Digital Commons Network^™

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 …

Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee

Faculty, Staff and Students Publications

Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson’s disease, an autosomal recessive disorder that requires life-long medicinal therapy or liver transplantation. Current treatment protocols are limited to either sequestration of copper via chelation or reduction of copper absorption in the gut (zinc therapy). The goal of these strategies is to reduce free copper, redox …

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. …

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 …

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 …

Pax3 Lineage-Specific Deletion Of Gpr161 Is Associated With Spinal Neural Tube And Craniofacial Malformations During Embryonic Development, Sung-Eun Kim, Pooja J Chothani, Rehana Shaik, Westley Pollard, Richard H Finnell

Faculty, Staff and Students Publications

Sonic hedgehog (Shh) signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality associated with craniofacial defects and neural tube defects. However, the structural defects of later embryonic stages and cell lineages underlying abnormalities have not been well characterized due to the limited lifespan of Gpr161 null mice. We found that embryos with Pax3 lineage-specific deletion of Gpr161 presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest), vertebral abnormalities …

Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Bo Zhang, Megan E Washington, I-Wen Song, Lindsay C Burrage, Vittoria C Rossi, Ava S Berrier, Anika Lindsey, Jacob Lesinski, Michael L Nonet, Jian Chen, Dustin Baldridge, Gary A Silverman, V Reid Sutton, Jill A Rosenfeld, Alyssa A Tran, M John Hicks, David R Murdock, Hongzheng Dai, Maryann Weis, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, Richard Caswell, Carrie Pottinger, Deirdre Cilliers, Karen Stals, Undiagnosed Diseases Network, David Eyre, Deborah Krakow, Tim Schedl, Stephen C Pak, Brendan H Lee

Faculty, Staff and Students Publications

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.

METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, …

Biallelic Missense Variants In Cog3 Cause A Congenital Disorder Of Glycosylation With Impairment Of Retrograde Vesicular Trafficking, Ruizhi Duan, Dana Marafi, Zhi-Jie Xia, Bobby G Ng, Reza Maroofian, Farhana Taher Sumya, Ahmed K Saad, Haowei Du, Jawid M Fatih, Jill V Hunter, Hasnaa M Elbendary, Shahid M Baig, Uzma Abdullah, Zafar Ali, Stephanie Efthymiou, David Murphy, Tadahiro Mitani, Marjorie A Withers, Shalini N Jhangiani, Zeynep Coban-Akdemir, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Jennifer E Posey, Henry Houlden, Vladimir V Lupashin, Maha S Zaki, Hudson H Freeze, James R Lupski

Faculty, Staff and Students Publications

Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed …

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 …

Delays In Hepatitis B Immunization Series Completion In People With Human Immunodeficiency Virus, Daanish Sheikh, Kristen A Staggers, Jennifer Carey, Wendy A Keitel, Robert L Atmar, Hana M El Sahly, Jennifer A Whitaker

Faculty, Staff and Students Publications

BACKGROUND: Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV).

METHODS: We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination. …

Baseline Leptin Predicts Response To Metformin In Adolescents With Type 1 Diabetes And Increased Body Mass Index, Heba M Ismail, Souptik Barua, Johnny Wang, Ashutosh Sabharwal, Ingrid Libman, Fida Bacha, Kristen J Nadeau, Mustafa Tosur, Maria J Redondo

Faculty, Staff and Students Publications

No abstract provided.

Endoscopic Vacuum Therapy For Treatment Of Spontaneous And Iatrogenic Upper Gastrointestinal Defects, Kavea Panneerselvam, Jake S Jacob, Ronald E Samuel, Andy Tau, Gyanprakash A Ketwaroo, Wasif M Abidi, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Endoscopic vacuum therapy (EVT) can heal a variety of defects within the gastrointestinal (GI) tract via applying negative pressure, which reduces the defect size, aspirates the infected fluid, and promotes granulation tissue. Here we present our experience with EVT as it relates to both spontaneous and iatrogenic upper GI tract perforations, leaks, and fistulas.

METHODS: This retrospective study was conducted at four large hospital centers. All patients who underwent EVT between June 2018 and March 2021 were included. Data on multiple variables were collected, including demographics, defect size and location, number and intervals of EVT exchanges, technical success, and …

Structural Surfaceomics Reveals An Aml-Specific Conformation Of Integrin Β2 As A Car T Cellular Therapy Target, Kamal Mandal, Gianina Wicaksono, Clinton Yu, Jarrett J Adams, Michael R Hoopmann, William C Temple, Adila Izgutdina, Bonell Patiño Escobar, Maryna Gorelik, Christian H Ihling, Matthew A Nix, Akul Naik, William H Xie, Juwita Hübner, Lisa A Rollins, Sandy M Reid, Emilio Ramos, Corynn Kasap, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Melanie Mcmillan, Victor Gavallos, Andrew D Leavitt, Aaron C Logan, Cliona M Rooney, Justin Eyquem, Andrea Sinz, Benjamin J Huang, Elliot Stieglitz, Catherine C Smith, Robert L Moritz, Sachdev S Sidhu, Lan Huang, Arun P Wiita

Faculty, Staff and Students Publications

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture ‘structural surfaceomics’. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 …

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Thiago Souza Onofre, Kieu T M Pham, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

The unicellular protozoan Trypanosoma brucei has a single flagellum that is involved in cell motility, cell morphogenesis, and cell division. Inheritance of the newly assembled flagellum during the cell cycle requires its correct positioning, which depends on the faithful duplication or segregation of multiple flagellum-associated cytoskeletal structures, including the basal body, the flagellum attachment zone, and the hook complex. Along the flagellum attachment zone sites a set of four microtubules termed the microtubule quartet (MtQ), whose molecular function remains enigmatic. We recently reported that the MtQ-localized protein NHL1 interacts with the microtubule-binding protein TbSpef1 and regulates flagellum inheritance by promoting …

Ewing's Sarcoma Of The Hand: An Unusual Presentation In A Young Hispanic Male, Dylan B Mcbee, Hope A Bentley, Giancarlo Toledanes

Faculty, Staff and Students Publications

Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and …

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 …

Overcoming Barriers To Drug Development And Enrollment In Clinical Trials For Adolescents And Young Adults With Lymphoma, Keri Toner, Carl E Allen, Shweta Jain, Brad Kahl, John Leonard, Heather Wasserstrom, Jonathan W Friedberg, Nita L Seibel, Kara Kelly

Faculty, Staff and Students Publications

Lymphoma is one of the most common cancers in adolescents and young adults, but historically, this population has had lower clinical trial enrollment and improvements in overall survival as compared to other age populations. There are multiple challenges that are unique to this population that have affected drug development and clinical trial enrollment. Our panel of experts have identified barriers, and in this review, we discuss current methods to address these barriers as well as potential solutions moving forward.

Increasing Glutathione Levels By A Novel Posttranslational Mechanism Inhibits Neuronal Hyperexcitability, Ashwini Sri Hari, Rajeswari Banerji, Li-Ping Liang, Ruth E Fulton, Christopher Quoc Huynh, Timothy Fabisiak, Pallavi Bhuyan Mcelroy, James R Roede, Manisha Patel

Faculty, Staff and Students Publications

Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcriptional regulation have been shown to significantly decrease oxidative stress and seizure frequency, increase seizure threshold, and rescue certain cognitive deficits. Whether elevation of GSH per se alters neuronal hyperexcitability remains unanswered. We previously showed that thiols such as dimercaprol (DMP) elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme. Here, we asked if elevation of cellular GSH by DMP altered neuronal hyperexcitability in-vitro and in-vivo. Treatment of …

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 …

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 …

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 …

Diversity, Equity, And Inclusion: Considerations In The Geriatric Emergency Department Patient, Anita N Chary, Lauren Cameron-Comasco, Kalpana N Shankar, Margaret E Samuels-Kalow

Faculty, Staff and Students Publications

This article introduces core topics in health equity scholarship and provides examples of how diversity, equity, and inclusion impact the aging population and emergency care of older adults. It offers strategies for promoting diversity, equity, and inclusion to both strengthen the patient-clinician therapeutic relationship and to address operations and systems that impact care of the geriatric emergency department patient.

Risk-Adjusted Cumulative Sum For Early Detection Of Hospitals With Excess Perioperative Mortality, Vivi W Chen, Alexis P Chidi, Yongquan Dong, Peter A Richardson, David A Axelrod, Laura A Petersen, Nader N Massarweh

Faculty, Staff and Students Publications

IMPORTANCE: National surgical quality improvement programs lack tools for early detection of quality or safety concerns, which risks patient safety because of delayed recognition of poor performance.

OBJECTIVE: To compare the risk-adjusted cumulative sum (CUSUM) with episodic evaluation for early detection of hospitals with excess perioperative mortality.

DESIGN, SETTING, AND PARTICIPANTS: National, observational, hospital-level, comparative effectiveness study of 697 566 patients. Identification of hospitals with excess, risk-adjusted, quarterly 30-day mortality using observed to expected ratios (ie, current criterion standard in the Veterans Affairs Surgical Quality Improvement Program) was compared with the risk-adjusted CUSUM. Patients included in the study underwent a …

Elevated Blood Pressure Accelerates White Matter Brain Aging Among Late Middle-Aged Women: A Mendelian Randomization Study In The Uk Biobank, Li Feng, Zhenyao Ye, Chen Mo, Jingtao Wang, Song Liu, Si Gao, Hongjie Ke, Travis A Canida, Yezhi Pan, Marleen M J Van Greevenbroek, Alfons J H M Houben, Kai Wang, Kathryn S Hatch, Yizhou Ma, David K Y Lei, Chixiang Chen, Braxton D Mitchell, L Elliot Hong, Peter Kochunov, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.

METHODS: In this study, we focused on N  = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity …

The Androgen Receptor Does Not Directly Regulate The Transcription Of Dna Damage Response Genes, Joshua D Samuels, Katelyn A Moore, Hannah E Ennerfelt, Alexis M Johnson, Adeline E Walsh, Richard J Price, John R Lukens

Faculty, Staff and Student Publications

INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.

METHODS: We generated and investigated 5xFAD Inpp5d

RESULTS: SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d

DISCUSSION: …

Use Of Term Reference Infants In Assessing The Developmental Outcome Of Extremely Preterm Infants: Lessons Learned In A Multicenter Study, Charles E Green, Jon E Tyson, Roy J Heyne, Susan R Hintz, Betty R Vohr, Carla M Bann, Abhik Das, Edward F Bell, Sana Boral Debsareea, Emily Stephens, Marie G Gantz, Carolyn M Petrie Huitema, Karen J Johnson, Kristi L Watterberg, Ricardo Mosquera, Myriam Peralta-Carcelen, Deanne E Wilson-Costello, Tarah T Colaizy, Nathalie L Maitre, Stephanie L Merhar, Ira Adams-Chapman, Janell Fuller, Michelle E Hartley-Mcandrew, William F Malcolm, Sarah Winter, Andrea F Duncan, Gary J Myer, Stephen D Kicklighter, Myra H Wyckoff, Sara B Demauro, Anna Maria Hibbs, Barbara J Stoll, Waldemar A Carlo, Krisa P Van Meurs, Matthew A Rysavy, Ravi M Patel, Pablo J Sánchez, Abbot R Laptook, C Michael Cotten, Carl T D'Angio, Michele C Walsh, Human Development Neonatal Research Network

Faculty, Staff and Student Publications

OBJECTIVE: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

STUDY DESIGN: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

RESULTS: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting …

Acaa2 Is A Novel Molecular Indicator For Cancers With Neuroendocrine Phenotype, Michelle Shen, Shiqin Liu, Angus Toland, En-Chi Hsu, Alifiani B Hartono, Busola R Alabi, Merve Aslan, Holly M Nguyen, Conner J Sessions, Rosalie Nolley, Chanjuan Shi, Jiaoti Huang, James D Brooks, Eva Corey, Tanya Stoyanova

Faculty, Staff and Student Publications

BACKGROUND: Neuroendocrine phenotype is commonly associated with therapy resistance and poor prognoses in small-cell neuroendocrine cancers (SCNCs), such as neuroendocrine prostate cancer (NEPC) and small-cell lung cancer (SCLC). Expression levels of current neuroendocrine markers exhibit high case-by-case variability, so multiple markers are used in combination to identify SCNCs. Here, we report that ACAA2 is elevated in SCNCs and is a potential molecular indicator for SCNCs.

METHODS: ACAA2 expressions in tumour xenografts, tissue microarrays (TMAs), and patient tissues from prostate and lung cancers were analysed via immunohistochemistry. ACAA2 mRNA levels in lung and prostate cancer (PC) patients were assessed in published …

The Need For Space To Plan The Future For Spondyloarthritis, Louise D Mccullough

Faculty, Staff and Student Publications

A new study indicates that although men and women are equally likely to experience cognitive impairment after acute ischaemic stroke, there are sex differences in particular cognitive domains. Whether these differences are directly linked to biological sex is uncertain, as many factors, including age and pre-stroke factors, could contribute to cognitive outcomes.

Plasma Biomarkers For Brain Injury In Extracorporeal Membrane Oxygenation, Shrey Kapoor, Anna Kolchinski, Aaron M Gusdon, Lavienraj Premraj, Sung-Min Cho

Faculty, Staff and Student Publications

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiorespiratory failure. Despite its benefits, ECMO carries a significant risk of neurological complications, including acute brain injury (ABI). Although standardized neuromonitoring and neurological care have been shown to improve early detection of ABI, the inability to perform neuroimaging in a timely manner is a major limitation in the accurate diagnosis of neurological complications. Therefore, blood-based biomarkers capable of detecting ongoing brain injury at the bedside are of great clinical significance. This review aims to provide a concise review of the current literature on plasma biomarkers for ABI in …

Biomechanics In The Onset And Severity Of Spondyloarthritis: A Force To Be Reckoned With, Priyanka Iyer, Mark Hwang, Lauren Ridley, Michael M Weisman

Faculty, Staff and Student Publications

Increasing evidence suggests that there is a pivotal role for physical force (mechanotransduction) in the initiation and/or the perpetuation of spondyloarthritis; the review contained herein examines that evidence. Furthermore, we know that damage and inflammation can limit spinal mobility, but is there a cycle created by altered spinal mobility leading to additional damage and inflammation?Over the past several years, mechanotransduction, the mechanism by which mechanical perturbation influences gene expression and cellular behaviour, has recently gained popularity because of emerging data from both animal models and human studies of the pathogenesis of ankylosing spondylitis (AS). In this review, we provide evidence …