Medical Specialties Commons^™

Predictors Of Failure To Rescue After Fenestrated-Branched Endovascular Aortic Repair Of Thoracoabdominal Aortic Aneurysms: Presented At The Thirty-Seventh Annual Meeting Of The European Society Of Vascular Surgery, Belfast, Northern Ireland, September 26-29, 2023, Andrea Vacirca, Thomas Mesnard, Ying Huang, Bernardo C Mendes, Tomasz Jakimowicz, Darren B Schneider, Stéphan Haulon, Jonathan Sobocinski, Adam W Beck, Andres Schanzer, Mark A Farber, Carlos Timaran, Andrea Kahlberg, Tilo Kölbel, Warren J Gasper, Barend M E Mees, Mauro Gargiulo, Nuno V Dias, Anthony Lee Woongchae, Matthew P Sweet, Kevin Mani, Matthew Eagleton, Luis Mendes Pedro, Hence Verhagen, Kak Khee Yeung, Nikolaos Tsilimparis, Timothy Resch, Luca Bertoglio, Emília Ferreira, Manar Khashram, Titia Sulzer, Marina Dias-Neto, Emanuel R Tenorio, Lucas Ruiter Kanamori, Katarzyna Jama, Ezequiel Parodi, Vivian Gomes, Jesus Porras Colon, Roberto Chiesa, Giuseppe Panuccio, Geert Willem Schurink, Charlotte Lemmens, Enrico Gallitto, Gianluca Faggioli, Angelos Karelis, Anders Wanhainen, Mohammed Habib, Ryan Gouveia E Melo, Kaj Olav Kappe, Samira Elize Mariko Van Knippenberg, Bichlan Tran, Sean Crawford, Marco Panagrosso, Andrea Melloni, Stefano Bonardelli, Rita Garcia, Tiago Ribeiro, Sinead Gormley, Steven Maximus, Gustavo S Oderich, International Multicenter Aortic Research Group

Faculty, Staff and Students Publications

No abstract provided.

Role Of Kctd13 In Modulating Ar And Sox9 Expression In Different Penile Cell Populations, Carolina J Jorgez, Ahmed Chahdi, Hunter Flores, Marisol O'Neill, Abhishek Seth

Faculty, Staff and Students Publications

Objective: Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. Kctd13-knockout (Kctd13-KO) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the Kctd13-KO penis could help us to understand the mechanism of action of these signaling pathways on penile development.

Methods: We generated transgenic mice lacking Kctd13 and conditionally expressing AR in the urethral mesenchyme after Cre activation with Twist2cre (Kctd13-KO; AR-CMV; Twist2cre; herein called AR+), and Sox9 in the urethral …

Mechanisms Of Change In Exposure Therapy For Anxiety And Related Disorders: A Research Agenda, Kristen Benito, Andre Pittig, Jonathan Abramowitz, Joanna J Arch, Denise Chavira, Rianne De Kleine, Alessandro S De Nadai, Dirk Hermans, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, Katharina Kircanski, Peter M Mcevoy, Heidi Meyer, Marie-H Monfils, Santiago Papini, Winfried Rief, David Rosenfield, Eric A Storch, Michael J Telch, Michael W Otto, Jasper A J Smits

Faculty, Staff and Students Publications

Anxiety and related disorders are a significant public health burden with rising prevalence in the wake of the COVID-19 pandemic. As demand for effective anxiety treatment increases, so too does the need for strategies to bolster treatment outcomes. Research on the mechanisms of exposure therapy, the frontline behavioral treatment, will be critically important for optimizing clinical outcomes. We outline an initial agenda for future research on the mechanisms of change of exposure therapy, developed in collaboration with a large international team of researchers through the Exposure Therapy Consortium (ETC). Key questions and recommendations for future research focus on five priority …

Tissue Engineering: History, Principles, Applications, Challenges, And Future Work, Alexa Cesari, Ms

Student Papers, Posters & Projects

Tissue engineering is a comprehensive and cutting-edge field that leverages principles from multiple scientific disciplines to assist in regenerative medicine. It is defined by the most basic structure of the human body, the cell. When an injury occurs, cells send signals to initiate wound healing processes. In most cases, the body is equipped to heal wounds on its own; however, there are instances where wounds are too severe and cannot undergo proper regeneration. When this occurs, alternative measures are taken to assist in wound repair. With numerous advancements made over the years, tissue engineering has become an increasingly common method …

Inflammatory Bowel Disease: Patient Journey And Cancer Pathology, Katie Contino, Ms

Student Papers, Posters & Projects

Inflammatory Bowel Disease is a relapsing-remitting autoimmune disease that affects the gastrointestinal tract. It consists of Crohn’s disease, which can affect the entire gastrointestinal system, and ulcerative colitis, which is limited to the colon. Inflammatory Bowel Disease has various different levels of severity that have different treatment and medication options once the diagnosis is confirmed with an endoscopic procedure. The treatment options range from daily medication to invasive surgical procedures. Specific diets are also used as a preventative measure to remain in remission. The intestinal damage inflicted to the epithelium increases the risk of developing colon cancer, specifically those with …

Identification Of Distinct Biological Groups Of Patients With Cryptogenic Norse Via Inflammatory Profiling, Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin

Faculty, Staff and Students Publications

Background and objectives: Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms. The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.

Methods: Sixty-two patients with c-NORSE were included. A comprehensive panel …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

A Late Presentation Of Benign Cephalic Histiocytosis, Madison A. Hackley, Nicholas D. Brownstone, Shayan Waseh, Simo Huang, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

Implementing A Stakeholder-Informed Approach For Standardized Collection Of Sexual Orientation And Gender Identity Data: Lessons Learned At A Matrix Comprehensive Cancer Center, Susan L Parker, Montserrat Ayala-Ramirez, Jane R Montealegre, Michael E Scheurer

Faculty, Staff and Students Publications

This brief report describes takeaways from the implementation of sexual orientation and gender identity (SOGI) data collection within a matrix comprehensive cancer center. Implementation of standardized and parsimonious SOGI data collection practices is a strategy recommended to improve our understanding of the cancer experiences among sexual and gender minority (SGM) populations. However, interventions are rarely sustained in routine practice without an organized program to support their implementation. We used a stakeholder-engaged approach to integrate a SOGI questionnaire in the electronic health record (EHR) at Dan L Duncan Comprehensive Cancer Center (DLDCCC)-affiliated adult oncology clinics and evaluate its feasibility, acceptability, and …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

Distinguishing Pex2 And Pex16 Gene Variant Severity For Mild, Severe And Atypical Peroxisome Biogenesis Disorders, Vanessa A Gomez, Oguz Kanca, Sharayu V Jangam, Saurabh Srivastav, Jonathan C Andrews, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Peroxisomal biogenesis disorders (PBD) are autosomal recessive diseases caused by mutations in specific PEX genes that impair peroxisome formation, leading to multi-systemic failure. Symptoms vary, even in patients with variants in the same PEX gene. Our goal is to select PEX mutations and use Drosophila to model a severity spectrum based on genotype-phenotype correlations. Utilizing KozakGAL4 (KZ) cassettes, we replaced the coding sequence of Pex with a GAL4 driver, ideal for making 'humanized' flies in which human PEX can replace the fly loss. We generated Pex2KZ and Pex16KZ lines and assessed them in various behavior assays, confirming their severe phenotypes. …

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Gut Virome Profile In New Onset Treatment Naïve Saudi Children With Ulcerative Colitis, Mohammad El Mouzan, Tor C Savidge, Ahmed Al Sarkhy, Shyam Badu, Badr Alsaleem, Mohammad Al Mofarreh, Abdullah Almasood, Asaad Assiri

Faculty, Staff and Students Publications

Background: Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.

Methods: Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-naïve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal …

Short-Term Neurologic Outcomes In Pediatric Extracorporeal Membrane Oxygenation Are Proportional To Bleeding Severity Graded By A Novel Bleeding Scale, Katherine Doane, Danielle Guffey, Laura L Loftis, Trung C Nguyen, Matthew A Musick, Amanda Ruth, Ryan D Coleman, Jun Teruya, Christine Allen, Melania M Bembea, Brian Boville, Jamie Furlong-Dillard, Santosh Kaipa, Mara Leimanis, Matthew P Malone, Lindsey K Rasmussen, Ahmed Said, Marie E Steiner, Deanna T Tzanetos, Heather Viamonte, Linda Wallenkamp, Arun Saini

Faculty, Staff and Students Publications

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2–18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days …

Mycetohabitans Rhizoxinica Bacteremia In The Setting Of Invasive Fungal Disease In An Immunocompromised Patient, Marisa Orbea, Mary Fortini, Megan H Amerson-Brown, Debra L Palazzi, James J Dunn

Faculty, Staff and Students Publications

Background: Mycetohabitans [Burkholderia] rhizoxinica is an endosymbiotic bacteria of Rhizopus microsporus that normally causes rice seedling blight. In our case report, we present one of the first known cases of concomitant bacteremia with M. rhizoxinica and invasive mold infection due to Rhizopus spp. in an immunocompromised child.

Case summary: A 3 year old male recently diagnosed with B-cell acute lymphoblastic leukemia developed febrile neutropenia. His workup was significant for invasive fungal sinusitis due to Exserohilum spp. based on histopathology and culture, a right middle lobe infiltrate, and a blood culture positive for gram-negative coccobacilli, later identified as M. …

A Lysosomal Surveillance Response To Stress Extends Healthspan, Terytty Yang Li, Arwen W Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J Liu, Rachel N Arey, Kimberly Morales, Raya B Liu, Wenzheng Wang, Ang Zhou, Tong-Jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H Houtkooper, Johan Auwerx

Faculty, Staff and Students Publications

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H+-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

A Hypomorphic Model Of Cps1 Deficiency For Investigating The Effects Of Hyperammonemia On The Developing Nervous System, Stuti Bakshi, Taryn Diep, Brandon J Willis, Rachel Reyes, Grace F Wu, Georgios Makris, Martin Poms, Isabel Day, Qin Sun, Irina Zhuravka, Lindsay Lueptow, Michelle Tang, Gareth A Cromie, Aimée M Dudley, Johannes Häberle, Gerald S Lipshutz

Faculty, Staff and Students Publications

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare metabolic disorder that, in neonatal onset, is typically characterized by severe life-threatening and neurologically injuring hyperammonemic episodes with high unmet patient need. Patients that retain limited enzyme activity may present later in life with less severe hyperammonemia. CPS1 drives the first step in the urea cycle, the pathway terrestrial mammals utilize to metabolize nitrogen. In order to probe the effect of hyperammonemia on the developing nervous system and explore new therapies, a murine Cps1 exon 3-4 mutant was previously generated. However, these mice die within 24 h of birth, limiting study …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Formation Of An Expanding Memory Representation In The Hippocampus, Sachin P Vaidya, Guanchun Li, Raymond A Chitwood, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with …

A Survey Study Of Roadblocks In Translational Science, Fasiha Kanwal, Christopher I Amos, Katherine H Sippel, Claudia Neuhauser, Ariel Harrison, Mary E Dickinson, Charles Minard, Bettina M Beech

Faculty, Staff and Students Publications

Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks …

Cardiovascular-Kidney-Metabolic Effects: Steroidal And Nonsteroidal Mineralocorticoid Receptor Antagonists, Biykem Bozkurt, James L Januzzi, Shweta Bansal

Faculty, Staff and Students Publications

Cardiovascular (CV)-kidney-metabolic (CKM) syndrome is a complex disorder characterized by the co-occurrence of CV risk factors, including chronic kidney disease (CKD), hypertension, and metabolic dysfunction, which creates a vicious cycle where one factor negatively impacts the others, ultimately leading to poor overall CV and kidney outcomes. Overactivation of the mineralocorticoid receptor, through binding with aldosterone and ligand-independent mechanisms, is implicated in the pathogenesis of CKM; mineralocorticoid receptor antagonists (MRAs) can block this interaction. Steroidal MRAs are currently recommended for people with heart failure (HF) with reduced ejection fraction and hypertension; however, the role of nonsteroidal MRAs in CKM is evolving. …

Cardiac Rhythm Devices In Heart Failure With Reduced Ejection Fraction – Role, Timing, And Optimal Use In Contemporary Practice European Journal Of Heart Failure Expert Consensus Document, Biykem Bozkurt, Wilfried Mullens, Christophe Leclercq, Andrea M Russo, Gianluigi Savarese, Michael Böhm, Loreena Hill, Koichiro Kinugawa, Naoki Sato, William T Abraham, Antoni Bayes-Genis, Alexandre Mebazaa, Giuseppe M C Rosano, Shelley Zieroth, Cecilia Linde, Javed Butler

Faculty, Staff and Students Publications

Guidelines for management of heart failure with reduced ejection fraction (HFrEF) emphasize personalized care, patient engagement, and shared decision-making. Medications and cardiac rhythm management (CRM) devices are recommended with a high level of evidence. However, there are significant disparities: patients who could benefit from devices are frequently referred too late or not at all. Misconceptions about device therapy and the notion that the needs of patients (especially the prevention of sudden cardiac death) can now be met by expanding drug therapies may play a role in these disparities. This state-of-the-art review is produced by members of the DIRECT HF initiative, …

Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation And Heart Failure With Diastolic Dysfunction, Luge Li, Cristian Coarfa, Yue Yuan, Issam Abu-Taha, Xiaolei Wang, Jia Song, Yuying Zeng, Xiaohui Chen, Amrit Koirala, Sandra L Grimm, Markus Kamler, Lisa K Mcclendon, Michelle Tallquist, Stanley Nattel, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Atrial fibrillation (AF) often coexists with heart failure, both involving inflammatory signaling and cardiac fibroblasts. To understand the role of fibroblast NLR family pyrin domain containing 3 (NLRP3) inflammasome in cardiac function, we found that NLRP3 was up-regulated in atrial fibroblasts from AF patients. Fibroblast-specific activation of NLRP3 in mice induced AF-promoting atrial myopathy and heart failure with diastolic dysfunction, accompanied by increased fibrosis, and reduced conduction velocity. Knockdown of NLRP3 prevented the AF-promoting atrial substrate and cardiomyopathy in the context of NLRP3 activation in fibroblasts. We identify the fibroblast NLRP3 inflammasome as a key pathway governing the promotion of …

Dichotomous Roles Of Acbd3 In Nsclc Growth And Metastasis, Xiaochao Tan, Chao Wu, Priyam Banerjee, Shike Wang, Derrick L Cardin, Yuting Xu, Chad J Creighton, William K Russell

Faculty, Staff and Students Publications

Lung cancer continues to be the leading cause of cancer-related deaths globally. Unraveling the regulators behind lung cancer growth and its metastatic spread, along with understanding the underlying mechanisms, is crucial for developing novel and effective therapeutic strategies. While much research has focused on identifying potential oncogenes or tumor suppressors, the roles of certain genes can vary depending on the context and may even exhibit contradictory effects. In this study, we demonstrate that acyl-CoA binding domain containing 3 (ACBD3), a Golgi resident protein, promotes primary lung cancer growth by recruiting phosphatidylinositol (PI)-4-kinase IIIβ (PI4KB) to the Golgi, thereby enhancing oncogenic …