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Understanding And Managing Anxiety Sensitivity During Critical Illness And Long-Term Recovery, Leanne M Boehm, Claire M Bird, Ann Marie Warren, Valerie Danesh, Megan M Hosey, Joanne Mcpeake, Kelly M Potter, Han Su, Tammy L Eaton, Mark B Powers Nov 2023

Understanding And Managing Anxiety Sensitivity During Critical Illness And Long-Term Recovery, Leanne M Boehm, Claire M Bird, Ann Marie Warren, Valerie Danesh, Megan M Hosey, Joanne Mcpeake, Kelly M Potter, Han Su, Tammy L Eaton, Mark B Powers

Faculty, Staff and Students Publications

Anxiety sensitivity is a fear of symptoms associated with anxiety (eg, rapid respiration and heart rate, perspiration), also known as "fear of fear." This fear is a misinterpretation of nonthreatening symptoms as threatening across 3 domains: physical ("When my heart rate increases, I'm afraid I may have a heart attack"), social ("If people see me perspire, I fear they will negatively evaluate me"), and cognitive ("When I feel these symptoms, I fear it means I'm going crazy or will lose control and do something dangerous like disconnect my IV"). These thoughts stimulate the sympathetic nervous system, resulting in stronger sensations …


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 Nov 2023

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 …


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 Nov 2023

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.


Ewing's Sarcoma Of The Hand: An Unusual Presentation In A Young Hispanic Male, Dylan B Mcbee, Hope A Bentley, Giancarlo Toledanes Nov 2023

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 …


Clinical Performance Characteristics For Bordered Foam Dressings In The Treatment Of Complex Wounds: An International Wound Dressing Technology Expert Panel Review, Nick Santamaria, Kevin Woo, Dimitri Beeckman, Paulo Alves, Breda Cullen, Amit Gefen, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Andrew Sharpe, Terry Swanson Nov 2023

Clinical Performance Characteristics For Bordered Foam Dressings In The Treatment Of Complex Wounds: An International Wound Dressing Technology Expert Panel Review, Nick Santamaria, Kevin Woo, Dimitri Beeckman, Paulo Alves, Breda Cullen, Amit Gefen, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Andrew Sharpe, Terry Swanson

Center on Aging Staff Publications

The aim of this article is to identify and describe clinical practice performance characteristics for bordered foam dressings in the treatment of complex wounds. Our recently published systematic review of outcomes and applied measurement instruments for the use of bordered foam dressings in complex wounds has led to us identifying a range of important clinical and patient-centred issues related to this dressing class. Specifically, here, we focus on an overview of performance criteria in the areas of application, adhesion, exudate management and debridement functions of bordered foam dressings. Our hope is that by highlighting the clinical performance criteria, future testing …


Valosin-Containing Protein (Vcp/P97) Is Prognostically Unfavorable In Pediatric Aml, And Negatively Correlates With Unfolded Protein Response Proteins Ire1 And Grp78: A Report From The Children’S Oncology Group, Fieke W Hoff, Yihua Qiu, Brandon D Brown, Robert B Gerbing, Amanda R Leonti, Rhonda E Ries, Alan S Gamis, Richard Aplenc, Edward Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Gaye N Jenkins, Terzah M Horton, Steven M Kornblau Nov 2023

Valosin-Containing Protein (Vcp/P97) Is Prognostically Unfavorable In Pediatric Aml, And Negatively Correlates With Unfolded Protein Response Proteins Ire1 And Grp78: A Report From The Children’S Oncology Group, Fieke W Hoff, Yihua Qiu, Brandon D Brown, Robert B Gerbing, Amanda R Leonti, Rhonda E Ries, Alan S Gamis, Richard Aplenc, Edward Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Gaye N Jenkins, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

Purpose: The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML).

Experimental design: Protein expression levels of valosin-containing protein (VCP), a chief element of ERAD, were measured in peripheral blood samples from in 483 pediatric AML patients using reverse phase protein array methodology. Patients participated in the Children's Oncology Group AAML1031 phase 3 clinical trial that randomized patients to standard chemotherapy (cytarabine …


Clinical Efficacy Of Onc201 In H3k27m-Mutant Diffuse Midline Gliomas Is Driven By Disruption Of Integrated Metabolic And Epigenetic Pathways., Sriram Venneti, Abed Rahman Kawakibi, Sunjong Ji, Sebastian M. Waszak, Stefan R. Sweha, Mateus Mota, Matthew Pun, Akash Deogharkar, Chan Chung, Rohinton S. Tarapore, Samuel Ramage, Andrew Chi, Patrick Y. Wen, Isabel Arrillaga-Romany, Tracy T. Batchelor, Nicholas A. Butowski, Ashley Sumrall, Nicole Shonka, Rebecca A. Harrison, John De Groot, Minesh Mehta, Matthew D. Hall, Doured Daghistani, Timothy F. Cloughesy, Benjamin M. Ellingson, Kevin Beccaria, Pascale Varlet, Michelle M. Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Rajan Jain, Maureen Kachman, Heidi Baum, Charles F. Burant, Sophie L. Mottl, Rodrigo T. Cartaxo, Vishal John, Dana Messinger, Tingting Qin, Erik Peterson, Peter Sajjakulnukit, Karthik Ravi, Alyssa Waugh, Dustin Walling, Yujie Ding, Ziyun Xia, Anna Schwendeman, Debra Hawes, Fusheng Yang, Alexander R. Judkins, Daniel Wahl, Costas A. Lyssiotis, Daniel De La Nava, Marta M. Alonso, Augustine Eze, Jasper Spitzer, Susanne V. Schmidt, Ryan J. Duchatel, Matthew D. Dun, Jason E. Cain, Li Jiang, Sylwia A. Stopka, Gerard Baquer, Michael S. Regan, Mariella G. Filbin, Nathalie Y R Agar, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Viveka Nand Yadav, Jacques Grill, Cassie Kline, Sabine Mueller, Adam Resnick, Javad Nazarian, Joshua E. Allen, Yazmin Odia, Sharon L. Gardner, Carl Koschmann Nov 2023

Clinical Efficacy Of Onc201 In H3k27m-Mutant Diffuse Midline Gliomas Is Driven By Disruption Of Integrated Metabolic And Epigenetic Pathways., Sriram Venneti, Abed Rahman Kawakibi, Sunjong Ji, Sebastian M. Waszak, Stefan R. Sweha, Mateus Mota, Matthew Pun, Akash Deogharkar, Chan Chung, Rohinton S. Tarapore, Samuel Ramage, Andrew Chi, Patrick Y. Wen, Isabel Arrillaga-Romany, Tracy T. Batchelor, Nicholas A. Butowski, Ashley Sumrall, Nicole Shonka, Rebecca A. Harrison, John De Groot, Minesh Mehta, Matthew D. Hall, Doured Daghistani, Timothy F. Cloughesy, Benjamin M. Ellingson, Kevin Beccaria, Pascale Varlet, Michelle M. Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Rajan Jain, Maureen Kachman, Heidi Baum, Charles F. Burant, Sophie L. Mottl, Rodrigo T. Cartaxo, Vishal John, Dana Messinger, Tingting Qin, Erik Peterson, Peter Sajjakulnukit, Karthik Ravi, Alyssa Waugh, Dustin Walling, Yujie Ding, Ziyun Xia, Anna Schwendeman, Debra Hawes, Fusheng Yang, Alexander R. Judkins, Daniel Wahl, Costas A. Lyssiotis, Daniel De La Nava, Marta M. Alonso, Augustine Eze, Jasper Spitzer, Susanne V. Schmidt, Ryan J. Duchatel, Matthew D. Dun, Jason E. Cain, Li Jiang, Sylwia A. Stopka, Gerard Baquer, Michael S. Regan, Mariella G. Filbin, Nathalie Y R Agar, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Viveka Nand Yadav, Jacques Grill, Cassie Kline, Sabine Mueller, Adam Resnick, Javad Nazarian, Joshua E. Allen, Yazmin Odia, Sharon L. Gardner, Carl Koschmann

Manuscripts, Articles, Book Chapters and Other Papers

UNLABELLED: Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 …


Interobserver Variability And Challenges In Intraoperative Frozen Section Evaluation Of Pancreatic Margins In Pancreatectomy Specimens, Sadhna Dhingra, Melissa W Taggart, Wai Chin Foo, Asif Rashid, Maria Luisa Machado Heredia, Sarah B May, George Van Buren, William E Fisher, Huamin Wang Nov 2023

Interobserver Variability And Challenges In Intraoperative Frozen Section Evaluation Of Pancreatic Margins In Pancreatectomy Specimens, Sadhna Dhingra, Melissa W Taggart, Wai Chin Foo, Asif Rashid, Maria Luisa Machado Heredia, Sarah B May, George Van Buren, William E Fisher, Huamin Wang

Faculty, Staff and Student Publications

Objective: Frozen-section evaluation of the pancreatic margin is challenging. We aimed to determine interobserver variability among gastrointestinal pathologists for the assessment of frozen sections of pancreatic margins with marked chronic pancreatitis and to determine the challenging histological features in discrepant cases.

Methods: We identified 45 patients who underwent pancreas resection for pancreatic ductal adenocarcinoma and showed marked chronic pancreatitis at pancreatic margin. Deidentified first levels of frozen-sections of the pancreatic margins from all cases were independently reviewed by 5 experienced gastrointestinal pathologists for the presence of carcinoma and/or high-grade dysplasia.

Results: Interobserver agreement among pathologists was calculated as kappa coefficients …


Glut3 Promotes Macrophage Signaling And Function Via Ras-Mediated Endocytosis In Atopic Dermatitis And Wound Healing, Dong-Min Yu, Jiawei Zhao, Eunice E Lee, Dohun Kim, Ruchika Mahapatra, Elysha K Rose, Zhiwei Zhou, Calvin Hosler, Abdullah El Kurdi, Jun-Yong Choe, E Dale Abel, Gerta Hoxhaj, Kenneth D Westover, Raymond J Cho, Jeffrey B Cheng, Richard C Wang Nov 2023

Glut3 Promotes Macrophage Signaling And Function Via Ras-Mediated Endocytosis In Atopic Dermatitis And Wound Healing, Dong-Min Yu, Jiawei Zhao, Eunice E Lee, Dohun Kim, Ruchika Mahapatra, Elysha K Rose, Zhiwei Zhou, Calvin Hosler, Abdullah El Kurdi, Jun-Yong Choe, E Dale Abel, Gerta Hoxhaj, Kenneth D Westover, Raymond J Cho, Jeffrey B Cheng, Richard C Wang

Staff and Researcher Publications

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was …


Cardiac Muscle-Restricted Partial Loss Of Nos1ap Expression Has Limited But Significant Impact On Electrocardiographic Features, Alexa Smith, Dallas Auer, Morgan Johnson, Ernesto Sanchez, Holly Ross, Christopher Ward, Aravinda Chakravarti, Ashish Kapoor Nov 2023

Cardiac Muscle-Restricted Partial Loss Of Nos1ap Expression Has Limited But Significant Impact On Electrocardiographic Features, Alexa Smith, Dallas Auer, Morgan Johnson, Ernesto Sanchez, Holly Ross, Christopher Ward, Aravinda Chakravarti, Ashish Kapoor

Faculty, Staff and Student Publications

Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT …


Human Intestinal Organoids From Cronkhite-Canada Syndrome Patients Reveal Link Between Serotonin And Proliferation, Victoria Poplaski, Carolyn Bomidi, Amal Kambal, Hoa Nguyen-Phuc, Sara C Di Rienzi, Heather A Danhof, Xi-Lei Zeng, Linda A Feagins, Nan Deng, Eduardo Vilar, Florencia Mcallister, Cristian Coarfa, Soyoun Min, Hyun Jung Kim, Richa Shukla, Robert Britton, Mary K Estes, Sarah E Blutt Nov 2023

Human Intestinal Organoids From Cronkhite-Canada Syndrome Patients Reveal Link Between Serotonin And Proliferation, Victoria Poplaski, Carolyn Bomidi, Amal Kambal, Hoa Nguyen-Phuc, Sara C Di Rienzi, Heather A Danhof, Xi-Lei Zeng, Linda A Feagins, Nan Deng, Eduardo Vilar, Florencia Mcallister, Cristian Coarfa, Soyoun Min, Hyun Jung Kim, Richa Shukla, Robert Britton, Mary K Estes, Sarah E Blutt

Faculty, Staff and Student Publications

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation …


Tet2 Modulates Spatial Relocalization Of Heterochromatin In Aged Hematopoietic Stem And Progenitor Cells, Tingting Hong, Jia Li, Lei Guo, Maryn Cavalier, Tianlu Wang, Yaling Dou, Aaron Delafuente, Shaohai Fang, Anna Guzman, Katherina Wohlan, Chiraag Kapadia, Carina Rosas, Yaling Yang, C Cameron Yin, Shaoying Li, M James You, Xiaodong Cheng, Margaret A Goodell, Yubin Zhou, Yun Huang Nov 2023

Tet2 Modulates Spatial Relocalization Of Heterochromatin In Aged Hematopoietic Stem And Progenitor Cells, Tingting Hong, Jia Li, Lei Guo, Maryn Cavalier, Tianlu Wang, Yaling Dou, Aaron Delafuente, Shaohai Fang, Anna Guzman, Katherina Wohlan, Chiraag Kapadia, Carina Rosas, Yaling Yang, C Cameron Yin, Shaoying Li, M James You, Xiaodong Cheng, Margaret A Goodell, Yubin Zhou, Yun Huang

Faculty, Staff and Student Publications

DNA methylation deregulation at partially methylated domains (PMDs) represents an epigenetic signature of aging and cancer, yet the underlying molecular basis and resulting biological consequences remain unresolved. We report herein a mechanistic link between disrupted DNA methylation at PMDs and the spatial relocalization of H3K9me3-marked heterochromatin in aged hematopoietic stem and progenitor cells (HSPCs) or those with impaired DNA methylation. We uncover that TET2 modulates the spatial redistribution of H3K9me3-marked heterochromatin to mediate the upregulation of endogenous retroviruses (ERVs) and interferon-stimulated genes (ISGs), hence contributing to functional decline of aged HSPCs. TET2-deficient HSPCs retain perinuclear distribution of heterochromatin and exhibit …


Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller Nov 2023

Dicarboxylic Acylcarnitine Biomarkers In Peroxisome Biogenesis Disorders, Michael F Wangler, Barbara Lesko, Rejwi Dahal, Sharayu Jangam, Pradnya Bhadane, Theodore E Wilson, Molly Mcpheron, Marcus J Miller

Duncan NRI Faculty and Staff Publications

The peroxisome is an essential eukaryotic organelle with diverse metabolic functions. Inherited peroxisomal disorders are associated with a wide spectrum of clinical outcomes and are broadly divided into two classes, those impacting peroxisome biogenesis (PBD) and those impacting specific peroxisomal factors. Prior studies have indicated a role for acylcarnitine testing in the diagnosis of some peroxisomal diseases through the detection of long chain dicarboxylic acylcarnitine abnormalities (C16-DC and C18-DC). However, there remains limited independent corroboration of these initial findings and acylcarnitine testing for peroxisomal diseases has not been widely adopted in clinical laboratories. To explore the utility of acylcarnitine testing …


Mature B-Cell Lymphomas In Adolescents And Young Adults, Nader Kim El-Mallawany, Lisa Giulino-Roth, John M Burke, Michelle Hermiston, Carl E Allen Nov 2023

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 …


Interplay Between Epigenetic And Genetic Alterations In Inborn Errors Of Immunity, Javier Rodríguez-Ubreva, Celia L Calvillo, Lisa R Forbes Satter, Esteban Ballestar Nov 2023

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 …


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 Nov 2023

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 …


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 Nov 2023

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 Nov 2023

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 …


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 Nov 2023

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 …


Pediatric Microsurgery And Free-Tissue Transfer, Heather R Burns, Anna J Skochdopole, Richardo Alfaro Zeledon, William C Pederson Nov 2023

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.


Site-Specific Pathophysiology In A Neonatal Mouse Model Of Gastroparesis, Price T Edwards, Krishnakant G Soni, Margaret E Conner, Stephanie W Fowler, Jaime P P Foong, Rhian Stavely, Lily S Cheng, Geoffrey A Preidis Nov 2023

Site-Specific Pathophysiology In A Neonatal Mouse Model Of Gastroparesis, Price T Edwards, Krishnakant G Soni, Margaret E Conner, Stephanie W Fowler, Jaime P P Foong, Rhian Stavely, Lily S Cheng, Geoffrey A Preidis

Faculty, Staff and Students Publications

BACKGROUND: Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.

METHODS: Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light …


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 Nov 2023

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

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to …


Research Priorities For Pediatric Emergency Care To Address Disparities By Race, Ethnicity, And Language, Elyse N Portillo, Chris A Rees, Emily A Hartford, Zachary C Foughty, Michelle L Pickett, Colleen K Gutman, Bashar S Shihabuddin, Eric W Fleegler, Corrie E Chumpitazi, Tiffani J Johnson, David Schnadower, Kathy N Shaw Nov 2023

Research Priorities For Pediatric Emergency Care To Address Disparities By Race, Ethnicity, And Language, Elyse N Portillo, Chris A Rees, Emily A Hartford, Zachary C Foughty, Michelle L Pickett, Colleen K Gutman, Bashar S Shihabuddin, Eric W Fleegler, Corrie E Chumpitazi, Tiffani J Johnson, David Schnadower, Kathy N Shaw

Faculty, Staff and Students Publications

IMPORTANCE: Health care disparities are well-documented among children based on race, ethnicity, and language for care. An agenda that outlines research priorities for disparities in pediatric emergency care (PEC) is lacking.

OBJECTIVE: To investigate research priorities for disparities in PEC among medical personnel, researchers, and health care-affiliated community organizations.

DESIGN, SETTING, AND PARTICIPANTS: In this survey study, a modified Delphi approach was used to investigate research priorities for disparities in PEC. An initial list of research priorities was developed by a group of experienced PEC investigators in 2021. Partners iteratively assessed the list through 2 rounds of electronic surveys using …


Limited Clinical Utility Of Routine Mycobacterial Cultures For The Management Of Diabetic Foot Infections, Laila M. Castellino, Clare Mccormick-Baw, Tyler Coye, Peter A. Crisologo, John J. Hanna, Francesca Lee, Andrew Clark, Michael Fanning, Amanda L. Killeen Nov 2023

Limited Clinical Utility Of Routine Mycobacterial Cultures For The Management Of Diabetic Foot Infections, Laila M. Castellino, Clare Mccormick-Baw, Tyler Coye, Peter A. Crisologo, John J. Hanna, Francesca Lee, Andrew Clark, Michael Fanning, Amanda L. Killeen

School of Podiatric Medicine Publications

Mycobacterial infections of the foot and ankle are uncommon. In a cohort of 2340 patients with diabetic foot infection (DFI) in a region with increased prevalence of mycobacterial disease, we identified no clinically significant positive cultures over a 3-year period. Routine mycobacterial culture of DFIs is of limited clinical utility.


Building Up A Genomic Surveillance Platform For Sars-Cov-2 In The Middle Of A Pandemic: A True North-South Collaboration, Waqasuddin Khan, Furqan Kabir, Samiah Kanwar, Fatima Aziz, Sahrish Muneer, Adil Kalam, Mehdia Ali, Nadia Ansari, Fyezah Jehan, Muhammad Imran Nisar Nov 2023

Building Up A Genomic Surveillance Platform For Sars-Cov-2 In The Middle Of A Pandemic: A True North-South Collaboration, Waqasuddin Khan, Furqan Kabir, Samiah Kanwar, Fatima Aziz, Sahrish Muneer, Adil Kalam, Mehdia Ali, Nadia Ansari, Fyezah Jehan, Muhammad Imran Nisar

Department of Paediatrics and Child Health

Next-generation sequencing technology has revolutionised pathogen surveillance over the last two decades. However, the benefits are not equitably distributed, with developing countries lagging far behind in acquiring the required technology and analytical capacity. Recent declines in the cost associated with sequencing-equipment and running consumables have created an opportunity for broader adoption. During the COVID-19 pandemic, rapid diagnostics development and DNA sequencing revolutionised the ability to diagnose and sequence SARS-CoV-2 rapidly. Socioeconomic inequalities substantially impact the ability to sequence SARS-CoV-2 strains and undermine a developing country's pandemic preparedness. Low- and middle-income countries face additional challenges in establishing, maintaining and expanding genomic …


Subungual Squamous Cell Carcinoma Leading To Arm Amputation, Ovidiu V. Fabian, Emilia Maria Pătruţ, Mădălina Șteţca, Radu Mircea Galasiu, Vlad Zolog, Adriana Zolog, Iacob Domşa, Ioan Șimon, Anca Mihailov, Olga Hilda Orăşan, Flaviu Mureşan Oct 2023

Subungual Squamous Cell Carcinoma Leading To Arm Amputation, Ovidiu V. Fabian, Emilia Maria Pătruţ, Mădălina Șteţca, Radu Mircea Galasiu, Vlad Zolog, Adriana Zolog, Iacob Domşa, Ioan Șimon, Anca Mihailov, Olga Hilda Orăşan, Flaviu Mureşan

Journal of Mind and Medical Sciences

Although rare, subungual carcinoma is the most common malignant nail tumor. The symptomatology is not characteristic, being very similar to that of other nail and periungual diseases. For this reason, early diagnosis is usually established by performing a biopsy. With appropriate treatment, subungual carcinoma usually has a favorable prognosis. Metastatic cases are rarely encountered, but they usually have a poor therapeutic result. This article presents the case of a patient with subungual carcinoma (diagnosed by histopathological exam), initially treated by amputation of the distal and middle phalanges of the fourth finger. Two years after the operation, a recurrence in the …


Giant Renal Cell Carcinoma In A Patient With Ipsilateral Lower Limb Hypertrophic Lichen Planus; Case Report And Literature Review, Silvia Popescu, Dumitru Peța, Zoltan Janos Kövér, Dumitru Toma, Ioan-Teodor Cristea, Mihaela Anca Popescu, Oana-Denisa Bălălău, Romina-Marina Sima, Gabriel-Petre Gorecki, Călin Giurcăneanu Oct 2023

Giant Renal Cell Carcinoma In A Patient With Ipsilateral Lower Limb Hypertrophic Lichen Planus; Case Report And Literature Review, Silvia Popescu, Dumitru Peța, Zoltan Janos Kövér, Dumitru Toma, Ioan-Teodor Cristea, Mihaela Anca Popescu, Oana-Denisa Bălălău, Romina-Marina Sima, Gabriel-Petre Gorecki, Călin Giurcăneanu

Journal of Mind and Medical Sciences

Renal cell carcinoma is the most common type of primary urogenital cancer, usually resistant to radiotherapy and chemotherapy. Hypertrophic lichen planus is an inflammatory dermatosis characterized by the presence of papulosquamous and intensely pruritic lesions. The association of these two conditions is unusual, being reported in the specialized literature only in a few rare cases with the onset of lichenoid lesions after patients have undergone various forms of treatment. The case of a 62-year-old male patient who was admitted for severe abdominal pain due to a giant renal tumor associated with a hypertrophic plaque located on the anterior part of …


Prevalence Of Comorbidities And Survival Analysis Of Covid-19 Patients – An Observational Study From A Tertiary Healthcare Center In North West Romania, Mihaela Simona Popoviciu, Lorena Paduraru, Roxana Adriana Stoica, Anca Pantea Stoian, Claudiu Teodorescu, Simona Cavalu Oct 2023

Prevalence Of Comorbidities And Survival Analysis Of Covid-19 Patients – An Observational Study From A Tertiary Healthcare Center In North West Romania, Mihaela Simona Popoviciu, Lorena Paduraru, Roxana Adriana Stoica, Anca Pantea Stoian, Claudiu Teodorescu, Simona Cavalu

Journal of Mind and Medical Sciences

Objectives. The experience accumulated in the last two years shows that the prevention of COVID-19 in people with comorbidities (protective measures, vaccination, etc.) still remains a public health priority. In this context, the aim of our study was to perform a retrospective, observational study in order to assess the time-to-death and risk factors of mortality among COVID-19 patients. Materials and Methods. The study was conducted on 177 patients admitted to Oradea Emergency County Hospital, Bihor, Romania, between October and December 2021. Inclusion criteria were patients over 18 years positive for COVID-19 in upper respiratory tract samples using real-time PCR test. …


Revascularization Impact: Quality Of Life Enhancement In Chronic Limb-Threatening Ischemia, Cristian Traian Paius, Vlad Denis Constantin, Alexandru Carap, Andrei Tarus, Grigore Tinica Oct 2023

Revascularization Impact: Quality Of Life Enhancement In Chronic Limb-Threatening Ischemia, Cristian Traian Paius, Vlad Denis Constantin, Alexandru Carap, Andrei Tarus, Grigore Tinica

Journal of Mind and Medical Sciences

Introduction. Globally, over 230 million people have peripheral artery disease, often undiagnosed, leading to chronic limb-threatening ischemia. Revascularization is vital for preventing amputation and improving quality of life. While specific questionnaires for severe ischemia are lacking, the SF-36 questionnaire is widely used to assess quality of life, with variations like SF-12 and SF-8 for larger cohorts. Objectives. Our aim was to assess how different lower limb revascularization methods affect the postoperative quality of life in patients with chronic limb-threatening ischemia. Methods. This study was conducted at the St. Pantelimon Emergency Hospital of Bucharest, Romania. It included 166 adult patients with …


Follow-Up Care After Metabolic Surgery – A Prospective Study In The North-Eastern Region Of Romania, Sorina Boariu, Ana Maria Scutariu, Adrian Cureniuc, Anamaria Meuca, Roxana Adriana Stoica, Anca Mihaela Pantea Stoian, Delia Reurean Pintilei Oct 2023

Follow-Up Care After Metabolic Surgery – A Prospective Study In The North-Eastern Region Of Romania, Sorina Boariu, Ana Maria Scutariu, Adrian Cureniuc, Anamaria Meuca, Roxana Adriana Stoica, Anca Mihaela Pantea Stoian, Delia Reurean Pintilei

Journal of Mind and Medical Sciences

Background. Anti-obesity therapeutic strategies are continuously evolving. Bariatric procedures or metabolic surgery are among the most effective and long-lasting therapies for obesity and its complications. Our objective was to investigate the clinical and biological evolution after metabolic surgery in a group of patients from North-Eastern Romania and to evaluate a nutritional intervention plan for this population. Materials and Methods. Our clinic surveyed 50 patients who received nutritional counselling before and after bariatric surgery. The patient's weight loss, metabolic markers, and lifestyle changes from January to December 2021 were recorded. SPSS Statistics v.18 was used for statistical analyses. Results and Discussions. …