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B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi Jan 2025

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …


Med12 Loss-Of-Function Variants As A Cause Of Congenital Diaphragmatic Hernia In Females With Hardikar Syndrome And Nonspecific Intellectual Disability, Hongzheng Dai, Liesbeth Vossaert, Daryl A Scott Jan 2025

Med12 Loss-Of-Function Variants As A Cause Of Congenital Diaphragmatic Hernia In Females With Hardikar Syndrome And Nonspecific Intellectual Disability, 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 Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu Jan 2025

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …


Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Joseph Jankovic, Mariam Hull Jan 2025

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …


Diagnosis And Management Of Cardiometabolic Disease After Spinal Cord Injury: Identifying Gaps In Physician Training And Practices, Ryan Solinsky Jan 2025

Diagnosis And Management Of Cardiometabolic Disease After Spinal Cord Injury: Identifying Gaps In Physician Training And Practices, Ryan Solinsky

Faculty, Staff and Students Publications

CONTEXT: Cardiometabolic disease (CMD) frequently occurs in individuals with spinal cord injury (SCI), with growing awareness surrounding the expansive scope of this problem. As CMD has significant morbidity and mortality, early guidelines-based screening and management have been established. However, the extent to which these guidelines have been adopted are unclear.

OBJECTIVE: Describe physicians' screening and management pattern for CMD in patients with SCI, as compared to SCI-specific CMD screening guidelines, and elucidate variables linked to screening and management patterns.

METHODS: SCI medicine-boarded physicians were surveyed on screening timing for CMD following acute SCI, along with their practice pattern and comfort …


Long-Term Mortality Following Sars-Cov-2 Infection In Rural Versus Urban Dwellers With Autoimmune Or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From The National Covid Cohort Collaborative, Maria I Danila, Elizabeth Reisher, Rena C Patel, Jasvinder A Singh Jan 2025

Long-Term Mortality Following Sars-Cov-2 Infection In Rural Versus Urban Dwellers With Autoimmune Or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From The National Covid Cohort Collaborative, Maria I Danila, Elizabeth Reisher, Rena C Patel, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort.

Methods: This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and …


Follow-Up Adherence After Teleretinal Screening For Diabetic Retinopathy, Giovanni A Campagna, Linda B Piller, Yvonne I Chu, Christina Y Weng Jan 2025

Follow-Up Adherence After Teleretinal Screening For Diabetic Retinopathy, 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 …


Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt Jan 2025

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …


Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat Jan 2025

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, 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 …


Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat Jan 2025

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, 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 …


Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Benjamin A Clayton, George G Rodney Jan 2025

Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Benjamin A Clayton, George G Rodney

Faculty, Staff and Students Publications

Aim: Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.

Methods: Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and …


Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Vlad C Sandulache, David J Hernandez Jan 2025

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …


Plasma Protein-Based And Polygenic Risk Scores Serve Complementary Roles In Predicting Inflammatory Bowel Disease, Manu Shivakumar, Allison R Greenplate, Sokratis A Apostolidis, Seunggeun Lee, Yonghyun Nam, Dokyoon Kim Jan 2025

Plasma Protein-Based And Polygenic Risk Scores Serve Complementary Roles In Predicting Inflammatory Bowel Disease, Manu Shivakumar, Allison R Greenplate, Sokratis A Apostolidis, Seunggeun Lee, Yonghyun Nam, Dokyoon Kim

Faculty, Staff and Students Publications

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), has a significant genetic component and is increasingly prevalent due to environmental factors. Current polygenic risk scores (PRS) have limited predictive power and cannot inform time of symptom onset. Circulating proteomics profiling offers a novel, non-invasive approach for understanding the inflammatory state of complex diseases, enabling the creation of proteomic risk scores (ProRS). This study utilizes data from 51,772 individuals in the UK Biobank to evaluate the unique and combined contributions of PRS and ProRS to IBD risk prediction. We developed ProRS models for CD and UC, assessed …


Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, Jia Q Xiong, Taher Jamali, Yan Liu, Priya Roy, Sonia Singh, Samuel Ma, Hashem B El-Serag, Mimi C Tan Jan 2025

Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, 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 …


Eradication Rates Of Empiric Helicobacter Pylori Treatment Regimens By Race/Ethnicity In A Predominantly Immigrant Us Population, David Y Graham, Hashem B El-Serag, Mimi C Tan Jan 2025

Eradication Rates Of Empiric Helicobacter Pylori Treatment Regimens By Race/Ethnicity In A Predominantly Immigrant Us Population, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background: Helicobacter pylori infections are mostly treated empirically (without antibiotic susceptibility testing). Determining eradication rates of different treatment regimens can inform antibiotic resistance. Our aim was to examine eradication rates of empiric H. pylori treatments based on treatment regimen, race/ethnicity and previous treatment status in a multiethnic U.S.

Materials and methods: This was a retrospective cross-sectional study of patients with a positive H. pylori test from 7/2021 to 4/2022 at Harris Health (Houston, Texas) who had received treatment and eradication testing within 1 year. We compared eradication rates based on treatment regimen, race/ethnicity, and prior treatment and examined other possible …


Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer Jan 2025

Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Introduction: Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.

Methods: Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH …


Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis Jan 2025

Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis

Faculty, Staff and Students Publications

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.

Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.

Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E …


Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, 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 Jan 2025

Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, 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 …


Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott Jan 2025

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, 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 …


Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat Jan 2025

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, 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 …


Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown Jan 2025

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …


Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal Jan 2025

Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Objective: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation.

Design: Randomized, double-blind, placebo-controlled trial (LITROS).

Methods: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone < 10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism.

Results: Among the …


Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, 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 Jan 2025

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, 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 …


Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore Jan 2025

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, 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 …


Hazardous Work Exposures And Working Conditions And The Risk Of Serious Injury Among Latino Day Laborers In Houston, Texas (2014–2021), Vahed Maroufy Jan 2025

Hazardous Work Exposures And Working Conditions And The Risk Of Serious Injury Among Latino Day Laborers In Houston, Texas (2014–2021), Vahed Maroufy

Faculty, Staff and Student Publications

Introduction: Latino day laborers (LDLs) are frequently exposed to workplace hazards that increase their risk of an injury. The purpose of this study was to assess the relative influence of worker and workplace characteristics on serious injuries reported by LDLs at four different time points. We examined the influence of demographic characteristics, hazardous chemical exposures and working conditions using data from four cross-sectional surveys conducted between 2014 and 2021.

Methods: A total of 740 LDL were randomly recruited from public job hiring locations (known as "corners") in Houston Texas to participate in surveys conducted as part of injury risk reduction …


A Directed Content Analysis For Greatest Problems Among People With And Without Traumatic Brain Injury, Brittany Wright, Alexa S Gonzalez, Luis Leon Novelo, Xiangyi Liu, Shannon B Juengst Jan 2025

A Directed Content Analysis For Greatest Problems Among People With And Without Traumatic Brain Injury, Brittany Wright, Alexa S Gonzalez, Luis Leon Novelo, Xiangyi Liu, Shannon B Juengst

Faculty, Staff and Student Publications

Objective: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared with individuals with a history of other neurologic conditions, mental health conditions, and no history of neurologic or mental health conditions.

Design: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4.

Setting: Community.

Participants: A total of 2861 community-dwelling adults (n=274 with TBI; n=289 with other neurologic conditions besides TBI; n=454 with mental health conditions but no neurologic conditions; and n=1844 controls).

Interventions: Not applicable.

Main outcome …


Navigating The Nexus Of Food Insecurity, Anxiety, And Depression In The Face Of Climate Change: A Longitudinal Study In Rural Kenya, Shreela Sharma, Agnes Maigallo Jan 2025

Navigating The Nexus Of Food Insecurity, Anxiety, And Depression In The Face Of Climate Change: A Longitudinal Study In Rural Kenya, Shreela Sharma, Agnes Maigallo

Faculty, Staff and Student Publications

Objective: This study aims to address critical gaps in understanding the bidirectional relationships between food insecurity, anxiety, and depression in Meru County, Kenya. By employing a cross-lagged panel analysis, we seek to clarify these temporal dynamics, contributing to the design of targeted interventions that integrate food security and mental health in the context of climate change.

Methods: A cross-lagged panel analysis was conducted using data from 362 adult participants in a community-based empowerment program (2023) in Meru County, Kenya. Participants completed self-report measures of food insecurity, anxiety, and depression at two time points, 11 weeks apart.

Results: Food insecurity (T1) …


Optimizing Community-Based Hepatitis B And C Care For Engaging Housing-Insecure Individuals, Jack Tsai Jan 2025

Optimizing Community-Based Hepatitis B And C Care For Engaging Housing-Insecure Individuals, Jack Tsai

Faculty, Staff and Student Publications

Introduction

Hepatitis B and C (HBV/HCV) are bloodborne infections, with individuals who have histories of substance use and homelessness bearing a disproportionate risk. Long-standing difficulties in engaging these populations have made testing and treatment challenging. This retrospective observational study describes a community-based approach to HBV/HCV prevention and treatment, comparing the effectiveness of different engagement site types in reaching and engaging this high-need population.

Methods

GRASSROOTS HEALTH was launched in 2018 to improve HBV/HCV care by providing on-site testing, HBV vaccination, treatment navigation, and adherence support across various housing and drop-in centers. Outcomes were tracked through REDCap and analyzed by engagement …


Perspectives On Smoking Cessation In The Oncology Environment: Insights From Brazilian Patients And Healthcare Providers, Raiany Carvalho, Irene Tami-Maury Jan 2025

Perspectives On Smoking Cessation In The Oncology Environment: Insights From Brazilian Patients And Healthcare Providers, Raiany Carvalho, Irene Tami-Maury

Faculty, Staff and Student Publications

Objective: The aim of this study was to identify barriers and facilitators to smoking cessation among Brazilian cancer patients, considering the perspectives of both patients and healthcare professionals at a leading oncology center in the country.

Methods: A cross-sectional study was conducted, collecting smoking-related data from two groups: cancer patients and healthcare professionals at the Barretos Cancer Hospital (BCH) between 2019 and 2021. The questionnaire for healthcare professionals was adapted from the 2012 International Association for the Study of Lung Cancer and the Global Adult Tobacco Survey. For the cancer patient group, sociodemographic and clinical data were collected, along with …


Community-Involved Economic Evaluation And Development Of A Cost-Effectiveness Calculator For Two Peer-Driven Substance Use Interventions, J Michael Wilkerson, H Shelton Brown Jan 2025

Community-Involved Economic Evaluation And Development Of A Cost-Effectiveness Calculator For Two Peer-Driven Substance Use Interventions, J Michael Wilkerson, H Shelton Brown

Faculty, Staff and Student Publications

Introduction: While peer-driven substance use interventions have proliferated across the U.S., economic evaluations of these interventions have lagged behind. A key characteristic of these interventions is the centrality of the "nothing about us without us" ethos, which should extend into economic evaluation research. To that end, this study sought to take a community-based participatory research (CBPR) approach to conducting a cost-effectiveness analysis (CEA) of peer recovery support services (PRSS) and turning that CEA and a CEA of bystander naloxone distribution (BND) into components of a free, web-based calculator for use by recovery community centers (RCCs).

Methods: We engaged staff and …