Digital Commons Network^™

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

Cervical Spine Osteomyelitis After Esophageal Dilation In Patients With A History Of Laryngectomy Or Pharyngectomy And Pharyngeal Irradiation, Richard A. Goldman, Md, Jill N. D'Souza, Md, Adam J. Luginbuhl, Md, Joshua E. Heller, Md, Joseph M. Curry, Md, David M. Cognetti, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Dysphagia is a common sequela of the treatment of head and neck cancer and is frequently managed with esophageal dilation in patients with dysphagia secondary to hypopharyngeal stenosis. Reported complications of esophageal dilation include bleeding, esophageal perforation, and mediastinitis. We examine four cases of cervical spine osteomyelitis presenting as a delayed complication of esophageal dilation for hypopharyngeal stenosis in patients with a history of laryngectomy or pharyngectomy and radiation with or without chemotherapy. The history of head and neck surgery and radiation in these patients further complicates the management of the cervical spine osteomyelitis.

Low Zinc Levels Is Associated With Increased Inflammatory Activity But Not With Atherosclerosis, Arteriosclerosis Or Endothelial Dysfunction Among The Very Elderly, Ehimen Aneni, Khurram Nasir

All Publications

BACKGROUND:

Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall.

METHODS:

Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C-reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated.

RESULTS:

There was no significant …

Infectious Diseases, Bert Chapman

Libraries Faculty and Staff Scholarship and Research

Provides information about the role of infectious diseases in the early years of U.S. History, with particular emphasis on how they impacted injuries sustained in military conflict.

Metabolomics Analysis Identifies Intestinal Microbiota-Derived Biomarkers Of Colonization Resistance In Clindamycin-Treated Mice, Robin L.P. Jump, Myreen Tomas, Abhishek Deshpande, Curtis J. Donskey

Faculty Scholarship

Background: The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment. Methods: To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of …

Impact Of Peak/Mid Luteal Estradiol On Pregnancy Outcome After Intracytoplasmic Sperm Injection, Rehana Rehman, Zahir Hussain, Huma Zahir, Rakhshaan Khan

Department of Biological & Biomedical Sciences

Abstract

Objective: To compare peak to mid estradiol ratio with the probability of successful conception after intracytoplasmic

sperm injection.

Method: The quasi-experimental study was conducted in an infertility clinic at Islamabad from June 2010 till August

2011, and comprised couples subjected to intra-cytoplasmic sperm injection. Down-regulation of ovaries was

followed by calculated stimulation, ovulation induction, oocytes retrieval, intra cytoplasmic sperm injection, in vitro

maturation of embryos and finally blastocysts transfer. Serum estradiol was measured by enzyme-linked

immunosorbent assay on ovulation induction day and the day of embryo transfer. Failure of procedure was detected

by beta human chorionic gonadotropin5-25mIU/ml (Group I; …

Knowledge, Attitude And Perceptions About Tetanus And Rabies Among Family Physicians; Results Of A Survey At A Teaching Hospital In Karachi, Pakistan, Siddiqui Sj, Jehan F, Awan S S, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

To assess the knowledge, attitude and perception among family physicians about tetanus and rabies. Setting: This study was conducted at the International Family Physicians Conference held at the Aga Khan University. Method: It was a cross sectional study of convenient sampling. The participants were asked to fill a pre-tested questionnaire comprising of 26 questions. Both open and close ended questions were included. A total of 111 doctors fulfilling the inclusion criteria filled in the questionnaire.Result: Out of 111 doctors who participated in this study, vast majority were working in the urban area (86.5%). 59.5% had not seen a case of …

Bacteria On Shared Mobile Phones Can Lead To Infections, Roberta Basol, Jean Beckel, Judy Gilsdorf-Gracie, Amy Hilleren-Listerud, Terri Mccaffrey, Sherri Reischl, Pamela Rickbeil, Mary Schimnich, Kirsten Skillings, Mary A. Struffert

Articles

It's now a common practice for hospital-owned mobile phones to be shared among healthcare employees from shift to shift. Despite the benefit of increased, timely communication between caregivers, sharing mobile devices can lead to the spread of healthcare-associated infections (HAIs) if they aren't properly disinfected. The Guidelines for Disinfection and Sterilization in Healthcare Facilities describe "non-critical environmental surfaces" as items that are frequently touched by the hand and may pose a risk of secondary infection transmission.

Gendered Violence, Hiv Acquisition, And Clinical/Behavioral Research, Liz Barr, Michele Peake Andrasik, Claire Rappoport, Jessica Mooney, Annet Davis Vogel, Lisa Rossi, Amina Alio

Journal of Health Disparities Research and Practice

HIV incidence and prevalence rates for US women continue to increase, especially among Black and Latina women. In addition, the link between violence and HIV acquisition has been well documented. However, the interaction between violence, HIV risk, and HIV acquisition remains an under-addressed issue in current clinical and behavioral HIV research designs. Because violence against women plays an important role in HIV acquisition and transmission, it is imperative for clinical research to address violence in trial design and implementation. In this article, we discuss the prevalence of violence in women’s lives; the role violence plays in HIV acquisition; and the …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Refugee Health In Montgomery County: A Retrospective Descriptive Study Of Refugee Health Screening Results From April 2007 - April 2008, Marjan Lyons

Master of Public Health Program Student Publications

Introduction: The top refugee health concerns characteristically are associated with parasitic infections, infectious diseases such as malaria, tuberculosis, and parasites, as well as nutritional deficiencies such as anemia, and malnourishment. Understanding the specific health needs of the refugee population will not only improve the transition of the refugees within the United States healthcare systems, but also improve public health within the community.

Methods: Health records from Public Health - Dayton & Montgomery Country were used to obtain the prevalence of both acute and chronic health conditions within the newly resettled refugee population. There were a total of 193 refugees included …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Who's Your Expert? Use Of An Expert Opinion Survey To Inform Development Of American Psychiatric Association Practice Guidelines., Joel Yager, Robert Kunkle, Laura J. Fochtmann, Sara M. Reid, Robert Plovnick, James E. Nininger, Joel J. Silverman, Michael J. Vergare

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: For many clinical questions in psychiatry, high-quality evidence is lacking. Credible practice guidelines for such questions depend on transparent, reproducible, and valid methods for assessing expert opinion. The objective of this study was to develop and demonstrate the feasibility of a method for assessing expert opinion to aid in the development of practice guidelines by the American Psychiatric Association (APA).

METHODS: A "snowball" process initially soliciting nominees from three sets of professional leaders was used to identify experts on a guideline topic (psychiatric evaluation). In a Web-based survey, the experts were asked to rate their level of agreement that …

Cystic Echinococcoses In Mongolia: Molecular Identification, Serology And Risk Factors, Akira Ito, Temuulen Dorjsuren, Anu Davaasuren, Tetsuya Yanagida, Yasuhito Sako, Kazuhiro Nakaya, Minoru Nakao, Oyun-Erdene Bat-Ochir, Tsendjav Ayushkhuu, Narantuya Bazarragchaa, Nyamkhuu Gonchigsengee, Tiaoying Li, Gurbadam Agvaandaram, Abmed Davaajav, Chinchuluun Boldbaatar, Gantigmaa Chuluunbaatar

Harold W. Manter Laboratory of Parasitology: Library Materials

Abstract

Background

Cystic echinococcosis (CE) is a globally distributed cestode zoonosis that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.) is the major causative agent of CE worldwide, recent molecular epidemiological studies have revealed that E. canadensis is common in countries where camels are present. One such country is Mongolia.

Methodology/Principal Findings

Forty-three human hepatic CE cases that were confirmed histopathologically at the National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by analysis of mitochondrial cox1 gene as being caused by either E. canadensis (n = 31, 72.1%) or E. granulosus s.s. ( …

Drug Resistant Tuberculosis: Challenges Of Urbanization, Rumina Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Household Malaria Knowledge And Its Association With Bednet Ownership In Settings Without Large–Scale Distribution Programs: Evidence From Rural Madagascar, Paul J. Krezanoski, Alexander C. Tsai, Davidson H. Hamer, Alison B. Comfort, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background Insecticide–treated bednets are effective at preventing malaria. This study focuses on household–level factors that are associated with bednet ownership in a rural area of Madagascar which had not been a recipient of large–scale ITN distribution.

Methods Data were gathered on individual and household characteristics, malaria knowledge, household assets and bednet ownership. Principal components analysis was used to construct both a wealth index based on household assets and a malaria knowledge index based on responses to questions about malaria. Bivariate and multivariate regressions were used to determine predictors of household bednet ownership and malaria knowledge.

Results Forty–seven of 560 households …

Prevalence, Determinants, And Management Of Chronic Kidney Disease In Karachi, Pakistan - A Community Based Cross-Sectional Study., Saleem Jessani, Rasool Bux, Tazeen Jafar

Community Health Sciences

BACKGROUND:

Chronic kidney disease (CKD) is increasing being recognized as a global public health problem. However, there is dearth of information on the prevalence, determinants, and management of CKD from low- and middle-income countries. The objectives of the study were to determine the 1) prevalence of CKD; 2) socio-demographic and clinical factors associated with CKD; and 3) the existing management of these patients with regards to blood pressure control, and use of antihypertensive medications.

METHODS:

We conducted a cross-sectional study on 2873 participants aged ≥ 40 years in 12 representative communities in Karachi, Pakistan. The primary outcome was clinically significant …

Partially-Latent Class Models (Plcm) For Case-Control Studies Of Childhood Pneumonia Etiology, Zhenke Wu, Maria Deloria-Knoll, Laura L. Hammitt, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In population studies on the etiology of disease, one goal is the estimation of the fraction of cases attributable to each of several causes. For example, pneumonia is a clinical diagnosis of lung infection that may be caused by viral, bacterial, fungal, or other pathogens. The study of pneumonia etiology is challenging because directly sampling from the lung to identify the etiologic pathogen is not standard clinical practice in most settings. Instead, measurements from multiple peripheral specimens are made. This paper considers the problem of estimating the population etiology distribution and the individual etiology probabilities. We formulate the scientific …

Clinical Management Of Skin And Soft Tissue Infections In The U.S. Emergency Departments, Rakesh Mistry, Daniel J. Shapiro, Monika Goyal, Theoklis Zaoutis, Jeffrey Gerber, Catherine Liu, Adam L. Hersh

Emergency Medicine Faculty Publications

Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has emerged as the most common cause of skin and soft-tissue infections (SSTI) in the United States. A nearly three-fold increase in SSTI visit rates had been documented in the nation's emergency departments (ED). The objective of this study was to determine characteristics associated with ED performance of incision and drainage (I+D) and use of adjuvant antibiotics in the management of skin and soft tissue infections (SSTI).

METHODS:

Cross-sectional study of the National Hospital Ambulatory Medical Care Survey, a nationally representative database of ED visits from 2007-09. Demographics, rates of I+D, and adjuvant antibiotic …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Pharmacokinetics And Pharmacodynamics Of Antifungals In Children And Their Clinical Implications, Chris Stockmann, Jonathan E. Constance, Jessica K. Roberts, Jared Olson, Elizabeth H. Doby, Krow Ampofo, Justin Stiers, Michael G. Spigarelli, Catherine Mt Sherwin

Pediatrics Faculty Publications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Myocarditis Complicating Plasmodium Vivax Malaria., Noreen Nasir, Saima Lalani, Zahra Aziz Samani, Aysha Almas

Department of Medicine

Myocarditis complicating Plasmodium vivax malaria is an extremely rare complication. We report this development in a young girl who was diagnosed to have P. vivax malaria on the basis of peripheral smear. While undergoing antimalarial treatment, she developed respiratory distress requiring invasive mechanical ventilation and inotropic support due to cardiogenic shock secondary to myocarditis. Cardiovascular complications are well recognized with Plasmodium falciparum malaria. Nevertheless, a high index of suspicion should be maintained for the same in Plasmodium vivax infection especially if symptoms of heart failure develop in a young patient.

Knowledge, Attitude And Practices Regarding Hiv/Aids Among Adult Fishermen In Coastal Areas Of Karachi., Mubashir Zafar, Nighat Nisar, Masood Kadir, Zafar Fatmi, Zeeshan Ahmed, Kashif Shafique

Community Health Sciences

BACKGROUND:

Migrant populations are at high risk of Human Immuno Deficiency Virus infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS). Studies of HIV/AIDS knowledge, attitudes and practices among fishermen in developing countries have shown gaps in knowledge and fear of contagion with ambivalent attitudes towards HIV/AIDS and inconsistent universal precautions adherence. The aim of this study was to determine the knowledge, attitude and practices regarding HIV/AIDS among adult fishermen in a coastal area of Karachi, Pakistan.

METHODS:

Community based cross sectional study was conducted among fishermen in coastal area of Karachi from June to September 2012. A total of 297 adult …

Cushing’S Storm Secondary To Ectopic Acth Secreting Metastatic Breast Cancer, Maura Bucciarelli Do, Ya-Yu Lee Md, Vasudev G. Magaji Md, Ms

Department of Medicine

No abstract provided.

Performance Of The Oraquick Hcv Rapid Antibody Test For Screening Exposed Patients In A Hepatitis C Outbreak Investigation, Fengxiang Gao, Elizabeth A. Talbot, Carol H. Loring, Jill J. Power, Jodie Dionne-Odom

Dartmouth Scholarship

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

The End Of Alzheimer's Disease - From Biochemical Pharmacology To Ecopsychosociology: A Personal Perspective, Peter J. Whitehouse

Faculty Scholarship

The future of the Alzheimer's disease (AD) field involves a more complete understanding not only the state of current scientific approaches, but also the linguistic and cultural context of preclinical and clinical research and policy activities. The challenges surrounding dementia are large and growing but are only part of broader social and health concerns. In this latter context, the current state of research in the AD area is reviewed together with necessary priorities in moving forward. Creating a more optimistic future will depend less on genetic and reductionist approaches and more on environmental and intergenerative approaches that will aid in …

Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels Do, Katie Mastoris Do, Mark Knouse Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.