Medicine and Health Sciences Commons^™

Uncontrolled Mitochondrial Calcium Uptake Underlies The Pathogenesis Of Neurodegeneration In Micu1-Deficient Mice And Patients, Raghavendra Singh, Adam Bartok, Melanie Paillard, Ashley L. Tyburski, Melanie B Elliott, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dysregulation of mitochondrial Ca2+ homeostasis has been linked to neurodegenerative diseases. Mitochondrial Ca2+ uptake is mediated via the calcium uniporter complex that is primarily regulated by MICU1, a Ca2+-sensing gatekeeper. Recently, human patients with MICU1 loss-of-function mutations were diagnosed with neuromuscular and cognitive impairments. While studies in patient-derived cells revealed altered mitochondrial calcium signaling, the neuronal pathogenesis was difficult to study. To fill this void, we created a neuron-specific MICU1-KO mouse model. These animals show progressive, abnormal motor and cognitive phenotypes likely caused by the degeneration of motor neurons in the spinal cord and the cortex. We found increased susceptibility …

Recommendations For Daytime, Evening, And Nighttime Indoor Light Exposure To Best Support Physiology, Sleep, And Wakefulness In Healthy Adults, Timothy M Brown, George Brainard, Christian Cajochen, Charles A Czeisler, John P Hanifin, Steven W Lockley, Robert J Lucas, Mirjam Münch, John B O'Hagan, Stuart N Peirson, Luke L A Price, Till Roenneberg, Luc J M Schlangen, Debra J Skene, Manuel Spitschan, Céline Vetter, Phyllis C Zee, Kenneth P Wright

Department of Neurology Faculty Papers

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, …

Multiple Sclerosis: Relationship Between Locus Of Control And Quality Of Life In Persons With Low Versus High Disability, Judith Bijoux Leist, Thomas P. Leist

Department of Neurology Faculty Papers

Background: Health Locus of Control (HLOC) is the degree to which individuals believe that their health outcomes are controlled by 'external' factors - environmental forces, chance, fate, other people, or some higher power - or by 'internal' factors - their own behavior or action. Most of the literature on HLOC associates an Internal Health Locus of Control (IHLOC) to pro-health behaviors and better health outcomes. However, a few studies also suggest that in chronic illnesses, an External Health Locus of Control (EHLOC) could be beneficial with respect to pro-health behaviors and perceptions of Quality of Life (QoL), challenging assumptions about …

Targeting Sox10-Deficient Cells To Reduce The Dormant-Invasive Phenotype State In Melanoma, Claudia Capparelli, Timothy J. Purwin, Mckenna Glasheen, Signe Caksa, Manoela Tiago, Nicole A. Wilski, Danielle Pomante, Sheera Rosenbaum, Mai Q Nguyen, Weijia Cai, Janusz Franco-Barraza, R. Zheng, Md, Gaurav Kumar, I Chervoneva, Ayako Shimada, Vito W Rebecca, Adam E. Snook, Kim Hookim, Xiaowei Xu, Edna Cukierman, Meenhard Herlyn, A E Aplin

Department of Cancer Biology Faculty Papers

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor …

Mutant Lrrk2 In Lymphocytes Regulates Neurodegeneration Via Il-6 In An Inflammatory Model Of Parkinson's Disease, Elena Kozina, Matthew D. Byrne, Richard Jay Smeyne

Department of Neuroscience Faculty Papers

Mutations in a number of genes contribute to development of Parkinson's disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system. Here, using two chimeric mouse models, we demonstrate that: 1) the replacement of mutant LRRK2 with wt form of the protein in T- and B-lymphocytes diminishes LPS-mediated inflammation and rescues the SNpc DA neuron loss in the mutant LRRK2 brain; 2) the presence of G2019S or R1441G LRRK2 mutation in …

Suppression Of Pi3k Signaling Is Linked To Autophagy Activation And The Spatiotemporal Induction Of The Lens Organelle Free Zone, Rifah Gheyas, Ramon Ortega-Alvarez, Daniel Chauss, Marc Kantorow, A. Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The terminal steps of lens cell differentiation require elimination of all organelles to create a central Organelle Free Zone (OFZ) that is required for lens function of focusing images on the retina. Previous studies show that the spatiotemporal elimination of these organelles during development is autophagy-dependent. We now show that the inhibition of PI3K signaling in lens organ culture results in the premature induction of autophagy within 24 h, including a significant increase in LAMP1+ lysosomes, and the removal of lens organelles from the center of the lens. Specific inhibition of just the PI3K/Akt signaling axis was directly linked to …

Clinical Evaluation Of An Auto-Segmentation Tool For Spine Sbrt Treatment., Yingxuan Chen, Yevgeniy Vinogradskiy, Yan Yu, Wenyin Shi, Haisong Liu

Department of Radiation Oncology Faculty Papers

Purpose: Spine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.

Methods: Twenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the …

Clinical Evaluation Of An Auto-Segmentation Tool For Spine Sbrt Treatment, Yingxuan Chen, Yevgeniy Vinogradskiy, Yan Yu, Wenyin Shi, Haisong Lui

Department of Radiation Oncology Faculty Papers

Purpose: Spine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.

Methods: Twenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the …

Characterization Of Basal Ganglia Volume Changes In The Context Of Hiv And Polysubstance Use, Andrew J Monick, Michelle R Joyce, Natasha Chugh, Jason A Creighton, Owen P Morgan, Eric C Strain, Cherie L Marvel

Department of Medicine Faculty Papers

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and …

Detection Of Lung Carcinoma Arising From Ground Glass Opacities (Ggo) After 5 Years - A Retrospective Review, Elissa Herskovitz, Charalamobos Solomides, Julie Barta, Nathaniel R. Evans Iii, Gregory C. Kane

Department of Surgery Faculty Papers

Pure ground glass opacities (GGO) may indicate pre-invasive subtypes of lung carcinoma. These neoplasms typically demonstrate indolent patterns of growth; Fleischner Society guidelines recommend up to five years of serial imaging. Our aim was to determine the frequency of diagnosed carcinoma arising from GGO detected beyond 5 years of surveillance. We reviewed pathologic diagnoses of lung carcinoma (n = 442) between 2016 and 2018 of a tertiary academic hospital and National Cancer Institute-designated cancer center to identify all cancers that arose from ground glass opacities detected on CT scan. Of the 442 cases of lung carcinoma, 32 (7%) were found …

Rare Occurrence Of Pseudomyxoma Peritonei (Pmp) Syndrome Arising From A Malignant Transformed Ovarian Primary Mature Cystic Teratoma Treated By Cytoreductive Surgery And Hipec: A Case Report, Francesca Ponzini, Luke Kowal, Mariam Ghafoor, Allison F Goldberg, Joanna Chan, Ryan Lamm, Shawnna Cannaday, Scott D. Richard, Avinoam Nevler, Harish Lavu, Wilbur Bowne, Norman G Rosenblum

Department of Surgery Faculty Papers

Background: Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered.

Case presentation: Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian …

Cytokines In The Pathogenesis Of Large Granular Lymphocytic Leukemia, Colleen Isabelle, Amy Boles, Nitin Chakravarti, Pierluigi Porcu, Jonathan Brammer, Anjali Mishra

Department of Medical Oncology Faculty Papers

Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. In recent years, it has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. The exact initiation process of LGLL is unknown, although several cytokine-driven mechanisms have emerged. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may also contribute to the co-occurrence of a wide range of autoimmune …

Astrocyte-Secreted Chordin-Like 1 Regulates Spine Density After Ischemic Injury, Elena Blanco-Suarez, Nicola J Allen

Department of Neuroscience Faculty Papers

Ischemic injury occurs when the brain is deprived of blood flow, preventing cells from receiving essential nutrients. The injury core is the brain region directly deprived and is surrounded by the peri-infarct area, the region with recovery potential. In the peri-infarct area neurons undergo acute loss of dendritic spines, which modifies synaptic plasticity and determines neuronal survival. Astrocytes can be protective or detrimental to the ischemic injury response depending on the specific stage, yet we lack clear understanding of the underlying mechanisms. Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse …

T-Cell Responses To Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses To The Colorectal Cancer Antigen, Guanylyl Cyclase C, John C. Flickinger, Jagmohan Singh, Yanki Yarman, Robert D Carlson, Joshua Barton, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Gram-positive bacterium Listeria monocytogenes (Lm) is an emerging platform for cancer immunotherapy. To date, over 30 clinical trials have been initiated testing Lm cancer vaccines across a wide variety of cancers, including lung, cervical, colorectal, and pancreatic. Here, we assessed the immunogenicity of an Lm vaccine against the colorectal tumor antigen GUCY2C (Lm-GUCY2C). Surprisingly, Lm-GUCY2C vaccination did not prime naïve GUCY2C-specific CD8+ T-cell responses towards the dominant H-2Kd-restricted epitope, GUCY2C254-262. However, Lm-GUCY2C produced robust CD8+ T-cell responses towards Lm-derived peptides suggesting that GUCY2C254-262 peptide may be subdominant to Lm-derived peptides. Indeed, incorporating immunogenic Lm peptides into an adenovirus-based GUCY2C …

Chronic Relapsing Neutrophilic Meningitis As The Sole Manifestation Of Nocardiosis In A Patient With Mixed Connective Tissue Disease., M Anthony Albornoz, Erin K Threlfall, Michael Baldassari, Lawrence J Livornese

Department of Neurosurgery Faculty Papers

We describe a rare case of a patient with mixed connective tissue disease maintained on chronic oral corticosteroids, who was hospitalized on five occasions over five consecutive months due to persistent relapsing neutrophilic meningitis caused by Nocardia asteroides. Immunosuppression due to the chronic use of corticosteroids was identified as the underlying mechanism of susceptibility. Our report highlights the challenges associated with systemic Nocardiosis, particularly in the immunocompromised host.

Differential Recognition Of Canonical Nf-Κb Dimers By Importin Α3, Tyler J. Florio, Ravi K Lokareddy, Daniel P Yeggoni, Rajeshwer S Sankhala, Connor A Ott, Richard E Gillilan, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin …

Cloud-Based Ultrasound System: Feasibility And Potential, Ji-Bin Liu

Department of Radiology Faculty Papers

No abstract provided.

Acute Occlusion Of Aortic Endovascular Aneurysm Repair Stent Graft With Bilateral Limb Ischemia, Min Choi, Dawn Salvatore, Paul J Dimuzio, Michael Nooromid, Babak Abai

Department of Surgery Faculty Papers

Endovascular aneurysm repair has dramatically changed the management of abdominal aortic aneurysms as an alternative to open repair. However, complications can occur, including stent graft migration, kinking, and occlusion, leading to compromise of the excluded aneurysm walls and acute limb ischemia. In the present report, we have described a case of migration and kinking of an abdominal aortic stent graft in the main body that led to occlusion of the abdominal aorta and bilateral acute limb ischemia. The patient required emergent explantation of the stent graft and open repair of the abdominal aneurysm with a rifampin-soaked Dacron graft, which achieved …

Aorta In Pathologies May Function As An Immune Organ By Upregulating Secretomes For Immune And Vascular Cell Activation, Differentiation And Trans-Differentiation-Early Secretomes May Serve As Drivers For Trained Immunity, Yifan Lu, Yu Sun, Keman Xu, Fatma Saaoud, Ying Shao, Charles Drummer, Sheng Wu, Wenhui Hu, Jun Yu, Satya P Kunapuli, John R Bethea, Roberto I Vazquez-Padron, Jianxin Sun, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel-Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate …

Laryngeal Blastomycosis With Subsequent Heart Failure From Itraconazole Therapy., Daniel Tsang, S Haddad, Mitchell Sternlieb

Department of Medicine Faculty Papers

Blastomycosis is an endemic mycosis in the United States that typically affects the respiratory tract and presents as a pneumonia. Dissemination can occur to any organ system, most commonly involving the skin or bones. Treatment of blastomycosis depends on the severity of disease and consists of itraconazole with liposomal amphotericin B added in during the initial stage in those with more severe disease or those who are pregnant. This case report describes an immunocompetent individual with mild to moderate blastomycosis of the larynx who was started on itraconazole therapy. However, after two months of treatment, he developed new symptomatic heart …

Rotenone Induces Regionally Distinct Α-Synuclein Protein Aggregation And Activation Of Glia Prior To Loss Of Dopaminergic Neurons In C57bl/6 Mice, Savannah M Rocha, Collin M Bantle, Tawfik Aboellail, Debotri Chatterjee, Richard Jay Smeyne, Ronald B Tjalkens

Department of Neuroscience Faculty Papers

Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes. However, these neuroinflammatory changes have been challenging to study in mice, in part because the systemic rotenone exposure model utilized in rats is more toxic to mice. To establish a reproducible murine …

Association Of Chronic Central Serous Chorioretinopathy With Subclinical Cushing's Syndrome., Rebecca Russ Soares, Annika Samuelson, Allen Chiang

Wills Eye Hospital Papers

Purpose: To report the clinical course of a patient with central serous chorioretinopathy (CSCR) secondary to subclinical hypercortisolism before and after adrenalectomy.

Observations: A 50-year-old female patient with multifocal, chronic CSCR was found to have an adrenal incidentaloma and was diagnosed with subclinical hypercortisolism. Patient elected to undergo minimally-invasive adrenalectomy and presented at 3 months after surgery without subretinal fluid.

Conclusions and importance: Subclinical Cushing's Syndrome (SCS) may present an underrecognized risk factor for developing chronic CSCR. Further investigation is needed to determine the threshold of visual comorbidity that may influence surgical management.

A Review Of Multiomics Platforms In Pituitary Adenoma Pathogenesis, Nikolaos Mouchtouris, Rupert D Smit, Keenan Piper, Giyarpuram Prashant, James J. Evans, Michael Karsy

Department of Neurosurgery Faculty Papers

Pituitary adenomas (PA), or pituitary neuroendocrine tumors (PitNETs), represent 15% of all central nervous system tumors. Classic description of PitNETs solely by hormonal classification has given way to key transcription factors that play a role in the pathology of PitNETs including steroidogenic factor-1 (SF-1), t-box pituitary transcription factor (TPIT), and pituitary transcription factor 1 (PIT-1). Germline mutations in various familial PitNETs are discussed including those in familial isolated pituitary adenoma (FIPA), multiple endocrine neoplasia (MEN), neurofibromatosis 1 (NF1), and Carney complex. Recent advances in next generation sequencing have improved insight into the pathogenesis of PitNETs. A review of key studies …

Prospective Comparison Of Geriatric Assessment And Provider's Assessment Of Older Adults With Metastatic Breast Cancer In The Community, Rino S Seedor, Caitlin R Meeker, Bianca Lewis, Elizabeth A Handorf, Kelly A Filchner, Ramya Varadarajan, Jack Hensold, Aruna Padmanabhan, Benjamin Negin, Kenneth Blankstein, Neha R Chawla, Wei Frank Song, Jessica Epstein, Jennifer Winn, Lori J Goldstein, Efrat Dotan

Department of Medical Oncology Faculty Papers

Background: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP).

Methods: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA.

Results: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of …

Evidence For Paracrine Protective Role Of Exogenous Αa-Crystallin In Retinal Ganglion Cells, Madhu Nath, Zachary B Sluzala, Ashutosh S Phadte, Yang Shan, Angela M Myers, Patrice E Fort

Department of Biochemistry and Molecular Biology Faculty Papers

Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue threonine 148 (T148) and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective …

Impact Of Early Feeding: Metagenomics Analysis Of The Infant Gut Microbiome, Matthew D. Di Guglielmo, Karl R Franke, Alan Robbins, Erin L Crowgey

Department of Pediatrics Faculty Papers

Background: Different feeding regimens in infancy alter the gastrointestinal (gut) microbial environment. The fecal microbiota in turn influences gastrointestinal homeostasis including metabolism, immune function, and extra-/intra-intestinal signaling. Advances in next generation sequencing (NGS) have enhanced our ability to study the gut microbiome of breast-fed (BF) and formula-fed (FF) infants with a data-driven hypothesis approach.

Methods: Next generation sequencing libraries were constructed from fecal samples of BF (n=24) and FF (n=10) infants and sequenced on an Illumina HiSeq 2500. Taxonomic classification of the NGS data was performed using the Sunbeam/Kraken pipeline and a functional analysis at the gene level was performed …

"You Can't Go Wrong Being Safe": Motivations, Patterns, And Context Surrounding Use Of Fentanyl Test Strips For Heroin And Other Drugs., Megan K Reed, Amanda Guth, Venise J Salcedo, Jeffrey K Hom, Kristin L Rising

Department of Emergency Medicine Faculty Papers

BACKGROUND: Unintentional drug overdose fatalities due to fentanyl contamination continue to increase. Fentanyl test strip (FTS) use has emerged as a valuable harm reduction strategy to detect the presence of fentanyl in drugs. However, motivation for FTS uptake and context surrounding use have not been well characterized in the literature. This study aimed to capture people who use drugs' (PWUD) lived experiences to understand motivations underlying FTS uptake, ongoing use, and actions after testing.

METHODS: We conducted qualitative interviews with PWUD at a harm reduction organization in Philadelphia, PA. Interviews asked about experiences with using FTS. Interviews were audio-recorded, professionally …

Human Endothelial Cells Promote Arsenic-Transformed Lung Epithelial Cells To Induce Tumor Growth And Angiogenesis Through Interleukin-8 Induction, Lei Zhao, Yi-Fang Wang, Jie Liu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B …

Clinically Adjudicated Deceased Donor Acute Kidney Injury And Graft Outcomes, Sherry G Mansour, Nadeen Khoury, Ravi Kodali, Sarthak Virmani, Peter P Reese, Isaac E Hall, Yaqi Jia, Yu Yamamoto, Heather R Thiessen-Philbrook, Wassim Obeid, Mona D Doshi, Enver Akalin, Jonathan S Bromberg, Meera N Harhay, Sumit Mohan, Thangamani Muthukumar, Pooja Singh, Francis L Weng, Dennis G Moledina, Jason H Greenberg, Francis P Wilson, Chirag R Parikh

Department of Medicine Faculty Papers

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association.

Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among …

Study Protocol For The Innovative Support For Patients With Sars-Cov-2 Infections Registry (Inspire): A Longitudinal Study Of The Medium And Long-Term Sequelae Of Sars-Cov-2 Infection, Kelli N O'Laughlin, Matthew Thompson, Bala Hota, Michael Gottlieb, Ian D Plumb, Anna Marie Chang, Lauren E Wisk, Aron J Hall, Ralph C Wang, Erica S Spatz, Kari A Stephens, Ryan M Huebinger, Samuel A Mcdonald, Arjun Venkatesh, Nikki Gentile, B. H. Slovis, Mandy Hill, Sharon Saydah, Ahamed H Idris, Robert Rodriguez, Harlan M Krumholz, Joann G Elmore, Robert A Weinstein, Graham Nichol

Department of Emergency Medicine Faculty Papers

Background: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

Methods: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days …