Diseases Commons^™

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Elevated Level Of Extracellular Vimentin Is Associated With An Increased Fibrin Formation Potential In Sepsis: Ex Vivo Swine Study, Marina Martinez-Vargas, Arun Saini, Subhashree Pradhan, Luis Gardea, Barbara Stoll, Inka C Didelija, K Vinod Vijayan, Trung C Nguyen, Miguel A Cruz

Faculty, Staff and Students Publications

BACKGROUND: Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.

RESULTS: We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma …

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …

Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan

Faculty, Staff and Student Publications

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris

Faculty, Staff and Students Publications

AIMS: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

METHODS AND RESULTS: We included patientsMFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman …

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Experiences Of Parent Coaches In An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Carrie Tully, Manuela Sinisterra, Wendy Levy, Christine H Wang, John Barber, Hailey Inverso, Marisa E Hilliard, Maureen Monaghan, Randi Streisand

Faculty, Staff and Students Publications

Objectives: This paper explores parent coaching experiences supporting parents of young children newly diagnosed with type 1 diabetes in a clinical trial.

Methods: In a trial for 157 parents, those in the intervention arm (n = 116) were paired with a parent coach (n = 37; Mage = 37.9 years, SD = 3.9; 94.6% mothers, 81.1% White non-Hispanic). Parent coaches provided diabetes-specific social support. Parent coaches completed monthly surveys and satisfaction/feasibility surveys, with a subset (n = 7) undergoing qualitative interviews at the end of this study.

Results: There were 2262 contacts between participants and their parent coaches, averaging …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials.

Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV.

Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different …

Right Ventricle-Pulmonary Artery Conduit Replacement Resolves Anomalous Single Coronary Stenosis In Repaired Tetralogy Of Fallot, Karl Kristian Lundin, Edward Hickey, Prakash Masand, Vivian Dimas, Katherine Bohard Salciccioli

Faculty, Staff and Students Publications

A 41-year-old man with repaired tetralogy of Fallot and a single coronary artery (CA) arising anteriorly presented with dyspnea in the setting of moderate right ventricle-pulmonary artery conduit (RV-PAC) stenosis and moderate-to-severe extrinsic left main CA compression between the aorta and RV-PAC. His CA stenosis resolved after successful RV-PAC replacement.

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …

Junctophilin-2 Regulates Mitochondrial Metabolism, Sasha Z Prisco, Lynn M Hartweck, Felipe Kazmirczak, Jenna B Mendelson, Stephanie L Deng, Madelyn Blake, Satadru K Lahiri, Xander H T Wehrens, Kurt W Prins

Faculty, Staff and Students Publications

No abstract provided.

Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou

Faculty, Staff and Students Publications

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care.

METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients(PICU) or high-acuity unit for acute COVID-19 were included.

RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were …

Hyperpolarized Magnetic Resonance Imaging, Nuclear Magnetic Resonance Metabolomics, And Artificial Intelligence To Interrogate The Metabolic Evolution Of Glioblastoma, Kang Lin Hsieh, Qing Chen, Travis C Salzillo, Jian Zhang, Xiaoqian Jiang, Pratip K Bhattacharya, Shyan Shams

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8-16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine models. We further investigated whether artificial intelligence (A.I.) could detect GBM earlier than HPMRS. We developed a deep learning model that combines multiple modalities of cancer data to predict tumor progression, assess treatment effects, and to reconstruct in vivo metabolomic information from ex vivo data. Our model can detect GBM progression two weeks earlier than conventional MRIs …

Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani

Faculty, Staff and Students Publications

UNLABELLED: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant …

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …

Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer

Faculty, Staff and Student Publications

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.

METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …

Cardiac Mass In A 78-Year-Old Patient With A History Of Cancer: Diagnostic And Treatment Challenges, Bihong Zhao, Ayah Zaqqa, Michelle M Mcdonald, Ismael A Salas De Armas, Igor D Gregoric, L Maximilian Buja

The Texas Heart Institute Journal

Primary cardiac angiosarcoma is a rare, aggressive malignancy that commonly metastasizes to various organs. The presenting symptoms are typically nonspecific, so a comprehensive examination is required to confirm the diagnosis promptly. This case report describes the presentation of an older patient with a history of neoplasms. Echocardiography and biopsy were performed, but despite surgical intervention to resect a large right atrial mass, the patient died. A final diagnosis of primary angiosarcoma was made based on the resected specimen.

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …

Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …

Editorial Comment: Diversity And Disparities In Orthopaedic Surgery: Update 2024, Kimberly J Templeton, Melvyn A Harrington

Faculty, Staff and Students Publications

No abstract provided.

Factors Associated With Failed Closed Reduction In Flexion And Gartland Type Iii Pediatric Supracondylar Humerus Fractures, Pablo Coello, Nathaniel Grey Loyd, David A Hsiou, Rachel S Silverstein, Scott B Rosenfeld

Faculty, Staff and Students Publications

Background: Most displaced supracondylar humerus fractures (SCHFs) are treated with closed reduction and percutaneous pinning. While there are only a few possible indications for converting to an open reduction, a failed closed reduction is a common cause. This study aims to elucidate possible risk factors for failed closed reductions of SCHF.

Methods: A retrospective review of SCHF from 2010 to 2020 at a pediatric tertiary medical center, which underwent operative fixation, was conducted. Exclusion criteria were open fractures and reasons for open reduction other than failed closed reduction. Rates of open reduction were assessed by preoperative fracture classification and assessed …