Digital Commons Network^™

Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, Kyle S Liu, Rollin George, Caleb Shin, Jia Q Xiong, Taher Jamali, Yan Liu, Priya Roy, Sonia Singh, Samuel Ma, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

METHODS: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or …

Effects Of Dialysate Potassium Concentration Of 30 Mmol/Leffects Of Dialysate Potassium Concentration Of 30 Mmol/L With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac Arrhythmias In Hemodialysis Patients With Hyperkalemia Arrhythmias In Hemodialysis Patients With Hyperkalemia, David M Charytan, Wolfgang C Winkelmayer, Christopher B Granger, John P Middleton, Charles A Herzog, Glenn M Chertow, James M Eudicone, Jeremy D Whitson, James A Tumlin

Faculty, Staff and Students Publications

The optimal approach towards managing serum potassium (sK+) and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis sK+ 5.1-6.5 mmol/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 mmol/l potassium/1.25 mmol/l calcium dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 mmol/l potassium/1.25 mmol/l calcium dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mmol/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of at least …

Commentary: Impact Of Resistance Training Intensity On Body Composition And Nutritional Intake Among College Women With Overweight And Obesity: A Cluster Randomized Controlled Trial, Joshua L Keller, Sarah E Deemer, Gian Luca Di Tanna, Sherri L Pals, Kevin R Fontaine, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

The Pointer Imaging Baseline Cohort: Associations Between Multimodal Neuroimaging Biomarkers, Cardiovascular Health, And Cognition, Theresa M Harrison, Tyler Ward, Jacinda Taggett, Pauline Maillard, Samuel N Lockhart, Youngkyoo Jung, Laura C Lovato, Robert Koeppe, William J Jagust, Danielle Harvey, Joseph C Masdeu, Hwamee Oh, Darren R Gitelman, Neelum T Aggarwal, Mark A Espeland, Maryjo L Cleveland, Rachel Whitmer, Sarah Tomaszewski Farias, Stephen Salloway, Valory Pavlik, Melissa Yu, Christine Tangney, Heather Snyder, Maria Carrillo, Laura D Baker, Prashanthi Vemuri, Charles Decarli, Susan M Landau

Staff and Researcher Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Methods: Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta-amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk.

Results: A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ-, Aβ+ (29%) participants were older, …

The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Treatment Fidelity And Outcome In Cbt For Youth With Autism: The Meya Fidelity Scale, Bryce D Mcleod, Jeffrey J Wood, Jennifer Cecilione Herbst, Danielle Dunn, Philip C Kendall, Eric A Storch, An Chuen Cho, Kashia A Rosenau

Faculty, Staff and Students Publications

Objective: Assessing treatment fidelity in effectiveness research is critical to interpreting study findings. This paper details the development and initial psychometric evaluation of the Modular Evidence-Based Practices for Youth with Autism Fidelity Scale (MEYA-FS) designed to support the assessment of cognitive-behavioral treatments for youth with autism in effectiveness research.

Method: Recorded treatment sessions (N = 338) were randomly selected from 77 youth (M age = 9.65 years, SD = 1.87; 50.67% White; 85.33% male) who received the Schema, Emotion, and Behavior-Focused Therapy for Children (SEBASTIEN) (n = 51) or Coping Cat (n = 24) program.

Results: …

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 …

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 …

Critiques Of The Cass Review: Fact-Checking The Peer-Reviewed And Grey Literature, Kathleen Mcdeavitt, J Cohn, Stephen B Levine

Faculty, Staff and Students Publications

The Cass Review's final report, published in April 2024, made recommendations to the UK's National Health Service regarding structuring of services for minors with gender-related distress. It recommended cautious use of hormonal interventions in this population and use of research protocols. Some clinician-researchers disagree with the Cass Review's recommendations and have written critiques. A critique of the Cass Review posted on Yale Law School's website in July 2024 has received extensive media coverage. Its references identified three other critiques. In these papers, there were multiple claims that were incorrect or that lacked essential clarification/contextualization. These claims involved (1) the Cass …

Incorporating Individually Defined Brain Health Priorities In Clinical Trial Outcomes: The Electronic Person-Specific Outcome Measure Approach In The United States, Stina Saunders, Ali Jannati, Shane Sheehan, Claudio Toro-Serey, Sean Tobyne, Killian Mcmanus, David Bates, John Showalter, Álvaro Pascual-Leone

Faculty, Staff and Students Publications

Introduction: While a limited number of disease-modifying treatments for Alzheimer's disease (AD) have been approved in the United States, there is caution in adopting these treatments in clinical use. The electronic Person-Specific Outcome Measure (ePSOM) tool was recently developed to establish whether, besides modifying underlying AD pathology, new treatments exerted sufficient beneficial effects in areas that matter the most to an individual.

Methods: We conducted a study to understand how findings from the ePSOM UK study applied in the United States. The ePSOM US survey (May 2023 to January 2024) collected primarily free-text responses in personally defined brain health priorities, …

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 …

A Reflection-Spectroscopy Measured Skin Carotenoid Score Strongly Correlates With Plasma Concentrations Of All Major Dietary Carotenoid Species Except For Lycopene, Qiang Wu, Cheryl Webb Cherry, Stephanie Jilcott Pitts, Melissa N Laska, Neal Craft, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoids can be measured non-invasively using spectroscopy methods to provide a biomarker of total dietary carotenoid and carotenoid-rich fruit and vegetable intake. However, the degree to which skin carotenoid biomarkers reflect intakes of specific carotenoids must be determined for specific devices. Previously, findings were mixed regarding the correlation between reflection spectroscopy (RS)-assessed skin carotenoids and individual plasma carotenoid concentrations. The current study expands on prior analyses to examine the cross-sectional associations between adult RS-assessed skin carotenoids and individual carotenoid species intakes and plasma concentrations, controlling for potential covariates. We hypothesized that RS-assessed skin carotenoid scores would strongly correlate with …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Targeted Analysis Of Dyslexia-Associated Regions On Chromosomes 6, 12 And 15 In Large Multigenerational Cohorts, Nicola H Chapman, Patrick A Navas, Michael O Dorschner, Michele Mehaffey, Karen G Wigg, Kaitlyn M Price, Oxana Y Naumova, Elizabeth N Kerr, Sharon L Guger, Maureen W Lovett, Elena L Grigorenko, Virginia Berninger, Cathy L Barr, Ellen M Wijsman, Wendy H Raskind

Faculty, Staff and Students Publications

Dyslexia is a common learning impairment with a genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date have investigated only limited genomic variation within each locus with no confirmed pathogenic variants identified. Our study is the first to comprehensively sequence both coding and cis-acting regulatory regions of such genes in a large study sample. In a collection of >2000 participants in families from three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate risk genes (DNAAF4, CYP19A1, DCDC2, …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Design And Rationale Of Myoflame-19 Randomised Controlled Trial: Myocardial Protection To Reduce Post-Covid Inflammatory Heart Disease Using Cardiovascular Magnetic Resonance Endpoints, Valentina O Puntmann, Dietrich Beitzke, Andreas Kammerlander, Inga Voges, Dominik D Gabbert, Marcus Doerr, Bishwas Chamling, Biykem Bozkurt, Juan Carlos Kaski, Erica Spatz, Eva Herrmann, Gernot Rohde, Philipp Deleuw, Lenka Taylor, Christine Windemuth-Kieselbach, Cornelia Harz, Marta Santiuste, Laura Schoeckel, Juliana Hirayama, Peter C Taylor, Colin Berry, Eike Nagel

Faculty, Staff and Students Publications

Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing.

Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural …

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 …

Assessing The Cardioprotective Effects Of Exercise In Apoe Mouse Models Using Deep Learning And Photon-Counting Micro-Ct, Alex J Allphin, Rohan Nadkarni, Zay Y Han, Darin P Clark, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: The allelic variations of the apolipoprotein E (APOE) gene play a critical role in regulating lipid metabolism and significantly impact cardiovascular disease risk (CVD). This study aimed to evaluate the impact of exercise on cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT) and deep learning-based segmentation.

Methods: A total of 140 mice were grouped based on APOE genotype (APOE2, APOE3, APOE4), sex, and exercise regimen. All mice were maintained on a controlled diet to isolate the effects of exercise. Low dose cardiac photon counting micro-CT imaging with intrinsic gating was performed …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Microbiota Dynamics During Ascaris Suum Larval Migration: Implications For Host Microbial Communities In A Murine Model, Sergio Castañeda, Cristina Poveda, Charlie Suarez-Reyes, Yifan Wu, Noah Haugen, Luz H Patiño, Jill E Weatherhead, Juan David Ramírez

Faculty, Staff and Students Publications

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a …

"How Can I Get Out Of This?": A Qualitative Study Of The Phenomenology And Functional Impact Of Misophonia In Youth And Families, Andrew Giles Guzick, Catherine Elizabeth Rast, Brenna Burns Maddox, Servando Rodriguez Barajas, Jane Clinger, Joseph Mcguire, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Misophonia is an increasingly recognized disorder characterized by negative emotional and sensory reactions to specific noises. Although misophonia most often begins in childhood, there has been minimal research on its clinical presentation in youth. This qualitative study explored cognitive behavioral processes that are involved in misophonia and its associated functional impairment in young people and their families.

Methods: Focused interviews were conducted with 20 youth with misophonia (ages 10-17) and their parents. Thematic analyses of these interviews using a cognitive behavioral theoretical framework were conducted.

Results: A number of themes were identified, which included internalizing and externalizing cognitive behavioral …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Emily R Waskow, Lisa T Emrick, Jill A Rosenfeld, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott

Faculty, Staff and Students Publications

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.

Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …

Comparing Guillain-Barré Syndrome Outcomes Between Rural And Urban Hospitals In The United States: A Retrospective Cohort Study, Anudeep Surendranath, Rahul Damani, Anushareddy Muddasani, Anupam Kumar Gupta

Faculty, Staff and Students Publications

Background and purpose: Rural-urban disparities in neurological care have been well documented, but limited data exist regarding Guillain-Barré Syndrome (GBS). This study examines differences in patient demographics, hospital characteristics, and outcomes among GBS admissions to rural versus urban hospitals in the United States.

Methods: Using the 2021 National Inpatient Sample, we conducted a retrospective cohort study of adult hospitalizations with a principal diagnosis of GBS. Hospitals were classified as rural or urban based on U.S. census designations. Multivariate logistic and linear regression models were used to assess associations between hospital location and outcomes, adjusting for demographic, clinical, and hospital-level factors. …