Medical Sciences Commons^™

Disentangling Effects Of The Dr And Dq Isomers Encoded By The Hla Class Ii Haplotype Drb1*15:01/Dqb1*06:02 To Help Establish The True Risk Allele For Fviii Inhibitor Development In Hemophilia A, Vincent P Diego, Bernadette W Luu, Marcio A Almeida, Raja Rajalingam, Marco Hofmann, Jacob A Galan, Eron G Manusov, Jerry S Powell, Long V Dinh, Henry Mead, Huy Huynh, Anne M Verhagen, Juan M Peralta, Paul V Lehmann, Satish Kumar, Eli J Fine, Joanne E Curran, Harald H Goring, Miguel A Escobar, Sarah Williams-Blangero, Eugene Maraskovsky, John Blangero, Tom E Howard

Faculty, Staff and Student Publications

Introduction: Hemophilia A (HA) patients (HAPs) with the human leukocyte antigen (HLA)-class-II (HLAII) haplotype DRB1*15:01/DQB1*06:02, and thus antigen presenting cells which express HLAII β-polypeptide chains that form heterodimers of DR15- and DQ6-serotypes, respectively, have an increased risk of developing factor (F)VIII inhibitors (FEIs)-neutralizing antibodies against the therapeutic-FVIII-proteins (tFVIIIs) infused to prevent/arrest bleeding. As DRB1*15:01 and DQB1*06:02 exist in strong linkage disequilibrium, association analysis cannot determine which is the actual risk allele.

Methods: To establish the true risk allele of this haplotype, we analyzed the tFVIII-derived peptides (tFVIII-dPs) bound to either the DR or DQ molecules that comprise the individual HLAII …

Targeting Ferroptosis For Neuroprotection: Potential Therapeutic Avenues In Neurodegenerative And Neuropsychiatric Diseases, Muhammad S Khan, Qichan Hu, Kendrix Okeibunor, Liang Ma, Jean C Bopassa

Faculty, Staff and Student Publications

Ferroptosis is an iron-dependent programmed cell death that plays an important role in neurodegenerative and neuropsychiatric diseases. In the present study, we have highlighted how different risk factors are involved in the induction of ferroptosis in brain cells. In addition, we also demonstrated how ferroptosis plays an important role in different brain diseases. In our study why we focused and elaborated on the mechanisms of ferroptosis only in brain cells (Neurons, oligodendrocytes, and microglia) because they are particularly vulnerable to such kind of cell death. Additionally, brain cells are more dependent on mitochondrial function, iron regulation, and high levels of …

Mic60/Mitofilin Inhibitor, Miclxin, Induces Rat H9c2 Cardiomyoblast Death By Inhibiting The Removal Of Damaged Mitochondria, Muhammad S Khan, Somayyeh Nasiripour, Michele Oyarzabal, Swati Banerjee, Kumar Sharma, Manzoor A Bhat, Jean C Bopassa

Faculty, Staff and Student Publications

Mitochondrial dysfunction is a hallmark of various pathologic conditions, including ischemia/reperfusion injury, stroke, myocardial infarction, neurodegeneration and metabolic syndrome. As with all biological organelles, the function of mitochondria is tightly linked to their structure. The inner mitochondrial membrane is a highly regulated membrane with a large surface area that hosts the electron transport chain machinery, generates the membrane potential necessary for ATP generation, and forms the signature cristae folds of mitochondria. The mitochondrial inner membrane protein (Mitofilin/Mic60) is part of a large complex that constitutes the mitochondrial inner membrane organizing system, which is critical in maintaining mitochondrial architecture and function. …

Haemodynamic Response Of Normal Aortic Valves To Stress Using Invasive, Non-Invasive, And Computational Techniques, Rob Eerdekens, Vijay Govindarajan, Nils P Johnson, Jesse P A Demandt, Mohamed El Farissi, Fabienne E Vervaat, Daniel T Johnson, Richard L Kirkeeide, Pim A L Tonino

Faculty, Staff and Student Publications

AIMS: The haemodynamic physiology of the aortic valve has attracted renewed attention after the introduction of transcatheter aortic valve implantation (TAVI). Understanding normal valve function, especially under stress conditions, permits identification of early pathology and quantification of the extent to which TAVI restores normalcy. We aimed to describe the haemodynamic behaviour of a normal aortic valve during stress via invasive, non-invasive, and computational techniques.

METHODS AND RESULTS: Our cohort included subjects already undergoing invasive coronary angiography for clinical indications. Haemodynamic measurements were made invasively and non-invasively along with dobutamine infusion. Additionally, patient-specific anatomy from computed tomographic imaging served as input …

Characterizing Fermentable Carbohydrate Foods In The Diets Of Children With Abdominal Pain-Related Disorders Of Gut-Brain Interaction And Healthy Children, Vishnu Narayana, Jocelyn Chang, Ann R Mcmeans, Tasha Murphy, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Restricting dietary fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can alleviate symptoms in children with disorders of gut-brain interaction (DGBI). Due to the restrictions of a low FODMAP diet (LFD), a less restrictive FODMAP Gentle diet (FGD) has been suggested. However, the types and amounts of high FODMAP foods and carbohydrates commonly consumed by children have not been studied. We aimed to identify the high FODMAP foods and proportions of FODMAP carbohydrates consumed by children with DGBI and healthy children (HC) and to determine which usually ingested FODMAPs would be restricted on the FGD.

Methods: Three-day diet records from …

Ethical Considerations For Teaching With Artificial Intelligence: A Scoping Review In Medical Education Settings, Amani Itani, Susie L Gronseth, Salma Musaad, Thuy Nguyen, Yiming Mirabile, Bettina M Beech

Children’s Nutrition Research Center Staff Publications

In the evolving realm of medical education, where artificial intelligence (AI) technologies play an increasingly pivotal role, embedding AI ethics within educational frameworks has become crucial. This scoping review explores the breadth of literature concerning ethical considerations for teaching with AI in medical education settings. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, the team analyzed 82 peer-reviewed English-language articles published between 2018 and October 2023, sourced from PubMed, Embase, and Web of Science. The review presents insights into the geographic distribution of studies, publication trends, article types, common keywords, areas of …

A Hybrid Cloud Data Lake Architecture Supporting The Integration Of Clinical And Genomics Data, Apollo Mcowiti, Heidi Dowst, Fei Zheng, Susan Hilsenbeck, Christopher Amos

Center for Medical Ethics and Health Policy Staff Publications

Objective: Cancer centers must quickly integrate clinical genomics data from different vendors for oncology operations and research. Clinical data warehouse architectures are costly to construct and brittle, and they are not readily amenable to the rapid changes in oncology research. We introduce a cost-effective hybrid cloud Data Lake architecture for storing clinical genomic data from different vendors, aiding both clinical and research workflows.

Methods: We created a Data Lake architecture based on the zone architecture, with four layers: ingestion, storage, transformation, and interaction. The layers are implemented with a hybrid cloud architecture. Rich metadata created from patient and genomic data …

The Demodex Expert Panel On Treatment And Eyelid Health (Depth) Consensus Regarding The Preferred Treatment For Demodex Blepharitis, Eric Donnenfeld, Kelly K Nichols, Brandon D Ayres, Marjan Farid, Preeya K Gupta, Richard Lyndon Lindstrom, Stephen Pflugfelder, Christopher E Starr, Nandini Venkateswaran, Ian Benjamin Gaddie, Paul M Karpecki, Cecelia Koetting, Selina Mcgee, Laura M Periman, Elizabeth Yeu

Faculty, Staff and Students Publications

Purpose: To reach consensus on Demodex blepharitis (DB) treatment approaches using a modified Delphi process involving 15 ocular surface disease experts.

Methods: The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) consisted of 15 well-published ocular surface disease experts. Panelists completed two online surveys, a live consensus meeting, and a follow-up survey. The surveys consisted of scaled and multiple-choice questions related to the clinical and patient-reported outcomes of DB and its treatment. For the scaled questions using a 1 to 9 Likert scale, consensus was defined as weighted mean scores of 1-3 and 7-9, whereas for multiple-choice questions, consensus …

Two-Dimensional Speckle Tracking Of The Ascending Aorta: A Novel Approach To Evaluate Arterial Stiffness In Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography, Anmol Goyal, Anitha Parthiban, David A White, Daniel Forsha, Doaa Aly

Faculty, Staff and Students Publications

Background: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.

Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode …

Initiating Insulin Pumps In Youth With New-Onset Type 1 Diabetes: A Quality Improvement Initiative, Mili Vakharia, Sarah K Lyons, Don Buckingham, Mark Rittenhouse, Siripoom Mckay, Rona Sonabend, Grace Kim

Faculty, Staff and Students Publications

Introduction: Insulin pump therapy is recommended for youth with type 1 diabetes (T1D) as it enhances quality of life and improves glycemic management. We led a quality improvement initiative to increase insulin pump use in youth younger than 18 years of age with recently diagnosed T1D (duration < 1 y) from a baseline of 17% to 27% from January 2021 to December 2023. As a balancing measure, we evaluated the diabetes-related ketoacidosis (DKA) rate in the same cohort as nonpump users.

Methods: We implemented the following plan-do-study-act cycles: (1) development and implementation of pump initiation algorithm, including minimal safe start criteria and education on ketosis management with pump action plan, (2) establishing clinic follow-up within 90 days of pump start, (3) expansion of the pump algorithm at additional clinic locations, (4) early patient/caregiver education …

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 …

Prospective Multicenter Longitudinal Measurement Of Liver Stiffness In School-Age Children With Cholestatic Liver Disease, Benjamin L Shneider, Nathan P Goodrich, Wen Ye, Jean P Molleston, Daniel H Leung, Ronald J Sokol, Laurel Cavallo, Kasper Wang, Pamela L Valentino, Jeffery H Teckman, James E Squires, Shikha S Sundaram, Philip Rosenthal, Rene Romero, Alexander G Miethke, Kathleen M Loomes, Rohit Kohli, Saul J Karpen, Binita M Kamath, M Kyle Jensen, Jorge A Bezerra, Lee M Bass, John C Magee, Children

Faculty, Staff and Students Publications

Background and aims: A multicenter prospective longitudinal study of vibration-controlled transient elastography (VCTE) in school-age children with biliary atresia (BA), alpha-1 antitrypsin deficiency (a1-AT) and Alagille syndrome (ALGS) was undertaken to test the hypothesis that there would be measurable disease progression over 2 years.

Methods: Vibration-controlled transient elastography was performed annually for 2 years in children with BA, a1-AT and ALGS.

Results: Valid liver stiffness measurement (LSM) was determined at baseline/second follow-up in 254/180 (71%), 104/58 (56%) and 100/61 (61%) participants (mean elapsed time 2.27 years) with BA, a1-AT and ALGS, respectively. Modeling did not reveal a relationship between LSM …

Risk Scores For Choledocholithiasis Perform Poorly In Patients With Hemolytic Diseases: A Pedi Database Report, Jennifer Thompson, Wenly Ruan, Douglas S Fishman, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Valerio Balassone, Filippo Torroni, Paola De Angelis, Simona Faraci, Cynthia Tsai, Michael Wilsey, Racha Khalaf, Petar Mamula, Quin Liu, Yuhua Zheng, Bradley A Barth, David Michael Troendle

Faculty, Staff and Students Publications

Patients with hemolytic diseases are at increased risk for gallstone-related complications. Modified scoring systems have been developed to assess which pediatric patients would benefit from endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis. This study aimed to evaluate the ability of the available criteria to determine which pediatric patients with hemolytic diseases are likely to benefit from ERCP. A secondary analysis was performed using the Pediatric ERCP Database Initiative database, which contains prospectively collected data from 1,124 ERCPs at tertiary-care institutions. We compared patients with a hemolytic disease to those without. Data was analyzed by two-tailed Fisher’s exact test and paired …

Comment On “Effectiveness And Safety Of Oral Vancomycin For The Treatment Of Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis: A Systematic Review And Pooled Analysis”, Richard Kellermayer, Peter Lewindon, Cynthia Buness, James Tabibian, Kevin Johnson, Shamita Shah, Parambir Dulai, Ahmad H Ali, Ayesha Shah, Gerald Holtmann, Harland S Winter

Faculty, Staff and Students Publications

No abstract provided.

Detection Of Viral Rna And Dna And Immune Response Following Administration Of Live Attenuated Measles And Varicella Vaccines In Children With Chronic Liver Disease, Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman

Faculty, Staff and Students Publications

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all …

Eradication Rates Of Empiric Helicobacter Pylori Treatment Regimens By Race/Ethnicity In A Predominantly Immigrant Us Population, Min J Kim, Isiah Gonzalez, Nia M Choi, 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 …

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 …

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 …

Tb And Diabetes In Eswatini: Addressing Suboptimal Treatment Outcomes Through Integrated Services, Yael Hirsch-Moverman, Dana Bezuidenhout, Sakthi Senthilvelan, Lobsang Palmo, Debrah Vambe, Ntombifuthi Ginindza, Nonhlanhla Dlamini, Andrea A Howard, Joanne E Mantell

Faculty, Staff and Students Publications

Tuberculosis (TB) remains a significant public health challenge in Eswatini, a country with the highest global HIV prevalence. Diabetes mellitus (DM) is increasingly common among people newly diagnosed with TB, contributing to suboptimal TB treatment outcomes, including relapse and death. The DETECT study employed a multi-method approach to assess the prevalence and DM impact on TB treatment outcomes among adults with TB in 10 Ministry of Health facilities in Eswatini, and explore barriers and facilitators to integrating TB/DM services. DM screening was conducted using laboratory-based glycated hemoglobin (A1c) testing, with DM defined as A1c ≥ 6.5% and preDM as A1c …

Screening And Targeted Sequencing Of Stool For Microbiologic Confirmation And Drug Resistance Determination In Paucibacillary Tuberculosis, Tara E Ness, Mangaliso Ziyane, Nontobeko Maphalala, Abigail Seeger, Anca Vasiliu, Wethusonke Khumalo, Mdigo Thunzini, Sindisiwe Dlamini, Gugu Maphalala, Clement Gascua, Christoph Lange, Samantha Meyer, Bryce Inman, Viola Dreyer, Christian Utpatel, Tanja Niemann, Andrew Dinardo, Alexander Kay, Stefan Niemann, Anna Mandalakas

Faculty, Staff and Students Publications

In 2023, an estimated 10.8 million people developed tuberculosis, and 1.25 million people died from this disease, including 161,000 deaths in people with HIV (PWH) in whom tuberculosis remains the leading cause of death. Detecting Mycobacterium tuberculosis drug resistance remains a challenge among patients with paucibacillary tuberculosis; since there is such low bacterial load in their sputum it's unable to be detected via microscopy, there is also not enough bacteria for other sputum-based tests which could provide resistance testing. At an outpatient clinic in Eswatini from 2020-2023, stool and sputum samples were provided by a subset of children, adolescents, and …

The Catastrophic Cost Of Tb Care: Understanding Costs Incurred By Individuals Undergoing Tb Care In Low-, Middle-, And High-Income Settings – A Systematic Review, Olivia Alise D'Silva, Samantha Lancione, Oviya Ananthakrishnan, Angelina Addae, Suvesh Shrestha, Hannah Alsdurf, Kednapa Thavorn, Nompumelelo Mzizi, Anca Vasilu, Alexander Kay, Anna Maria Mandalakas, Alice Anne Zwerling

Faculty, Staff and Students Publications

Eliminating the burden of catastrophic costs experienced by individuals undergoing tuberculosis (TB) treatment is one of the World Health Organization (WHO) End TB Strategy targets. To help inform decisions on TB patient burden and cost-effective TB care, we conducted a systematic review to summarize current evidence around the burden of catastrophic costs incurred by individuals undergoing TB treatment and identified the main drivers of costs to aid in developing mitigation strategies. A literature search was performed in August 2024 using Embase, Web of Science, Scopus and Medline targeting studies using WHO, or WHO adapted patient costing questionnaires to measure direct …

Healthcare Providers’ Knowledge, Attitudes, And Perceptions From Using Targeted Sequencing To Diagnose And Manage Drug-Resistant Tuberculosis (Dr-Tb) In Eswatini, Maia Madison, Debrah Vambe, Sein Sein Thi, Mangaliso Ziyane, Nosisa Shiba, Babongile Blisset Nkala, Tara Ness, Agostinho Viana Lima, Sindisiwe Dlamini, Siphiwe Ngwenya, Anna Mandalakas, Alexander Kay

Faculty, Staff and Students Publications

Challenges in diagnosing drug-resistant tuberculosis (DR-TB) contribute to a diagnostic gap. Design-locked Targeted Sequencing (TS) assays have the potential to improve DR-TB diagnosis and management. TS assays are now being introduced into low-income, high TB burden settings. Eswatini is among the first high burden countries to have implemented TS for patient care. To evaluate the impact of the current program and optimize future implementation, we evaluated healthcare provider knowledge, attitudes, and perceptions (KAP) of TS and its implementation. We conducted semi-structured interviews with healthcare providers. Interviews were continued until data saturation was reached and analyzed by directed thematic analysis. The …

Hidden Markov Model For Acoustic Pesticide Exposure Detection And Hive Identification In Stingless Bees, Alex Otesbelgue, Amara Jean Orth, Chandler David Fong, Carol Anne Fassbinder-Orth, Betina Blochtein, Maria João Ramos Pereira

Faculty, Staff and Students Publications

Pollinator populations are declining globally at an unprecedented rate, driven by factors such as pathogens, habitat loss, climate change, and the widespread application of pesticides. Although colony losses remain difficult to prevent, precision beekeeping has introduced non-invasive strategies for monitoring hive conditions. Acoustic data, combined with machine learning techniques, has proven effective in detecting stressors and specific events in honeybee colonies; however, such methodologies remain underexplored for stingless bees, a group of native pantropical pollinators. Meliponiculture, the practice of keeping stingless bees, is an expanding field that offers significant economic and conservation benefits. Stingless bees are particularly susceptible to pesticide …

Occult Abdominal Trauma Screening In The Evaluation Of Suspected Child Physical Abuse, Tagrid M Ruiz-Maldonado, Joanne N Wood, Antoinette L Laskey, Christopher S Greeley, Angela Bachim, Daniel M Lindberg, James Anderst, John Melville, Carmen Coombs, Nancy S Harper, Lori Frasier, Farah W Brink, Caitlin E Crumm, Kristine A Campbell

Faculty, Staff and Students Publications

Background and objectives: Occult abdominal trauma (OAT) screening with transaminases, followed by abdominal computed tomography (CT) for transaminase values greater than 80 IU/L, has been recommended in cases of suspected physical abuse. This study aimed to evaluate case characteristics associated with OAT evaluation and determine OAT prevalence in these children.

Methods: Injured children aged younger than 60 months undergoing Child Abuse Pediatrics (CAP) consultation for suspected physical abuse from February 2021 to May 2023 were identified in CAPNET, a multicenter research network. Children with symptoms or signs of intra-abdominal injury were excluded. We identified case characteristics associated with transaminase screening …

An Innovative Approach To Assessing The Psychosocial Impacts On Liver Transplant Recipients: The Prediction-By-Correspondence Analysis, Se-Kang Kim, Rachel A Annunziato

Faculty, Staff and Students Publications

Background: Innovative analytic techniques are applied to the psychological functioning of liver transplant (LT) recipients to comprehend its effect on post-transplant survival, hypothesizing that adherence will be predicted by psychosocial functioning.

Methods: The psychosocial functioning of 248 LT recipients (88 females) aged 19 to 74 is assessed using the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). In addition, the Medication Level Variability Index (MLVI) and biopsy-proven rejection are utilized to evaluate successful adherence. The Z-scores of the SIPAT scores are used to transform them into an ordinal variable with excellent, good, minimally acceptable, and poor categories. We employ a modified …

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 …

Clinical Variation In Lowe Syndrome: What And How?, Eileen D Brewer

Faculty, Staff and Students Publications

Lowe syndrome is an X-linked disorder caused by mutations of the OCRL gene which encodes the enzyme inositol polyphosphate-5-phosphatase OCRL (Ocrl1) and is expressed in almost all body cells. Clinical characteristics involve kidney, brain, eye, muscle, bone, teeth, testes, skin and thrombocytes. Clinical phenotypes are heterogenous among families and even among affected boys in the same family. All have kidney disease varying from severe manifestations of Fanconi syndrome to only low molecular weight proteinuria, hypercalciuria and little kidney disease in the first decade of life. All develop chronic kidney disease (CKD) that typically progresses slowly and reaches stages 4–5 after …

Clues To Transcription/Replication Collision-Induced Dna Damage: It Was Rnap, In The Chromosome, With The Fork, Matthew B Cooke, Christophe Herman, Priya Sivaramakrishnan

Faculty, Staff and Students Publications

DNA replication and RNA transcription processes compete for the same DNA template and, thus, frequently collide. These transcription-replication collisions are thought to lead to genomic instability, which places a selective pressure on organisms to avoid them. Here, we review the predisposing causes, molecular mechanisms, and downstream consequences of transcription-replication collisions (TRCs) with a strong emphasis on prokaryotic model systems, before contrasting prokaryotic findings with cases in eukaryotic systems. Current research points to genomic structure as the primary determinant of steady-state TRC levels and RNA polymerase regulation as the primary inducer of excess TRCs. We review the proposed mechanisms of TRC-induced …

Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low

Faculty, Staff and Students Publications

Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FRβ). Because FRβ does not bind folate until the monocyte/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FRβ might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FRβ knockout mice. We observe that FRβ knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) …