Medical Specialties Commons^™

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as …

Atrial Shunt Therapy For Heart Failure: An Update, William Gray

Department of Medicine Faculty Papers

Transcatheter atrial shunt therapies, designed to dynamically lower left atrial (LA) pressure by shunting blood into the larger reservoir of the right atrium and central veins, have been developed as a novel treatment for heart failure (HF) over the past 10+ years. Several atrial shunt devices and procedures are currently in development with several pivotal randomized clinical trials (RCT) underway; however, only 2 sham-controlled RCT (both with the Atrial Shunt Device [Corvia Medical] in HF with EF ≥ 40%) have been reported thus far; a mechanistic RCT (n = 44) that demonstrated a reduction in exercise LA pressure at …

The Role And Outcomes Of Thoracodistal Bypass, Andrea Mcsweeny, Anthony Feghali, Tuong Nguyen, Michael Nooromid, Dawn Salvatore, Paul Dimuzio, Babak Abai

Department of Surgery Faculty Papers

Objectives

Endovascular procedures for lower extremity revascularization are becoming more commonplace due to low morbidity, mortality, and shorter length of stay. The role of open bypass must be reconsidered. Aortobifemoral bypass is the gold standard for extensive aortoiliac occlusive disease (AIOD); however, thoracodistal bypass holds a niche position. We investigate indications and outcomes of thoracodistal bypass.

Methods

Medical records of five patients who underwent thoracodistal bypass at Thomas Jefferson University Hospital (TJUH) between 2012 and 2019 were reviewed. Contemporary and historical literature was reviewed.

Results

Indications included calcified paravisceral pathology, previous failed or infected bypass grafts, and prior abdominal operations. …

Hepatic Lipocalin 2 Promotes Liver Fibrosis And Portal Hypertension, Jiegen Chen, Josepmaria Argemi, Gemma Odena, Ming-Jiang Xu, Yan Cai, Veronica Massey, Austin Parrish, Rajanikanth Vadigepalli, Jose Altamirano, Joaquin Cabezas, Pere Gines, Juan Caballeria, Natasha Snider, Pau Sancho-Bru, Shizuo Akira, Ivan Rusyn, Bin Gao, Ramon Bataller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2−/− mice were protected from liver …

Regulation Of Microrna-497-Targeting Akt2 Influences Tumor Growth And Chemoresistance To Cisplatin In Lung Cancer., Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Jian-Ge Qiu, Feng-Mei Zhou, Wen-Jing Liu, Di-Di Wan, Marie Chai-Mi Lin, Ling-Zhi Liu, Jian-Ying Zhang, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear.

Methods: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was …

Quantification Of Lactoyl-Coa (Lactyl-Coa) By Liquid Chromatography Mass Spectrometry In Mammalian Cells And Tissues., Erika L Varner, Sophie Trefely, David Bartee, Eliana Von Krusenstiern, Luke Izzo, Carmen Bekeova, Roddy S O'Connor, Erin L Seifert, Kathryn E Wellen, Jordan L Meier, Nathaniel W Snyder

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Lysine lactoylation is a recently described protein post-translational modification (PTM). However, the biochemical pathways responsible for this acylation remain unclear. Two metabolite-dependent mechanisms have been proposed: enzymatic histone lysine lactoylation derived from lactoyl-coenzyme A (lactoyl-CoA, also termed lactyl-CoA), and non-enzymatic lysine lactoylation resulting from acyl-transfer via lactoyl-glutathione. While the former has precedent in the form of enzyme-catalysed lysine acylation, the lactoyl-CoA metabolite has not been previously quantified in mammalian systems. Here, we use liquid chromatography-high-resolution mass spectrometry (LC-HRMS) together with a synthetic standard to detect and validate the presence of lactoyl-CoA in cell and tissue samples. Conducting a retrospective analysis …

Conceptualization Of A Parasympathetic Endocrine System., Jonathan Gorky, James Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We here propose a parasympathetic endocrine system (PES) comprised of circulating peptides released from secretory cells in the gut, significantly modulated by vagal projections from the dorsal motor nucleus of the vagus (DMV). While most of these gut peptides mediate well-described satiety and digestive effects that increase parasympathetic control of digestion (Lee et al., 1994; Gutzwiller et al., 1999; Klok et al., 2007), they also have actions that are far-reaching and increase parasympathetic signaling broadly throughout the body. The actions beyond satiety that peptides like somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide have been well-examined, but not in …

3d Printed Biliary Anatomy For Surgical Planning, Jason Core, Erik Massenzio, Tamar Wasserman, Kevin Xie

Phase 1

Background: Studies demonstrated that 3D-printed livers from CT or MRI data can be accurate models of actual patient anatomy. However, it has yet to be established if 3D printing offers improvements to clinical outcomes in surgery. This project seeks to optimize these applications for use at Jefferson by producing 3D-printed models from patient CT scans to guide liver resection surgeries.

Methods: A liver transplant attending was interviewed about challenges encountered during hepatectomies. A publicly available abdominal computed tomography scan was used to render a liver and its vasculature in 3DSlicer. The liver surface was cut into two halves in MeshMixer …

Femoroacetabular Impingement: Saving The Joint, Ronald Huang, Javad Parvizi

Department of Orthopaedic Surgery Faculty Papers

Many factors have been linked to the development of osteoarthritis (OA) of the hip, but often, cases are still considered “idiopathic.” Femoroacetabular impingement (FAI) has been suggested as a possible etiologic factor for the otherwise “idiopathic” cases. It is theorized that the subtle morphologic abnormalities seen at the head-neck junction and acetabulum in FAI may lead to labral tears, chondral damage, and subsequent progression of OA. Prevalence of FAI has been suggested to be as high as 14% in the general population. It often presents in young active patients that subject their hip joint to repetitive micro trauma associated with …

Interesting Case Presentation: Placental Site Trophoblastic Tumor, Nicole Qualtieri, Ms, Pa (Ascp), Andrea Gadue, Mhs, Pa (Ascp)

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Study:

A 26 year-old female (G3P1) had a D&E in March, 2010 for a blighted ovum. The diagnosis on the uterine contents at an outside institution was placental site trophoblastic tumor. No follow up care was obtained. Four months later (July, 2010), the patient presented to her OB-GYN stating that she had missed a period and had a positive home pregnancy test. An ultrasound examination failed to identify a fetus, and the patient was referred to TJUH.

At Jefferson an MRI showed a poorly defined uterine mass that extended into the myometrium. The slides from the original D&E were …