Medicine and Health Sciences Commons^™

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …

A Primer For The Student Joining The General Thoracic Surgery Service Tomorrow: Primer 2 Of 7., Colin C. Yost, Rohun Bhagat, David Blitzer, Clauden Louis, Jason Han, Fatima G Wilder, Robert A Meguid

Student Papers, Posters & Projects

This medical student primer discusses general thoracic surgery, which involves treating pathologies involving all structures in the thorax except the heart, thoracic aorta, great vessels, and spine.

Chronicles Of Hbv And The Road To Hbv Cure, Rukaiya Bashir Hamidu, Richard R. Hann, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to …

Variation In How Cognitive Control Modulates Sentence Processing, Abhijeet Patra, Jeremy Kirkwood, Erica L. Middleton, Malathi Thothathiri

Moss-Magee Rehabilitation Papers

Prior research suggests that cognitive control can assist the comprehension of sentences that create conflict between interpretations, at least under some circumstances. However, the mixed pattern of results suggests that cognitive control may not always be necessary for accurate comprehension. We tested whether cognitive control recruitment for language processing is systematically variable, depending on the type of sentential ambiguity or conflict, individual differences in cognitive control, and task demands. Participants completed two sessions in a web-based experiment. The first session tested conflict modulation using interleaved Stroop and sentence comprehension trials. Critical sentences contained syntax-semantics or phrase-attachment conflict. In the second …

Kruppel-Like Factor 8 Regulates Triple Negative Breast Cancer Stem Cell-Like Activity, Giang Le Minh, Emily M Esquea, Tejsi T Dhameliya, Jessica Merzy, Mi-Hye Lee, Lauren E Ball, Mauricio J Reginato

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Breast tumor development is regulated by a sub-population of breast cancer cells, termed cancer stem-like cells (CSC), which are capable of self-renewing and differentiating, and are involved in promoting breast cancer invasion, metastasis, drug resistance and relapse. CSCs are highly adaptable, capable of reprogramming their own metabolism and signaling activity in response to stimuli within the tumor microenvironment. Recently, the nutrient sensor O-GlcNAc transferase (OGT) and O-GlcNAcylation was shown to be enriched in CSC populations, where it promotes the stemness and tumorigenesis of breast cancer cells in vitro and in vivo. This enrichment was associated with upregulation of the …

Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody

Department of Surgery Faculty Papers

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of …

Effect Of Phacoemulsification On Intraocular Pressure In Eyes With Functioning Tube Shunts, Wesam Shamseldin Shalaby, Sonali Patel, Sophia Lam, Allen Ganjei, Aakriti Garg Shukla, Natasha Kolomeyer, Daniel Lee, L. Jay Katz, Marlene Moster, Jonathan Myers, Reza Razeghinejad

Wills Eye Hospital Papers

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts.

Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP > 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP >18 and >15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed.

Results: Twenty-seven eyes of 27 patients with moderate or …

The Extent Of Disability Education In Three Levels Of Nursing Education: A Descriptive Quantitative Stud, Ksenia Zukowsky, Phd, Crnp, Nnp, Julia Ward, Rn, Phd, Ruth Wittmann-Price, Phd, Rn, Anef, Faan

College of Nursing Posters

Purpose

• This quasi-experimental research project, completed by a Qualtrics survey, assessed the knowledge and confidence of baccalaureate, masters, and Doctor of Nursing Practice (DNP) nursing students’ about caring for People With Disabilities (PWD).
• Participants completed a Qualtrics survey to assessed the knowledge and confidence about caring for People With Disabilities.

Incidence And Risk Factors For Retinal Detachment And Retinal Tear After Cataract Surgery: Iris® Registry (Intelligent Research In Sight) Analysis, Michael J. Morano, M. Ali Khan, Qiang Zhang, Colleen P. Halfpenny, Douglas M. Wisner, James Sharpe, Alexander Li, Maurizio Tomaiuolo, Julia A A. Haller, Leslie Hyman, Allen C. Ho

Wills Eye Hospital Papers

Objective To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

Design Retrospective cohort study.

Participants Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017.

Methods Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery.

Main Outcome Measures Incidence and risk factors for RRD or RT within 1 year of cataract surgery.

Results Of the 3 177 195 …

Pimt Is A Novel And Potent Suppressor Of Endothelial Activation, Chen Zhang, Zhifu Guo, Wennan Liu, Kyosuke Kazama, Louis Hu, Xiaobo Sun, Lu Wang, Hyoungjoo Lee, Lin Lu, Xiao-Feng Yang, Ross Summer, Jianxin Sun

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction …

Lysosomal Lipid Peroxidation Regulates Tumor Immunity, Monika Bhardwaj, Jennifer J Lee, Amanda M Versace, Sandra L Harper, Aaron R Goldman, Mary Ann S Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D Winkler, Qin Liu, David W Speicher, Ravi K Amaravadi

Department of Surgery Faculty Papers

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport …

Increasing Covid-19 Vaccination Coverage For Newcomer Communities: The Importance Of Disaggregation By Language, Abigail Steiner, Kristine Knuti Rodrigues, Nadège Mudenge, Janine Young, Rasulo Rasulo, Colleen Payton, Malini Desilva, Jeremy Michel, Mary Fabio, Katherine Yun

College of Population Health Faculty Papers

The COVID-19 pandemic has disproportionately affected refugee, immigrant, and migrant populations. Vaccines are essential for decreasing transmission and severity of COVID-19 infection. Understanding differences in vaccination coverage based on preferred language is crucial for focusing efforts to decrease COVID-19-related disparities. Four sites in the Minnesota Center of Excellence in Newcomer Health collaboratively evaluated completion of primary COVID-19 vaccination series on or before December 31, 2021, for patients who were 12 years or older on June 30, 2021, by preferred language. The non-English/non-Spanish speaking population included 46,714 patients who spoke 174 languages; COVID-19 vaccination coverage by language ranged from 26.2% to …

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer

Department of Orthopaedic Surgery Faculty Papers

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does …

The Role Of Klotho And Fgf23 In Cardiovascular Outcomes Of Diabetic Patients With Chronic Limb Threatening Ischemia: A Prospective Study, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Antonio Gasbarrini, Massimo Massetti, Andrea Flex

Department of Surgery Faculty Papers

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population …

Review Of Cardiovascular Risk Of Androgen Deprivation Therapy And The Influence Of Race In Men With Prostate Cancer, James Fradin, Felix J. Kim, Grace Lu-Yao, Eugene Storozynsky, William K. Kelly

Department of Medical Oncology Faculty Papers

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen …

Current Barriers To Eye Care, Annika Samuelson, Bs

inSIGHT

Barriers to care penetrate all aspects within our healthcare system and ophthalmology is no exception. The World Health Organization (WHO) estimates 2.2 billion people worldwide have vision impairment, half of which are due to preventable causes and/or remain untreated. In the United States, 6 million people are reported to have visual impairment and over one million people are blind.² The leading causes of blindness within the United States are macular degeneration, cataract, glaucoma, and diabetic retinopathy.³ Management of these diseases require access to early detection, therapeutic intervention, and follow up care at regular intervals; for example, nearly half …

Thyroid Eye Disease: Overview And Treatment, Michelle Omega, Ms

inSIGHT

Your immune system consists of a guided molecular army of antibodies equipped to recognize millions of foreign enemy antigens. However, in autoimmune conditions, antibodies are produced which target the cells of your own body. This is how many autoimmune diseases begin, including thyroid eye disease.

Ophthalminute Highlight: A Look Into The Popular, Educational One-Minute Videos, Anza Rizvi, Bs

inSIGHT

Ophthalminute is a series of one-minute videos designed to provide information on different, essential topics in ophthalmology. What separates the Ophthalminute videos from many of the other videos currently available is their unique ability to effectively and succinctly present information into a one-minute video to help viewers learn and better understand the fundamentals of ophthalmology. The videos showcase witty banter, enthusiastic energy, and stimulating visuals. Across YouTube, Twitter, and Instagram, Ophthalminute has received an astonishing over 2000 followers or subscribers and over 20,000 views!

Room To Wiggle, Holden Caplan, Bs

inSIGHT

Uveitis – inflammation of the inside of the eye and the fifth leading cause of vision loss in the USA. Uveitis (of which there are 30-40 types) may be infectious or non-infectious, unilateral or bilateral, of sudden onset or progressing over months to years, and present in any age group. Different etiologies cause different presentations, including both onset and location (front, middle, or back; Table 1) in the eye.

Exploring The Debate: Dmek And Dsek In Corneal Transplantation, Christian Raimondo, Bs

inSIGHT

Scientific progress is rarely a linear process. This notion is especially true as it pertains to the development of surgical techniques that have the potential to shape future clinical landscapes. Corneal transplantation is no exception. From the very first iterations of full corneal transplants performed in the 19th century to the highly nuanced endothelial procedures available today, corneal medicine has served — and continues to foster — an academic arena where research discoveries and surgical innovations come together to advance the field.

Review Of Surgical Management For Closed-Angle Glaucoma, Scott Kozarsky, Ba

inSIGHT

Closed-angle glaucoma, also known as angle-closure glaucoma, is one of the major types of glaucoma. Glaucoma is a term used to describe a broad group of ocular diseases that damage the optic nerve. The type of angle closure with which the patient presents, whether acute, subacute, or chronic, will dictate their treatment. Management of these three presentations will be discussed at length later in this article. In the United States, closed-angle glaucoma is less common than open-angle glaucoma, which often has a gradual onset of intraocular pressure (IOP) elevation and optic nerve damage.

Age-Related Macular Degeneration And Emerging Treatments – With Advice From Dr. Ajay Kuriyan On Balancing Research With Clinical Responsibilities, Charles Deyoung, Ba

inSIGHT

Age-related macular degeneration (AMD) is a chronic disease of the central retina and a leading cause of vision loss worldwide. Although the early stages of AMD may present asymptomatically, the disease may progress and lead to severe visual impairment via geographic atrophy (“late dry”) or neovascular (“wet”) AMD. In geographic atrophy (GA), there is progressive atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and photoreceptors due to lipofuscin (Drusen) accumulation between the RPE and Bruch’s membrane.¹ These Drusen deposits grow and create an inflammatory and metabolically dysfunctional environment for the photoreceptors supplying the macula (Figure 1).² Eventually, the …

Insight, Volume 3, Issue 1, 2023

inSIGHT

Contents

8 - Age-Related Macular Degeneration and Emerging Treatments
By Charles F. DeYoung

13 - Review of Surgical Management for Closed-Angle Glaucoma
By Scott C. Kozarsky

18 - Exploring the Debate: DMEK and DSEK in Corneal Transplantation
By Christian Raimondo

23 - Room to Wiggle
By Holden Caplan

30 - Ophthalminute Highlight
By Anza Rizvi

34 - Thyroid Eye Disease: Overview and Treatment
By Michelle Omega

38 - Current Barriers to Eye Care
By Annika G. Samuelson

Seeing Eye To Eye: An Overview Of Strabismus And Approach To Treatment, Shreya Swaminathan, Bs

inSIGHT

Strabismus is a heterogenous group of conditions characterized by the misalignment of the eyes. It may manifest as constant or intermittent deviation, meaning the eyes sometimes appear well aligned, or straight, and sometimes appear misaligned. Vision can be normal in some patients, but when associated with amblyopia, may be decreased vision in one eye. There is sometimes diminished binocular vision, with decreased depth perception.

A Look Into Oculoplastics: Repairing Lower Eyelid Defects From Carcinomas, Cameron Haghshenas, Bs

inSIGHT

Eyelids are the thinnest, most sensitive skin we have and can easily be damaged by sun exposure. This is evident given that 5 - 10% of all skin cancers occur on the eyelid, and over half of these occur on the lower eyelid¹. Most of such cases are basal cell carcinomas, which are slow-growing cancers that arise from the basal cell layer, the deepest part of the epidermis. If left untreated or improperly treated, these tumors can extend into adjacent tissues and bone, or recur. Squamous cell carcinomas can also occur on the lower eyelid, although they represent …

Manual Small-Incision Cataract Surgery, Ankur Nahar, Bs

inSIGHT

Of the 49 million people living with blindness worldwide, 15.2 million are blind due to cataracts, making it the leading cause of preventable blindness.^1,2 Furthermore, 65.2 million people experience moderate to severe vision impairment from cataracts, according to the World Report on Vision published by the World Health Organization (WHO).³ While global cataract surgery efforts have been a major success over the past three decades, an aging population has resulted in a rapid rise in cataracts, primarily in low- and middle-income countries (LMICs).^2,4 To address the increasing demand for cataract treatment, countries must perform an equal or …

Gatt: A Micro-Invasive Glaucoma Surgery And A Big Step For Glaucoma Treatment, Mose Im, Bs

inSIGHT

Glaucoma is a group of ocular diseases characterized by damage to the optic nerve that may lead to permanent vision loss. Currently, 76 million people (aged 40-80 years) suffer from glaucoma, and the prevalence is projected to increase to 111.8 million by 2040.¹ The diagnosis of glaucoma can be frightening, particularly because there is no known cure. Fortunately, recent advancements in glaucoma surgery have made more options available for patients presenting with new-onset glaucoma. In particular, patients with mild to moderate glaucoma may be eligible for newer minimally invasive glaucoma surgeries (MIGS). This review is both an overview of …

Origins Of The Wills Eye Manual: Surviving The Test Of Time, Jordan Safran, Bs

inSIGHT

The first copy of the Wills Eye Manual hit the press in late 1989; it featured a black cover page with bold gold lettering and the Wills Eye logo proudly displayed on top. Published in a time before the invention of the world wide web or the advent of digital printing, this 450-page expertly sourced ocular disease reference guide took the ophthalmology world by storm. Since its debut, the manual has served as the go-to guide for trainees and seasoned physicians alike in diagnosing and treating more than 200 ocular diseases. To date, the Wills Eye Manual has published eight …

A Day In The Life In The Wills Er, Samara Hamou, Ms1

inSIGHT

The Wills Eye Hospital — among the greatest eye hospitals in the country — is a force to be reckoned with. Located in Center City Philadelphia, the eight-story tall brick facility will capture your attention as you stroll down Walnut Street. The entrance to the Wills Eye Emergency Room (ER), however, is less apparent to the average city-goer. Located directly across from the Hospital, the red and blue entrance sign may go unnoticed to the unsuspecting by passer. However, for those who require expert eye care in a timely fashion, the Eye Emergency Room is a signal for the invaluable …

Neuro-Ophthalmology Subspecialty Highlight: With Dr. Sarah Thornton, Wills Eye Hospital, Joseph D. Desimone, Bs

inSIGHT

Neuro-Ophthalmology is a subspecialty within ophthalmology that combines the complexities of nervous system disease with the intricacies of the ocular manifestations of those diseases. Neuro-ophthalmologists work closely with neurologists, neurosurgeons, rheumatologists, and other ophthalmologists in different subspecialties, such as retina and glaucoma, to get to the source of their patients’ problems. Neuro-ophthalmology is typically a 1-year fellowship undertaken after residency training is completed, where physicians will learn the complex ways different diseases can manifest in the eye.