Digital Commons Network^™

Prevalence Of Sexual Desire And Arousal Difficulties Among Women Veterans: A Retrospective Cohort Design, Alexandra B Caloudas, Amber B Amspoker, Melinda Stanley, Derrecka Boykin, Kelley Arredondo, Annette Walder, Julianna Hogan, Jan A Lindsay

Faculty, Staff and Students Publications

Low sexual desire and arousal are associated with several negative health outcomes, including reduced quality of life, depression, anxiety, and relationship discord. Although women veterans have high rates of risk factors for sexual dysfunctions (e.g., elevated rates of trauma, depression, anxiety), research on their sexual functioning is lacking. Using a retrospective cohort design, we examined the prevalence of documented sexual desire and arousal disorder diagnoses or symptoms, using ICD-10 codes, among 790,726 women veterans receiving care in the Veterans Health Administration. In Fiscal Year 2020, these symptoms and disorders were documented for only 0.19% (n = 1,494) of women veterans …

Gastrointestinal Infections Modulate The Risk For Insulin Autoantibodies As The First-Appearing Autoantibody In The Teddy Study, Maria Lönnrot, Kristian F Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A Mcindoe, Jorma Toppari, Anette-G Ziegler, Joseph F Petrosino, Richard Lloyd, Heikki Hyöty, Teddy Study Group

Faculty, Staff and Students Publications

OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

RESULTS: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at(OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in …

Obesity Dominates Early Effects On Cardiac Structure And Arterial Stiffness In People With Type 2 Diabetes, Layla A Abushamat, Daniel Enge, Takashi Fujiwara, Michal Schäfer, Ethan W Clark, Erin K Englund, Rebecca L Scalzo, Aspen Johnston, Deirdre Rafferty, Irene E Schauer, Mary O Whipple, Kendall Hunter, Amy G Huebschmann, Kristen J Nadeau, Kelly Jarvis, Alex J Barker, Judith G Regensteiner, Jane E B Reusch

Faculty, Staff and Students Publications

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was …

The Impact Of Vaccine-Linked Chemotherapy On Liver Health In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Duc Minh Nguyen, Cristina Poveda, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez, Kathryn Marie Jones

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. …

Pediatric Microsurgery And Free-Tissue Transfer, Heather R Burns, Anna J Skochdopole, Richardo Alfaro Zeledon, William C Pederson

Faculty, Staff and Students Publications

Advancements in microsurgery, along with increased microsurgical experience in pediatric patients, have made free-tissue transfer a reliable modality for pediatric bone and soft tissue reconstruction today. Free-tissue transfer is most commonly used in children for the coverage of large or complex defects resulting from traumatic, oncologic, or congenital etiologies. While flap success and complication rates between pediatric and adult populations are similar, special considerations must be taken into account within the pediatric population. In this article, we will describe common indications, technical nuances, and clinical considerations for the management of the pediatric free-tissue transfer patient.

Highly Invasive Biliary Cancer Presenting As Multiple Extrabiliary Lesions Masquerading As Abscesses, Alexander Lu, Alireza Mojtahedi, Lukman Cheraghvandi, David Wynne, Neda Zarrin-Khameh, Mohammad Ghasemi Rad

Faculty, Staff and Students Publications

Carcinosarcomas of the biliary tract are an extremely rare type of malignancy and may be low on a differential when presenting as multiple metastatic masses. In this case report, we report a case of a female who presented with an aggressive late-stage disease whose initial workup did not indicate a malignant process. Further complicating her care, biopsy samples taken from extra-hepatic masses were culture-positive for Lactobacillus rhamnosu. Given the late stage of the patient’s disease, hospice care was initiated. The patient passed away four months after the initial presentation.

Targeted Inhibition Of Lncrna Malat1 Alters The Tumor Immune Microenvironment In Preclinical Syngeneic Mouse Models Of Triple-Negative Breast Cancer, Oluwatoyosi Adewunmi, Yichao Shen, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Long noncoding RNAs (lncRNA) play an important role in gene regulation in both normal tissues and cancer. Targeting lncRNAs is a promising therapeutic approach that has become feasible through the development of gapmer antisense oligonucleotides (ASO). Metastasis-associated lung adenocarcinoma transcript (Malat1) is an abundant lncRNA whose expression is upregulated in several cancers. Although Malat1 increases the migratory and invasive properties of tumor cells, its role in the tumor microenvironment (TME) is still not well defined. We explored the connection between Malat1 and the tumor immune microenvironment (TIME) using several immune-competent preclinical syngeneic Tp53-null triple-negative breast cancer (TNBC) mouse models that …

Aso Silencing Of A Glycosyltransferase, Poglut1, Improves The Liver Phenotypes In Mouse Models Of Alagille Syndrome, Nima Niknejad, Duncan Fox, Jennifer L Burwinkel, Neda Zarrin-Khameh, Soomin Cho, Armand Soriano, Ashley E Cast, Mario F Lopez, Kari A Huppert, Frank Rigo, Stacey S Huppert, Paymaan Jafar-Nejad, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Paucity of intrahepatic bile ducts (BDs) is caused by various etiologies and often leads to cholestatic liver disease. For example, in patients with Alagille syndrome (ALGS), which is a genetic disease primarily caused by mutations in jagged 1 ( JAG1) , BD paucity often results in severe cholestasis and liver damage. However, no mechanism-based therapy exists to restore the biliary system in ALGS or other diseases associated with BD paucity. Based on previous genetic observations, we investigated whether postnatal knockdown of the glycosyltransferase gene protein O -glucosyltransferase 1 ( Poglut1) can improve the ALGS liver phenotypes in …

Dominant Negative Variants In Ikzf2 Cause Ichad Syndrome, A New Disorder Characterized By Immunodysregulation, Craniofacial Anomalies, Hearing Impairment, Athelia, And Developmental Delay, Arezoo Mohajeri, Maryam Vaseghi-Shanjani, Jill A Rosenfeld, Gui Xiang Yang, Henry Lu, Mehul Sharma, Susan Lin, Areesha Salman, Meriam Waqas, Mahshid Sababi Azamian, Kim C Worley, Kate L Del Bel, Frederick K Kozak, Ronak Rahmanian, Catherine M Biggs, Kyla J Hildebrand, Seema R Lalani, Sarah K Nicholas, Daryl A Scott, Sara Mostafavi, Clara Van Karnebeek, Erika Henkelman, Jessica Halparin, Connie L Yang, Linlea Armstrong, Undiagnosed Diseases Network, Anna Lehman Care 4 Rare Canada Consortium, Stuart E Turvey

Faculty, Staff and Students Publications

Background:

Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognized for its role in the development and function of T lymphocytes, particularly the CD4⁺ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.

Methods:

We performed detailed phenotypic, genomic, and functional investigations on …

Accuracy And Safety Of Non-Image Guided Trigger Finger Injections: A Cadaveric Study, Daniel D Binz, Thomas W Mitchell, Scott A Mitchell

Faculty, Staff and Students Publications

BACKGROUND: Stenosing flexor tenosynovitis is commonly treated by injection of corticosteroids into the flexor tendon sheath. However, there is no consensus in the literature regarding the optimal technique, specifically when not utilizing ultrasound guidance. Here, we present a cadaver study in which 3 common techniques of flexor sheath injection were compared with regard to their accuracy and safety profiles.

METHODS: Fifteen fresh-frozen cadaver hands (60 digits) were evenly divided into 3 groups (20 digits per group). Digits in each group were injected with methylene blue dye using 1 of the 3 techniques (palmar-to-bone, palmar supra-tendinous, and mid-axial). The fingers were …

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

International Union Of Basic And Clinical Pharmacology Cxiii: Nuclear Receptor Superfamily-Update 2023, Thomas P Burris, Ian Mitchelle S De Vera, Isabelle Cote, Colin A Flaveny, Udayanga S Wanninayake, Arindam Chatterjee, John K Walker, Nickolas Steinauer, Jinsong Zhang, Laurel A Coons, Kenneth S Korach, Derek W Cain, Anthony N Hollenberg, Paul Webb, Douglas Forrest, Anton M Jetten, Dean P Edwards, Sandra L Grimm, Sean Hartig, Carol A Lange, Jennifer K Richer, Carol A Sartorius, Marc Tetel, Cyrielle Billon, Bahaa Elgendy, Lamees Hegazy, Kristine Griffett, Nahuel Peinetti, Kerry L Burnstein, Travis S Hughes, Sadichha Sitaula, Keitch R Stayrook, Alexander Culver, Meghan H Murray, Brian N Finck, John A Cidlowski

Faculty, Staff and Students Publications

The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development derived from integrating various approaches, including biophysical techniques, structural studies, and translational investigation. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling. SIGNIFICANCE STATEMENT: Nuclear …

Sarcopenia Is Associated With Osteopenia And Impaired Quality Of Life In Children With Genetic Intrahepatic Cholestatic Liver Disease, Julia M Boster, Nathan P Goodrich, Cathie Spino, Kathleen M Loomes, Estella M Alonso, Binita M Kamath, Ronald J Sokol, Saul Karpen, Alexander Miethke, Benjamin L Shneider, Jean P Molleston, Rohit Kohli, Simon P Horslen, Philip Rosenthal, Pamela L Valentino, Jeffrey H Teckman, Thomas N Hangartner, Shikha S Sundaram

Faculty, Staff and Students Publications

BACKGROUND: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

METHODS: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Relationships between eSMM, liver disease, and transplant-free survival were assessed.

RESULTS: eSMM was …

Camkk2 As An Emerging Treatment Target For Bipolar Disorder, Jacqueline Kaiser, Kevin Nay, Christopher R Horne, Luke M Mcaloon, Oliver K Fuller, Abbey G Muller, Douglas G Whyte, Anthony R Means, Ken Walder, Michael Berk, Anthony J Hannan, James M Murphy, Mark A Febbraio, Andrew L Gundlach, John W Scott

Faculty, Staff and Students Publications

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug …

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators

Faculty, Staff and Students Publications

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

Market Competition And Anemia Management In The United States Following Dialysis Payment Reform, Anshul Bhatnagar, Vishnupriyadevi Parvathareddy, Wolfgang C Winkelmayer, Glenn M Chertow, Kevin F Erickson

Faculty, Staff and Students Publications

BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown.

OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition.

RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.

SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.

MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of …

Protein Advanced Glycation End Products And Their Implications In Pancreatic Cancer, Lakmini Senavirathna, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in …

Geographic Variation In Late-Stage Cervical Cancer Diagnosis, Itunu O Sokale, Aaron P Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G Chido-Amajuoyi, Ann Amuta, Lorraine R Reitzel, Abiodun O Oluyomi

Faculty, Staff and Students Publications

IMPORTANCE: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening.

OBJECTIVE: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at …

Mature B-Cell Lymphomas In Adolescents And Young Adults, Nader Kim El-Mallawany, Lisa Giulino-Roth, John M Burke, Michelle Hermiston, Carl E Allen

Faculty, Staff and Students Publications

Pediatric non-Hodgkin lymphoma includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the US, compared to >60,000 cases of adult NHL annually. Improvements in survival in pediatric and adolescent mature B cell NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes through dose escalation of chemotherapy and, more recently, targeted therapy with rituximab. Pediatric dose-intense strategies carry risks of long-term consequences, but treatment failure is nearly universally fatal. By comparison, adult mature B cell lymphoma is typically less aggressive and treated with less …

Effectiveness Of Icosapent Ethyl On First And Total Cardiovascular Events In Patients With Metabolic Syndrome, But Without Diabetes: Reduce-It Metsyn, Michael Miller, Deepak L Bhatt, Eliot A Brinton, Terry A Jacobson, Philippe Gabriel Steg, Armando Lira Pineda, Steven B Ketchum, Ralph T Doyle, Jean-Claude Tardif, Christie M Ballantyne

Faculty, Staff and Students Publications

Aims: Metabolic syndrome (MetSyn) is associated with high risk of cardiovascular (CV) events, irrespective of statin therapy. In the overall REDUCE-IT study of statin-treated patients, icosapent ethyl (IPE) reduced the risk of the primary composite endpoint (CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization) and the key secondary composite endpoint (CV death, non-fatal myocardial infarction, or non-fatal stroke).

Methods and results: REDUCE-IT was an international, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled LDL cholesterol and elevated triglycerides, to IPE 4 g/day or placebo. The current study evaluated the pre-specified …

Oral Follicle-Stimulating Hormone Receptor Agonist Affects Granulosa Cells Differently Than Recombinant Human Fsh, Joie Z Guner, Diana Monsivais, Henry Yu, Fabio Stossi, Hannah L Johnson, William E Gibbons, Martin M Matzuk, Stephen Palmer

Faculty, Staff and Students Publications

Objective:

To determine whether TOP5300, a novel oral follicle stimulating hormone receptor (FSHR) allosteric agonist, elicits a different cellular response than recombinant human FSH (rh-FSH) in human granulosa cells from in vitro fertilization patients.

Design:

Basic science research with a preclinical allosteric FSHR agonist.

Subjects:

Infertility patients at a single academic fertility clinic were recruited under an IRB-approved protocol. Primary granulosa cell cultures were established for 41 patients, of which 8 had normal ovarian reserve (NOR), 17 were of advanced reproductive age (ARA), 12 had a diagnosis of polycystic ovarian syndrome (PCOS), and 4 had a combination of diagnoses, such …

State-Of-The-Art Document On Optimal Contemporary Management Of Cardiomyopathies, Petar M Seferović, Marija Polovina, Giuseppe Rosano, Biykem Bozkurt, Marco Metra, Stephane Heymans, Wilfried Mullens, Johann Bauersachs, Karen Sliwa, Rudolf A De Boer, Dimitrios Farmakis, Thomas Thum, Iacopo Olivotto, Claudio Rapezzi, Aleš Linhart, Domenico Corrado, Carsten Tschöpe, Ivan Milinković, Antoni Bayes Genis, Gerasimos Filippatos, Andre Keren, Milika Ašanin, Gordana Krljanac, Ružica Maksimović, Hadi Skouri, Tuvia Ben Gal, Brenda Moura, Maurizio Volterrani, Magdy Abdelhamid, Yuri Lopatin, Ovidiu Chioncel, Andrew J S Coats

Faculty, Staff and Students Publications

Cardiomyopathies represent significant contributors to cardiovascular morbidity and mortality. Over the past decades, a progress has occurred in characterization of the genetic background and major pathophysiological mechanisms, which has been incorporated into a more nuanced diagnostic approach and risk stratification. Furthermore, medications targeting core disease processes and/or their downstream adverse effects have been introduced for several cardiomyopathies. Combined with standard care and prevention of sudden cardiac death, these novel and emerging targeted therapies offer a possibility of improving the outcomes in several cardiomyopathies. Therefore, the aim of this document is to summarize practical approaches to the treatment of cardiomyopathies, which …

Health-Related Quality Of Life In A Systematically Assessed Cohort Of Children And Adults With Urea Cycle Disorders, Chaya N Murali, John R Barber, Robert Mccarter, Anqing Zhang, Natalie Gallant, Kara Simpson, Naghmeh Dorrani, Greta N Wilkening, Ron D Hays, Uta Lichter-Konecki, Members Of The Urea Cycle Disorders Consortium, Lindsay C Burrage, Sandesh C S Nagamani

Faculty, Staff and Students Publications

PURPOSE: Individuals with urea cycle disorders (UCDs) may develop recurrent hyperammonemia, episodic encephalopathy, and neurological sequelae which can impact Health-related Quality of Life (HRQoL). To date, there have been no systematic studies of HRQoL in people with UCDs.

METHODS: We reviewed HRQoL and clinical data for 190 children and 203 adults enrolled in a multicenter UCD natural history study. Physical and psychosocial HRQoL in people with UCDs were compared to HRQoL in healthy people and people with phenylketonuria (PKU) and diabetes mellitus. We assessed relationships between HRQoL, UCD diagnosis, and disease severity. Finally, we calculated sample sizes required to detect …

Monitoring The Treatment Of Urea Cycle Disorders Using Phenylbutyrate Metabolite Analyses: Still Many Lessons To Learn, Kevin E Glinton, Charles G Minard, Ning Liu, Qin Sun, Sarah H Elsea, Lindsay C Burrage, Sandesh C S Nagamani

Faculty, Staff and Students Publications

Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium phenylacetate (NaPAA) are important for the management of urea cycle disorders (UCDs). Plasma concentrations of their primary metabolite, phenylacetate (PAA), as well as the ratio of PAA to phenylacetylglutamine (PAGN) are useful for guiding dosing and detecting toxicity. However, the frequency of toxic elevations of metabolites and associated clinical covariates is relatively unknown. A retrospective analysis was conducted on 1255 plasma phenylbutyrate metabolite measurements from 387 individuals. An additional analysis was also conducted on a subset of 68 …

Interplay Between Epigenetic And Genetic Alterations In Inborn Errors Of Immunity, Javier Rodríguez-Ubreva, Celia L Calvillo, Lisa R Forbes Satter, Esteban Ballestar

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interactors. Therefore, we posit that epigenetic alterations and genetic defects do not exclude each other as a disease-causing etiology. In this opinion, encompassing both basic and clinical viewpoints, we focus on selected IEIs with mutations in transcription …

Correlations Between Elastic Modulus And Ultrashort Echo Time (Ute) Adiabatic T1Ρ Relaxation Time (Ute-Adiab-T1Ρ) In Achilles Tendons And Entheses, Saeed Jerban, Amir Masoud Afsahi, Yajun Ma, Dina Moazamian, Sheronda Statum, Alecio F Lombardi, Lena Kakos, Erik Dorthe, Daryll Dlima, Jiang Du, Christine B Chung, Eric Y Chang

Faculty, Staff and Students Publications

Patients with psoriatic arthritis commonly have abnormalities of their entheses, which are the connections between tendons and bone. There are shortcomings with the use of conventional magnetic resonance imaging (MRI) sequences for the evaluation of entheses and tendons, whereas ultrashort echo time (UTE) sequences are superior for the detection of high signals, and can also be used for non-invasive quantitative assessments of these structures. The combination of UTE-MRI with an adiabatic-T1ρ preparation (UTE-Adiab-T1ρ) allows for reliable assessment of entheses and tendons with decreased susceptibility to detrimental magic angle effects. This study aimed to investigate the relationship between quantitative UTE-MRI measures …

An Automated Respiratory Data Pipeline For Waveform Characteristic Analysis, Savannah Lusk, Christopher S Ward, Andersen Chang, Avery Twitchell-Heyne, Shaun Fattig, Genevera Allen, Joanna L Jankowsky, Russell S Ray

Faculty, Staff and Students Publications

Comprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds and defining experimental variables. Breathe Easy was validated against manual selection by …

Feasibility Of A Dietary Intervention To Modify Gut Microbial Metabolism In Patients With Hematopoietic Stem Cell Transplantation, Mary M Riwes, Jonathan L Golob, John Magenau, Mengrou Shan, Gregory Dick, Thomas Braun, Thomas M Schmidt, Attaphol Pawarode, Sarah Anand, Monalisa Ghosh, John Maciejewski, Darren King, Sung Choi, Gregory Yanik, Marcus Geer, Ethan Hillman, Costas A Lyssiotis, Muneesh Tewari, Pavan Reddy

Faculty, Staff and Students Publications

Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day −7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they …