Digital Commons Network^™

Feasibility Of Pulsed Proton Induced Acoustics For 3d Dosimetry, Fahed M. Alsanea

Open Access Theses

Proton therapy has the potential to deposit its energy in tissue with high conformity to the tumor and significantly reduced integral dose to normal tissue compared to conventional radiation, such as x-rays. As a result, local control can be enhanced while reducing side-effects and secondary cancers. This is due to the way charged Particles deposit their energy or dose, where protons form a Bragg peak and establish a well-defined distal edge as a function of depth (range). To date, the dose delivered to a patient from proton therapy remains uncertain, in particular the positioning of the distal edge of the …

3d Visualization Architecture For Building Applications Leveraging An Existing Validated Toolkit, David A. Polyak

Master's Theses (2009 -)

The diagnostic radiology space and healthcare in general is a slow adopter of new software technologies and patterns. Despite the widespread embrace of mobile technology in recent years, altering the manner in which societies in developed countries live and communicate, diagnostic radiology has not unanimously adopted mobile technology for remote diagnostic review. Desktop applications in the diagnostic radiology space commonly leverage a validated toolkit. Such toolkits not only simplify desktop application development but minimize the scope of application validation. For these reasons, such a toolkit is an important piece of a company’s software portfolio. This thesis investigated an approach for …

Metformin Inhibits Androgen-Induced Igf-Ir Up-Regulation In Prostate Cancer Cells By Disrupting Membrane-Initiated Androgen Signaling., Roberta Malaguarnera, Antonella Sacco, Alaide Morcavallo, Sebastiano Squatrito, Antimo Migliaccio, Andrea Morrione, Marcello Maggiolini, Antonino Belfiore

Department of Urology Faculty Papers

We have previously demonstrated that, in prostate cancer cells, androgens up-regulate IGF-I receptor (IGF-IR) by inducing cAMP-response element-binding protein (CREB) activation and CREB-dependent IGF-IR gene transcription through androgen receptor (AR)-dependent membrane-initiated effects. This IGF-IR up-regulation is not blocked by classical antiandrogens and sensitizes cells to IGF-I-induced biological effects. Metformin exerts complex antitumoral functions in various models and may inhibit CREB activation in hepatocytes. We, therefore, evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation. In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription. CRE activity requires the formation of a CREB-CREB …

Association Of Airborne Aspergillus With Asthma Exacerbation In Southern Pakistan., Ali Bin Sarwar Zubairi, Iqbal Azam Syed, Safia Awan, Afia Zafar, Asifali Imam

Department of Medicine

Background: Exposure to airborne fungi has been related with exacerbation of asthma in adults and children leading to increased outpatient, emergency room visits, and hospitalizations. Hypersensitivity to these airborne fungi may be an important initial predisposing factor in the development and exacerbation of asthma.

Objective: This study was conducted to determine an association between fungal types and spore concentrations with the risk of asthma exacerbation in adults.

Methods: This cross-sectional study was conducted from May 2008 to August 2009 at the Aga Khan University Hospital Karachi, Pakistan. All adult (age≥16 years) patients presenting to the hospital with acute asthma exacerbation …

Current Trends In Undergraduate Medical And Dental Research: A Picture From Pakistan, Waqar Jeelani, Sanaa Masood Aslam, Asrar Elahi

Department of Surgery Docs

Abstract

BACKGROUND:

Initiatives taken over the last few years have led us to the day when most of the medical and dental institutions in the developed countries have established a strong research culture at undergraduate level but the situation is quite the contrary in Pakistan. This study was carried out to investigate the current trends in undergraduate medical and dental research and to highlight the research barriers.

METHODS:

A cross-sectional study was conducted at six medical and dental colleges of Rawalpindi and Islamabad. A structured questionnaire was used to collect data from 300 students. Results were recorded as percentages. Findings …

2014 Massachusetts Family Impact Seminar: A Lot On Our Plate; Chronic Health Threats In Massachusetts, Ira S. Ockene M.D., Christina D. Economos Ph.D, Barbara Goldoftas Ph.D, Denise A. Hines Ph.D., Caitlin Alcorn, Jacqueline A. Daigneault, Jordan R. Daley, Maura A. Flanagan, Carsten-Hendrik Rasche, Heather Rios, Julia Tran, Liam Kelly Fleming

Mosakowski Institute for Public Enterprise

A Lot on Our Plate: Chronic Health Threats in Massachusetts is the fifth Massachusetts Family Impact Seminar, and is designed to emphasize a family perspective in policymaking on issues related to childhood obesity, cardiovascular disease, and type 2 diabetes. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families.

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

USF Tampa Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of "old …

Metabotropic Glutamate Receptor-1 As A Novel Target For The Antiangiogenic Treatment Of Breast Cancer, Cecilia L. Speyer, Ali H. Hachem, Ali A. Assi, Jennifer S. Johnson, John Austin Devries, David H. Gorski

Department of Surgery

Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. In addition to cancer cells, brain endothelial cells express mGluR1. In light of these studies, and because angiogenesis is both a prognostic indicator in cancer correlating with a poorer …

Autoantibodies To Agrin In Myasthenia Gravis Patients, Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wen-Cheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei

Immunology and Microbiology Faculty Research Publications

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. …

Challenging Situations In Family Centered Rounds: Making The Best Out Of Worst Case Scenarios, Priti Bhansali, Kerry Moss, Christiane Corriveau, Geeta Singhal, Robert Kavanagh, Jeffrey Simmons

E-Learning Modules

This resource is a workshop intended for both seasoned and novice health care providers who are interested in becoming prepared for challenging scenarios that may be encountered during FCR. Case scenarios of challenging situations relating to discussing sensitive topics, correcting errors, and teaching learners in front of both parents and patients are presented. Tangible opportunities to role model communication skills, efficiency, and teaching skills for trainees are highlighted. The session will conclude with a question and answer session with a multi-specialty panel to share experiences and strategies for addressing the unexpected during FCR. By the end of the workshop, participants …

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …

The American Epidemic: The U.S. Nursing Shortage And Turnover Problem, Patrick Cox, William K. Willis, Alberto Coustasse

Management Faculty Research

Introduction: Nursing shortages have been on the rise throughout the country which has continued to become a problem due to an aging baby-boomer population causing increased turnover through the United States (U.S.). With this need for nurses expected to rise, determining the root causes of this problem are essential for health care providers as costs continue to grow.

Methods: The methodology for the qualitative study was a literature research review of case studies as well as a semi-structured interview. Five electronic databases were minded. Thirty-six articles were utilized in this study.

Results: Through the use of a conceptual framework the …

Vital Signs, Spring 2014, Boonshoft School Of Medicine

Vital Signs

A sixty page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, a research spotlight, alumni notes, and more.

Developmental Origins Of Cardiovascular Disease, Edwina H. Yeung, Candace Robledo, Nansi S. Boghossian, Cuilin Zhang, Pauline Mendola

School of Medicine Publications

Although cardiovascular disease has traditionally been viewed as a condition of aging individuals, increasing focus has turned to its developmental origins. Since birthweight has been related to cardiovascular disease risk, research into factors such as gravid conditions that affect fetal growth have grown. Associations between maternal diabetes and childhood obesity from sibling studies suggest a causal role but prospective studies of gestational diabetes remain mixed. Preeclampsia and increased offspring blood pressure has been consistently observed but evidence for other cardiovascular outcomes is lacking. While maternal obesity is associated with childhood obesity, causality remains unclear and paternal obesity should be investigated …

Melanoma: Attacking On Many Fronts, Michael A. Thompson

Journal of Patient-Centered Research and Reviews

No abstract provided.

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …

Proteoglycans: Road Signs For Neurite Outgrowth, Justin A. Beller, Diane M. Snow

Spinal Cord and Brain Injury Research Center Faculty Publications

Proteoglycans in the central nervous system play integral roles as "traffic signals" for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and …

Irf8 Suppresses Pathological Cardiac Remodelling By Inhibiting Calcineurin Signalling., Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xin-Liang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li

Department of Emergency Medicine Faculty Papers

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits …

Human Adipose-Derived Stem Cell Transplantation As A Potential Therapy For Collagen Vi-Related Congenital Muscular Dystrophy., Vitali Alexeev, Machiko Arita, Adele Donahue, Paolo Bonaldo, Daniel A. Monti, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness within the first two years of life. Collagen VI-related muscle disorders have recently emerged as one of the most common types of CMD. COL6 CMD is caused by deficiency and/or dysfunction of extracellular matrix (ECM) protein collagen VI. Currently, there is no specific treatment for this disabling and life-threatening disease. The primary cellular targets for collagen VI CMD therapy are fibroblasts in muscle, tendon and skin, as opposed to muscle cells for other types of muscular dystrophies. However, recent advances in …

Prevention Of Arteriovenous Shunt Occlusion Using Microbubble And Ultrasound Mediated Thromboprophylaxis., Shelby Kutty, Juefei Wu, James M. Hammel, Joseph R. Abraham, Jeeva Venkataraman, Ibrahim Abdullah, David A. Danford, Stanley J. Radio, John Lof, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts.

METHODS AND RESULTS: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt …

A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …

Metrics Of The Gynecologic Oncology Literature Focused On Cited Utilization And Costs, Edward J. Pavlik, John Hoff, Dylan Woolum, Yuqing Liang, Christiaan Wijers, Melissa Schwartz, Jason Lefringhouse, Lauren Baldwin

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: The newest findings on literature utilization relevant to gynecologic oncology were published by Thomson Reuters during June 2013 as determinants of journal standing. Our objective was to assess the different metrics reported for relative impact and cost for journals relevant to gynecologic oncology.

METHODS: 55 journals were evaluated for Impact Factor (IF), 5Year IF, Immediacy Index, Cited Half Life, Eigenfactor (EF) Score, Article Influence (AI) scores and subscription costs obtained from publisher information.

RESULTS: CA-A Cancer Journal for Clinicians had the highest IF (101.78) & AI (24.502). The top EF cancer-specific journals were the Journal of Clinical Oncology, Cancer …

Inflammation Enhances Il-2 Driven Differentiation Of Cytolytic Cd4 T Cells, Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing …

A Novel In Vivo Model For Evaluating Functional Restoration Of A Tissue-Engineered Salivary Gland., Swati Pradhan-Bhatt, Daniel A Harrington, Randall L Duncan, Mary C Farach-Carson, Xinqiao Jia, Robert L Witt

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retains progenitor cell markers useful for treatment of radiation-induced xerostomia.

STUDY DESIGN: A three-dimensional (3D) hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models, and cell viability and receptor expression were evaluated.

METHODS: A parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids and in vitro were implanted in the three-fourths resected parotid bed of athymic …

Social Media Guidelines And Best Practices: Recommendations From The Council Of Residency Directors Social Media Task Force., Malford T Pillow, Laura Hopson, Michael Bond, Daniel Cabrera, Leigh Patterson, David Pearson, Harsh P. Sule Md, Felix Ankel, Madonna Fernández-Frackelton, R. Hall, Jason A Kegg, Donald Norris, Katrin Takenaka

Department of Emergency Medicine Faculty Papers

Social media has become a staple of everyday life among over one billion people worldwide. A social networking presence has become a hallmark of vibrant and transparent communications. It has quickly become the preferred method of communication and information sharing. It offers the ability for various entities, especially residency programs, to create an attractive internet presence and "brand" the program. Social media, while having significant potential for communication and knowledge transfer, carries with it legal, ethical, personal, and professional risks. Implementation of a social networking presence must be deliberate, transparent, and optimize potential benefits while minimizing risks. This is especially …

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces cerevisiae expressing …

Galectin-1 In Early Acute Myocardial Infarction, Suhail Al-Salam, Satwat Hashmi

Department of Biological & Biomedical Sciences

Myocardial infarction (MI) is the most serious manifestation of coronary artery disease and the cause of significant mortality and morbidity worldwide. Galectin-1(GAL-1), a divalent 14.5-kDa protein, is present both inside and outside cells, and has both intracellular and extracellular functions. Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor mediating early and late responses to myocardial ischemia. Identification of the pattern of expression of GAL-1 and HIF-1α in the heart during the first 24 hours following acute MI will help in understanding early molecular changes in this event and may provide methods to overcome serious complications. Mouse model of MI …

Update On Ranolazine In The Management Of Angina., J Nicolás Codolosa, Subroto Acharjee, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current in myocytes with anti-ischemic and metabolic properties. It was approved by the US Food and Drug Administration in 2006 for use in patients with CSA. Multiple, randomized, placebo-controlled trials have shown that ranolazine improves functional capacity and decreases anginal episodes in CSA patients, …

Regulation Of The Proapoptotic Functions Of Prostate Apoptosis Response-4 (Par-4) By Casein Kinase 2 In Prostate Cancer Cells, A De Thonel, A Hazoumé, V Kochin, K Isoniemi, G Jego, E Fourmaux, A Hammann, H Mjahed, O Filhol, O Micheau, P Rocchi, V Mezger, J E Eriksson, Vivek M. Rangnekar, C Garrido

Radiation Medicine Faculty Publications

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …