Medicine and Health Sciences Commons^™

Reduction Of Endothelial Nitric Oxide Increases The Adhesiveness Of Constitutive Endothelial Membrane Icam-1 Through Src-Mediated Phosphorylation, Feng Gao, Brandon P. Lucke-Wold, Xiang Li, Aric F. Logsdon, Li-Chong Xu, Sulei Xu, Kyle B. Lapenna, Huaqi Wang, M.A. Hassan Talukder, Christopher A. Siedlecki, Jason D. Huber, Charles L. Rosen, Pingnian He

Faculty & Staff Scholarship

Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10–30min. This quick response occurred in the absence of alterations of adhesion molecules on leukocytes and also opposes the classical pattern of ICAM-1-mediated leukocyte adhesion that requires protein synthesis and occurs hours after stimulation. The objective …

Relationship Of Transmural Variations In Myofiber Contractility To Left Ventricular Ejection Fraction: Implications For Modeling Heart Failure Phenotype With Preserved Ejection Fraction, Yanghoub Dabiri, Kevin L. Sack, Semion Shaul, Partho P. Sengupta, Julius M. Guccione

Faculty & Staff Scholarship

The pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocardial dysfunction and compensatory increased subepicardial contractility may underlie preservation of LVEF in patients with HFpEF. We quantified alterations in myocardial function in a mathematical model of the human LV that is based on the finite element method. The fiber-reinforced material formulation of the myocardium included passive and active properties. The passive material properties were determined such that the diastolic pressure-volume behavior of the LV …

Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li

Faculty & Staff Scholarship

Quantum confined materials have been extensively studied for photoluminescent applica- tions. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio- imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Mucinous Adenocarcinoma Of The Scalp: Primary Cutaneous Neoplasm Versus Underlying Metastatic Disease, Ciara A. Brown, Michael C. Lynch, Cristiane M. Ueno

Faculty & Staff Scholarship

Primary cutaneous mucinous carcinoma (PCMC) is a rare mucin-pro- ducing malignancy derived from epithelial glandular structures. The literature re- garding this topic is mostly in the form of case reports and case series. PCMC tends to present in the elderly with predilection for the head and neck and on initial assessment it can be easily mistaken for a simple inclusion cyst. Although PCMC is often indolent in nature, in rare instances it can metastasize and should remain a differential diagnosis in a selected population. The significance in identifying PCMC is reliably differentiating it from metastatic mucinous adenocarcinoma. We present a …

Isolated Inferior Rectus Muscle Entrapment Following Endoscopic Sinus Surgery, Scott Shapiro, Jamie L. Schaefer, Sumeet Gupta, John Nguyen, Brian Kellerymeyer

Faculty & Staff Scholarship

Orbital complications are known risks of endoscopic sinus surgery (ESS). The lamina papyracea and medial rectus muscle are the most commonly injured structures during ESS. Inferior rectus injury is more rare, with only one reported case of isolated inferior rectus injury in the literature. Guidelines for managing ESS-induced inferior rectus injury do not exist, and delayed intervention and management of adjacent sinuses may affect long-term outcomes such as persistent diplopia and disfigurement. In this report, we present a case of a 67-year-old man with diplopia due to isolated left inferior rectus muscle entrapment and injury from violation of the orbital …

Pseudomonas Aeruginosa Algr Phosphorylation Status Differentially Regulates Pyocyanin And Pyoverdine Production, Alexander S. Little, Yuta Okkotsu, Alexandria A. Reinhart, Heath Damron, Mariette Barbier, Brandon Barrett, Amanda G. Ogledby-Sherrouse, Joanna B. Goldberg, William L. Cody, Michael J. Schurr, Michael L. Vasil

Faculty & Staff Scholarship

Pseudomonas aeruginosa employs numerous, complex regulatory ele- ments to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial viru- lence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-type PAO1, that algZR and hemCD are cotranscribed and show differential iron-dependent gene expression. Previous ex- pression profiling was performed in strains without algR and revealed that AlgR acts as either an activator or repressor, depending on the gene. Thus, examination of P. aeruginosa gene expression from cells locked into different AlgR phosphorylation states …

Tracheocutaneous Sinus Following Tracheocutaneous Fistula Repair: Management Strategies In A Pediatric Patient, Adam Bender-Heine, Habib G. Zalzal, Nainika Nanda, Hassan Ramadan

Faculty & Staff Scholarship

Objective. To present a rare case of a pediatric tracheocutaneous sinus years after repair of a tracheocutaneous fistula and to review management strategies. Background. A tracheocutaneous fistula is a common sequela of pediatric tracheostomy and can occur in as many as one in three pediatric patients. There is debate in the literature regarding optimal surgical management. Case Presentation. An 8-year-old girl presented to the emergency department with swelling and erythema over the anterior neck. Clinical exam and diagnostic imaging revealed an underlying tracheocutaneous sinus. Discussion. Complications following pediatric tracheostomy are common and range in complexity from stomal granulation to tracheocutaneous …

Transaortic Gunshot Wound Through Perivisceral Segment Successfully Managed By Placement Of Thoracic Stent Graft, Jared T. Feyko, Peter Zmijewski, Cara Lyle, Allison Wilson, Luke Marone

Faculty & Staff Scholarship

We describe a 36-year-old woman who presented to our facility after sustaining a gunshot wound to the epigastric region. The gunshot resulted in injury to the left lobe of the liver and the twelfth thoracic vertebral body as well as in a through- and-through injury to the abdominal aorta at the level of the celiac axis. The vascular injury was managed successfully by placement of a thoracic stent graft with coverage of the celiac axis. This case demonstrates the feasibility of managing this uncommon injury with endovascular techniques. (J Vasc Surg Cases and Innovative Techniques 2018;4:24-6.)

Hyperspectral Imaging And K-Means Classification For Histologic Evaluation Of Ductal Carcinoma In Situ, Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis

Faculty & Staff Scholarship

Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spec- tral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated …

Macrophage Sensing Of Single- Walled Carbon Nanotubes Via Toll- Like Receptors, Sourav P. Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T. Andon, Tana Brzicova, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Ritta Lahesmaa, Bengt Fadeel

Faculty & Staff Scholarship

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger

inflammation. However, how these materials are ‘sensed’ by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. …

Thoracic Stent Graft Placement For Repair Of Iatrogenic Aortic Injury Secondary To Sheath Placement During Pacemaker Insertion, Jared T. Feyko, Kelsey Musgrove, Cara Lyle, Alexandre D'Audiffret

Faculty & Staff Scholarship

We describe the inadvertent cannulation of the proximal descending thoracic aortic stent with a five French sheath during attempted pacemaker placement in an 88- year-old male. The injury was managed successfully by the percutaneous placement of a thoracic aortic stent graft with good outcome. Our case highlights the feasibility of managing this uncommon injury with this technique.

Palatine Tonsil Stenting Of The Airway As Determined By Drug-Induced Sleep Endoscopy, Habib G. Zalzal, Steven Coutras

Faculty & Staff Scholarship

Objective. To demonstrate lateral pharyngeal wall collapse and increased apnea-hypopnea index in a child posttonsillectomy. Background. Some children have worsening of their sleep symptoms after tonsillectomy for obstructive sleep apnea. This case report demonstrates an open airway on drug-induced sleep endoscopy (DISE) in a child with tonsillar hypertrophy followed by more pronounced airway obstruction related to lateral pharyngeal wall collapse after tonsillectomy. Case Presentation. A 7-year- old boy presented with obstructive sleep apnea and underwent workup with DISE. Following adenotonsillectomy and subsequent lingual tonsillectomy with epiglottopexy, the patient’s sleep apnea symptoms and polysomnogram results worsened. Subsequent DISE showed a more …

Assessment Of A Mouse Xenograft Model Of Primary Colorectal Cancer With Special Reference To Perfluorooctane Sulfonate, Jeffrey H. Wimsatt, Caitlin Montgomery, Laurel S. Thomas, Charity Savard, Rachel Tallman, Kim Innes, Nezar Jrebi

Faculty & Staff Scholarship

Colorectal cancer ranks third among the most commonly diagnosed cancers in the United States. Current therapies have a range of side effects, and the development of a reliable animal model to speed the discovery of safe effective preventative therapies would be of great value. A cross-sectional study in a large Appalachian population recently showed an association between low circulating levels of perfluorooctane sulfonate (PFOS) and a reduced prevalence of colorectal cancer. A study using APCmin(C57BL/6J-ApcMin/J) mice prone to familial adenomatous polyposis found PFOS was protective when exposure occurred during tumor development. To test the possible benefit of PFOS on spontaneous …