eosin (H&E) staining is widely considered to be the gold-standard diagnostic tool for histopathology evaluation. However, the fatty nature of some tissue types, such as breast tissue, presents challenges with cryo-sectioning, often resulting in artifacts that can make histopathologic interpretation and correlation with other imaging modalities virtually impossible. We present an optimized on-block H&E staining technique that improves contrast for identifying collagenous stroma during cryo-fluorescence tomography (CFT) sectioning. In this prospective study, we embedded four breast specimens with confirmed ligaments from a bilateral mastopexy in an optimal cutting temperature block. Two of the samples were processed on a …

Wnt7a, Naomi M Calhoun, Richard R Behringer

Faculty, Staff and Student Publications

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

Disparities In Breast Cancer Detection Modalities And Outcomes Among Geriatric Female Cancer Patients, Zhaoli Liu, Mathilda Nicot-Cartsonis, Biai D E Digbeu, Daoqi Gao, Sharon H Giordano, Yong-Fang Kuo

Faculty, Staff and Student Publications

This study examined racial and geographic disparities in breast cancer detection modalities (screening-, diagnostic-, or non-mammography) with cancer stage and mortality. A retrospective cohort study was conducted using Texas Cancer Registry-Medicare linkage data for geriatric women. Cancers detected through screening and diagnostic mammography had 43 % (95 % CI, 39 %-46 %, p < .0001) and 31 % (95 % CI, 27 %-35 %, p < .0001) lower all-cause mortality, and 49 % (95 % CI, 41 %-54 %, p < .0001) and 37 % (95 % CI, 32 %-43 %, p < .0001) lower cancer-specific mortality, respectively, compared to non-mammography-detected breast cancers. Patients from rural areas were 17 % (95 % CI, 1.06 - 1.29) more likely to be diagnosed with mid- (p = .0023) and advanced stage (p = .003) cancers compared to their urban counterparts. Racial or geographic disparities in cancer detection modalities with associated mortality no longer exist after adjusting for covariates. Healthcare professionals can leverage these findings to promote rural cancer health equity.

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Effects Of Cognitive Rehabilitation And Exercise On Brain Structure In Progressive Multiple Sclerosis: Results From The Cogex Trial, Cogex Research Team, Francesco Romanò, Maria A. Rocca, Elisabetta Pagani, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D. Chiaravalloti, Gary Cutter, Ulrik Dalgas, John Deluca, Rachel Farrell, Peter Feys, Jennifer Freeman, Matilde Inglese, Emilio Cipriano, Cecilia Meza, Robert W. Motl, Amber Salter, Brian M. Sandroff, Anthony Feinstein, Massimo Filippi

School of Health Professions

Background: We previously showed increased cortical grey matter (GM) volume in CogEx trial participants who performed cognitive rehabilitation (CR). Here, we explore combined CR and aerobic exercise (EX) effects on regional changes in brain volumes and white matter (WM) integrity. Methods: Seventy-three patients were randomized into four groups receiving a combination of CR and EX or their sham versions: CR + EX, CR + EX-sham, EX + CR-sham, and CR-sham + EX-sham. A diagnosis of progressive multiple sclerosis (PMS) and impaired information processing speed were required for inclusion. Participants attended a 12-week intervention twice/week. Assessments were performed at baseline, week-12 …

Edible Algae Reduce Blood Pressure In Humans: A Systematic Review And Meta-Analysis Of Randomised Controlled Trials, Patricia Casas-Agustench, Sandra Mínguez, Zoe Brookes, Raul Bescos

School of Health Professions

BACKGROUND: Edible algae contain bioactive compounds such as peptides, fucoidan, polyphenols, potassium, omega-3 fatty acids, and antioxidants that may benefit cardiovascular health, particularly in lowering blood pressure (BP) regulation. Certain species, including Nori and Kelp, are also rich in inorganic nitrate, known for its BP-lowering effects. However, the relationship between algae consumption and hypertension remains controversial. This study evaluated the effects of edible algae on BP in humans, considering factors such as algae type, format, dosage, intervention duration, health status, and baseline BP.

METHODS: A systematic search of Medline-Pubmed, Scopus and Cochrane databases was conducted through December 2024. Randomised controlled …

Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Materials and methods

Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee

Journal Articles: Cellular & Integrative Physiology

Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-Prkdc^scidIl2rgt^m1Wjl/SzJ humanized mice (Hu-mice) infected with HIV-1_ADA and treated for 13 weeks with dolutegravir …

Delayed Hypertension Diagnosis And Its Association With Cardiovascular Treatment And Outcomes, Yuan Lu, John E. Brush Jr, Chungsoo Kim, Yuntian Liu, Xin Xin, Chenxi Huang, Mitsuaki Sawano, Patrick Young, Jacob Mcpadden, Mark Anderson, John S. Burrows, Jordan R. Asher, Harlan M. Krumholz

Department of Medicine Faculty Publications

Importance Hypertension is a major risk factor for cardiovascular disease, yet delays in diagnosis may limit timely treatment initiation and increase cardiovascular risk.

Objectives To examine the timing of clinical hypertension diagnosis, its association with antihypertensive medication prescribing, and its association with long-term cardiovascular outcomes.

Design, Setting, and Participants This retrospective cohort study analyzed electronic health record (EHR) data from an integrated health care system. Adults aged 18 to 85 years with at least 2 outpatient blood pressure (BP) readings of 140/90 mm Hg or more recorded at least 30 days apart from January 1, 2010, to December 31, 2021, …

Group Antenatal Care Positively Transforms The Care Experience: Results Of An Effectiveness Trial In Malawi, Crystal L. Patil, Kathleen F. Noor, Esnath Kapito, Li C. Liu, Xiaohan Mei, Elizabeth Chodzaza, Genesis Chorwe-Sungani, Ursula Kafuulafula, Elizabeth T. Abrams, Allissa Desloge, Ashley Gresh, Rohan D. Jeremiah, Dhruvi R. Patel, Anne Batchelder, Heidy Wang, Jocelyn Faydenko, Sharon S. Rising, Ellen Chirwa

Department of Medicine Faculty Publications

Background

We developed and tested a Centering-based group antenatal (ANC) model in Malawi, integrating health promotion for HIV prevention and mental health. We present effectiveness data and examine congruence with only the Group ANC theory of change model, which identifies key processes as supportive relationships, empowered partners in learning and care, and meaningful services, leading to better ANC experiences and outcomes.

Methods

We conducted a hybrid effectiveness-implementation trial at seven clinics in Blantyre District, Malawi, comparing outcomes for 1887 pregnant women randomly assigned to Group ANC or Individual ANC. Group effects on outcomes were summarized and evaluated using t-tests, Mann-Whitney, …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Preferences And Feasibility Of Long-Acting Technologies For The Treatment Of Hepatitis C Virus: A Survey Of Patients In Diverse Low- And Middle-Income Countries, Renae Furl, Kimberly Scarsi, Harlan Sayles, Matt Anderson, Joelle Dountio Ofimboudem, Ethel D. Weld, Imam Waked, Asmaa Gomaa, Alzhraa Al-Khatib, Fatma Mohammed Elshobary, Hailemichael Desalegn, Henok Fisseha, Sunil Solomon, Shruti Mehta, Andrew Owen, Steve Rannard, David L. Thomas, Susan Swindells

Journal Articles: Infectious Diseases

Despite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low- and middle-income countries (LMICs). Long-acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA-HCV treatment across three LMICs: Egypt, Ethiopia and India. The survey focused on understanding barriers and facilitators to treatment, with emphasis on LA treatment preferences. Four-hundred respondents completed a survey including demographics, HCV treatment history and preferences for injections, implants and microarray patches (MAPs) compared to pills. Overall, 78% of respondents were willing to receive injections, 43% were willing to receive implants and …

Efficacy And Safety Of 4-Month Rifapentine-Based Tuberculosis Treatments In Persons With Diabetes., Ekaterina V. Kurbatova, William C. Whitworth, Lakshmi Praveena Peddareddy, Patrick P. J. Phillips, Nigel A. Scott, Kia E. Bryant, Rodney Dawson, Sandra Wagner Cardoso, Wadzanai Samaneka, Melissa Engle, Ziyaad Waja, Erin Sizemore, Wendy Carr, Kelly E. Dooley, Radojka Savic, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Nhung V. Nguyen, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and …

Pregnancy Outcomes After Exposure To Tuberculosis Treatment In Phase 3 Clinical Trial, 2016-2020, Ekaterina V. Kurbatova, William C. Whitworth, Kia E. Bryant, Meredith G. Dixon, Kelly E. Dooley, Nigel A. Scott, Rosanna Boyd, Nicole E. Brown, Kimberley N. Chapman Hedges, Wendy Carr, Lakshmi P. Peddareddy, Grace Muzanyi, Rodney Dawson, Ziyad Waja, Neil Martinson, Jyoti S. V. Mathad, Payam Nahid, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Patrick P. J. Phillips, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We analyzed pregnancy outcomes of women who became pregnant during the study. Among 740 women, 97 (13.1%) became pregnant. Of 102 pregnancies (in 97 participants), 30 (29.4%) participants were exposed to study drugs. Fetal loss was reported for 3/13 (23.1%) in the control regimen, 1/9 (11.1%) in the rifapentine/moxifloxacin regimen, and 1/8 (12.5%) in the rifapentine regimen. Among 21 live births in exposed pregnancies (7 in each arm), 1 infant with a congenital anomaly was reported in a participant on the …

Patterns Of Intra-Cluster Correlation Coefficients In School-Based Cluster Randomised Controlled Trials Of Interventions For Improving Social-Emotional Functioning Outcomes In Pupils: A Secondary Data Analysis Of Five Uk-Based Studies, Kitty Parker, Michael Nunns, Zhi Min Xiao, Tamsin Ford, Paul Stallard, Willem Kuyken, Nick Axford, Obioha C. Ukoumunne

Peninsula Medical School

Background: The cluster randomised trial (CRT) design is increasingly used to evaluate the impact of school-based interventions for improving social-emotional functioning outcomes in pupils. Good knowledge is required on plausible values of the intra-cluster correlation coefficient (ICC) of the outcome to calculate the required sample size in such studies. Using data from five school-based CRTs in the UK, we estimate, and describe patterns in, ICCs for social-emotional functioning outcomes. Methods: Mixed effects linear regression models were fitted to estimate the ICC and variance components. Estimates for baseline data were obtained by fitting “null” models that had no predictor variables; estimates …

Multiplex Lateral Flow Test Sensitivity And Specificity In Detecting Influenza A, B And Sars-Cov-2 In Adult Patients In A Uk Emergency Department, Rahul Batra, Edward Blandford, Raghavendran Kulasegaran-Shylini, Matthias E Futschik, Abbie Bown, Matthew Catton, Hermione Conti-Frith, Alexandra Alexandridou, Rebecca Gill, Clara Milroy, Sean Harper, Holly Gettings, Maryann Noronha, Hooi-Ling Harrison, Sam Douthwaite, Gaia Nebbia, Paul E Klapper, Sarah Tunkel, Richard Vipond, Susan Hopkins, Tom Fowler

School of Biomedical Sciences

BACKGROUND: Rapid identification of individuals with acute respiratory infections is crucial for preventing nosocomial infections. For rapid diagnosis, especially in EDs, lateral flow devices (LFDs) are a convenient, inexpensive option with a rapid turnaround. Several 'multiplex' LFDs (M-LFDs) now exist, testing for multiple pathogens from a single swab sample. We evaluated the real-world performance of M-LFD versus PCR testing in detecting influenza A, B and SARS-CoV-2) in the ED setting.

METHODS: After preliminary evaluation of an M-LFD (SureScreen) with laboratory-grown virus and PCR-negative clinical samples, it was evaluated in a real-world setting at the ED of St Thomas' Hospital (London, …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Med12 Loss-Of-Function Variants As A Cause Of Congenital Diaphragmatic Hernia In Females With Hardikar Syndrome And Nonspecific Intellectual Disability, Eric C Kao, Elizabeth A Mizerik, Carlos A Bacino, Hongzheng Dai, Liesbeth Vossaert, Daryl A Scott

Faculty, Staff and Students Publications

Mediator complex subunit 12 (MED12) is required for the assembly of the kinase module of Mediator, a regulatory complex that controls the formation of the RNA polymerase II-mediated preinitiation complex. MED12-related disorders display unique gender-specific genotype-phenotype associations and include X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants, and X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de novo nonsense/frameshift and nonsense/missense variants, respectively. MED12 was previously identified as a low-penetrance candidate gene for non-isolated congenital diaphragmatic hernia (CDH+). At the time, however, there was …

A Murine Model Of Gestational Diabetes Reveals Masld Risk And Alterations In Markers Of Hepatic Mitochondrial Metabolism, Grace E Shryack, Alexa A Krause, Simone Hernandez Ruano, Laura C Schulz, Kathleen A Pennington, R Scott Rector

Faculty, Staff and Students Publications

Introduction: Gestational Diabetes Mellitus (GDM) impacts roughly 1 in 7 pregnancies and results in metabolic dysfunction-associated steatotic liver disease (MASLD) in 30% of these women. Nonetheless, there exists a dearth of investigation into the relationship between GDM and MASLD. Here, we sought to investigate the potential role of hepatic mitochondrial function in GDM and MASLD.

Methods: One week prior to conception and throughout pregnancy, mice were fed either a low-fat control diet (CD) or a high-fat, high-sucrose (HFHS) diet to induce an established model of GDM. Maternal livers were collected at day 0, 6.5, 13.5 and 17.5 of pregnancy. Hepatic …

Follow-Up Adherence After Teleretinal Screening For Diabetic Retinopathy, Paul D Chamberlain, Rishabh C Date, Kevin L Shen, Giovanni A Campagna, Linda B Piller, Yvonne I Chu, Christina Y Weng

Faculty, Staff and Students Publications

Aim: Determine the follow-up rate for patients referred following an abnormal teleretinal imaging (TRI) screening and examine patient characteristics predictive of follow-up nonadherence.

Materials and methods: A cross-sectional study of patients screened between August 2014 and July 2016 in the Harris Health System (HHS) in Houston, TX. All diabetic patients referred for in-person examination, who had data for all study variables, and who did not have established ophthalmic care in the HHS within the previous 2 years were included. Data collected included TRI findings, clinic location, age, race, gender, hemoglobin A1C (HbA1c), and insulin use. The primary outcome was whether …

Nitrate And Nitrite Bioavailability In Plasma And Saliva: Their Association With Blood Pressure - A Systematic Review And Meta-Analysis, Raul Bescos, Laura Gallardo-Alfaro, Ammar Ashor, Lucia Rizzolo-Brime, Mario Siervo, Patricia Casas-Agustench

School of Health Professions

In this study, we conducted a systematic review and meta-analysis to determine plasma and salivary nitrate (NO ₃ ⁻) and nitrite (NO ₂ ⁻) concentrations under resting and fasting conditions in different type of individuals and their association with blood pressure levels. A total of 77 studies, involving 1918 individuals aged 19–74 years (males = 906; females = 1012), which measured plasma and/or salivary NO ₃ ⁻ and NO ₂ ⁻ using the chemiluminescence technique, were included. Mean plasma NO ₃ ⁻ and NO ₂ ⁻ concentrations were 33.9 μmol/L and 158.3 nmol/L, respectively. Subgroup analyses revealed lower …

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, Zachary M Sellers, Matthew J Giefer, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Z Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Tanja Y Gonska, Amit S Grover, Doug Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Madhura Y Phadke, Wenly Ruan, Sarah Jane Schwarzenberg, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (< 150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.

Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic …

Refinement Of A Published Gene-Physical Activity Interaction Impacting Hdl-Cholesterol: Role Of Sex And Lipoprotein Subfractions, Kenneth E Westerman, Tuomas O Kilpeläinen, Magdalena Sevilla-Gonzalez, Margery A Connelly, Alexis C Wood, Michael Y Tsai, Kent D Taylor, Stephen S Rich, Jerome I Rotter, James D Otvos, Amy R Bentley, Samia Mora, Hugues Aschard, D C Rao, Charles Gu, Daniel I Chasman, Alisa K Manning

Faculty, Staff and Students Publications

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women’s Genome Health Study (WGHS; N=23,294; the strongest cohort-specific signal in the original meta-analysis), the UK …