Medical Specialties Commons^™

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

Is Laparoscopic Gastric Banding An Effective Treatment For Obesity In Adolescents And Adults As Measured By Physical Function?, Shawna Mccormick

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Is laparoscopic gastric banding an effective treatment for obesity in adolescents and adults as measured by physical functioning?”

STUDY DESIGN: Review of all English language primary studies from 2009, 2010, and 2011.

DATA SOURCES: Two randomized control trials and one cohort study were found using PubMed, Medline, and OVID.

OUTCOMES MEASURED: There were multiple outcomes measured in the studies but the outcome of concern is quality of life post-operatively, specifically, physical functioning as measured by surveys including SF-36, Moorehead-Ardelt, BAROS, and CHQ CF-50. …

Is Administration Of Depot Medroxyprogesterone Acetate Injections Every Three Months Effective In Decreasing Pain Associated With Endometriosis In Premenopausal Women?, Maria Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic EBM review is to determine whether or not the administration of depot medroxyprogesterone acetate injections every three months are effective in decreasing pain associated with endometriosis in premenopausal women.

STUDY DESIGN: A review of two randomized controlled trials and one randomized comparative trial comparing pain improvement from depot medroxyprogesterone acetate (DMPA) injections at different time intervals and/or in comparison to other hormonal birth control methods in premenopausal patients suffering from endometriosis.

DATA SOURCES: Randomized controlled trials and a randomized comparative trial were found using PubMed and Ovid MEDLINE databases.

OUTCOME MEASURED: Outcomes were …

Is Oral Rivaroxaban Safe And Effective In The Treatment Of Patients With Symptomatic Dvt?, Ami A. Patel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not oral rivaroxaban is safe and effective in the treatment of patients with symptomatic DVT.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2007-2011.

DATA SOURCES: Three randomized controlled trials studying the effectiveness and safety of rivaroxaban in the treatment of patients with symptomatic DVT in comparison to enoxaparin and placebo.

OUTCOMES MEASURED: Outcomes measured were episodes of recurrent DVT and bleeding. Patients were monitored for the proposed treatment period and seen at fixed intervals that were matching …

Are Triptan Drugs Safe And Effective For Use In The Prevention Of Menstrually Related Migraines (Mrms)?, Christina Ponzio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Triptan drugs are safe and effective for use in the prevention of menstrually related migraines (MRMs).

STUDY DESIGN: Review of two English language randomized controlled trials and one pilot randomized control trial.

DATA SOURCES: Randomized controlled trials comparing Triptan drugs to a placebo group were found using Medline, PubMed, and OVID.

OUTCOMES MEASURED: Incidence of MRM based on patient self-report; number of relapses; patients’ subjective evaluations of effectiveness based on questionnaire; adverse effects of Triptan treatment.

RESULTS: Two randomized controlled trials …

Is Pramipexole Safe And Effective In Reducing Depressive Symptoms In Patients With Mild To Moderate Parkinson’S Disease And Depression?, Corinne J. Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not pramipexole (Mirapex) is a safe and effective drug to treat depression in patients with mild to moderate Parkinson’s Disease (PD).

STUDY DESIGN: Review of three English language primary randomized controlled trials and one randomized prospective, observational study published between 2003-2010.

DATA SOURCES: Three randomized controlled trials and one randomized prospective, observational study comparing the efficacy of pramipexole to placebo, sertraline (an SSRI) and other dopamine agonists (pergolide) in the treatment of PD related depression symptoms were found using PubMed.

OUTCOME(S) MEASURED: Each of the …

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …

Is Dabigatran Superior To Warfarin In Treating Patients With Atrial Fibrillation?, Kelly Higgins

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Dabigatran is superior to Warfarin in patients with atrial fibrillation.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials found using Cochrane Database.

OUTCOME(S) MEASURED: Outcomes measured were presence or absence of stroke or systolic embolism and intracranial hemorrhage. The absence of these events preserved neurologic function in patients with atrial fibrillation.

RESULTS: In both VKA-naïve and VKA-experienced patients, Dabigatran 150 mg was superior to Warfarin in both the prevention of stroke …

Does Daily Intake Of Glucosamine Supplements Prevent The Need For Knee Replacements Later In Life For Adult Patients Predisposed To Osteoarthritis?, Nancy Helmy

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not daily intake of glucosamine supplements prevents the need for knee replacements later in life for adults predisposed to osteoarthritis.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published between 2001 and 2008

DATA SOURCES: Three double blind randomized control trials comparing glucosamine supplements to placebo were found using PubMed.

OUTCOMES MEASURED: Outcomes were measured using radiographic studies of the knees, joint space measurements, and symptoms were evaluated using Lequesne and WOMAC indexes.

RESULTS: The Reginster (2001) and Pavelka (2002) studies demonstrated no …

Is Fentanyl Pectin Nasal Spray Safe And Effective For Patients With Breakthrough Cancer Pain?, Salina G. Elengical

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether fentanyl pectin nasal spray (FPNS) is safe and effective treatment for patients with breakthrough cancer pain.

STUDY DESIGN: Review of three English language primary randomized controlled trials published 2010-2011.

DATA SOURCES: Multicenter, randomized, double-blind, double-dummy, placebo-controlled trials comparing fentanyl pectin nasal spray, immediate-release morphine sulfate, and/or nasal spray placebo were found using PubMed, COCHRANE, and Medline databases.

OUTCOME MEASURED: All three studies essentially used similar parameters to measure effectiveness and safety of fentanyl pectin nasal spray compared to oral immediate-release morphine sulfate and/or placebo. Baseline pain intensity …

Is Omalizumab A Safe And Effective Treatment For Chronic Urticaria?, Ashley L. Davis

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not omalizumab is a safe and effective treatment for chronic urticaria.

STUDY DESIGN: Review of two randomized controlled studies and one crossover study. All three studies are published in English between 2008-2011.

DATA SOURCES: Two randomized, double blind, placebo controlled studies and one crossover study found using PubMed and EBSCOhost.

OUTCOMES MEASURED: Each trial measured the duration, size, number and/or intensity of wheals. This was done by using the urticaria activity score (UAS). Quality of life was also measured using Dermatology Life Quality Index (DLQI), …

Is Local Infiltration Analgesia (Lia) A Safe And Effective Method For Post-Operative Pain Management After A Unilateral Total Knee Arthroplasty (Tka)?, Brooke A. Bonnette

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not local infiltration analgesia (LIA) is a safe and effective method for post-operative pain management after a unilateral total knee arthroplasty (TKA).
STUDY DESIGN: Review of three English language primary studies published in 2010 and 2011.

DATA SOURCES: Three randomized controlled trials comparing local infiltration analgesia to three separate controls: epidural analgesia, placebo infiltration and femoral nerve block found using PubMed.

OUTCOMES MEASURED: Clinical outcome was measured by total morphine use postoperatively and average knee pain intensity at rest and upon movement postoperatively. Total morphine use …

What Is The Effectiveness Of Onabotulinumtoxina (Botox®) In Reducing The Number Of Chronic Migraines (Cm) In Patients 18-65 Years Old?, Kristin A. Beddingfield

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not onabotulinumtoxinA (Botox®) is effective in reducing the number of chronic migraines (CM) in patients 18-65 years old? Study Design: Review of three published, double blind randomized controlled trials were used for this review, which were found on PubMed; were selected based on their relevance to the clinical question and if they included patient oriented outcomes.

OUTCOMES MEASURED: The outcomes measured were headache/migraine free days measured by >50% responder rate analysis, the Treatment Responder Rate based on Physician Global Assessment, and total adverse events reported by …

Is Phlogenzym Effective In Reducing Moderate To Severe Osteoarthritis Pain In Adults?, Vanessa K. Wood

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Phlogenzym (or ERC) effective in reducing moderate to severe osteoarthritis pain in adults.

STUDY DESIGN: Review of three randomized controlled trials in the English language from 2001 to 2006.

DATA SOURCES: Two double blind RCTs and one open RCT was found using Cochrane Library EBM Online Database, Ovid Medline, and PubMed Online.

OUTCOMES MEASURED: Each of the three studies measured for pain at rest, pain with motion, and restricted function at baseline assessing efficacy using the Lequesne’s Algofunctional Index, visual analog scales, and …

Is Topiramate Effective In Preventing Pediatric Migraines?, Krystina Zeliff

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Topiramate is effective in the prevention of pediatric migraines.
Study Design: Review of three English language randomized control trials published in 2005, 2007, and 2009.

DATA SOURCES: Three double-blind, placebo-controlled, randomized trials comparing various doses of Topiramate to placebo were found using PubMed, OVID, and Cochrane Library databases.

OUTCOME(S) MEASURED: The frequency of migraines in patients under the age of 18 years old was documented with headache diaries. The patient’s parent would record the number, severity, duration, associated symptoms, and use of acute …

Is Transdermal Glyceryl Trinitrate A Safe And Effective Treatment For Primary Dysmenorrhea?, Sarah E. Visich

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective evidence based medicine review is to determine whether or not transdermal glyceryl trinitrate is a safe and effective treatment for primary dysmenorrhea.

STUDY DESIGN: Review of two English language randomized control trials (RCTs) published in 1996 and 1999 and one English language pilot study in 1997.

DATA SOURCES: Two double-blind, randomized, placebo-controlled cross-over studies and one pilot study comparing transdermal glyceryl trinitrate to placebo were found using PubMed, Medline and OVID.

OUTCOME MEASURED: Outcomes measured were based on pain intensity scores (PID) assessed on a visual analog scale and the …

Does Etravirine Decrease Central Nervous System (Cns)/Neuropsychiatric (Nps) Adverse Events Compared To Efavirenz, In Hiv Positive Patients?, Angelo D. T. Smith

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Etravirine (ETR) decreases adverse reactions on the central nervous system (CNS) compared to Efavirenz (EFV) in Human Immunodeficiency Virus (HIV) positive patients.

STUDY DESIGN: Review of three, English language, primary randomized controlled trial studies published in 2011.

DATA SOURCES: Three randomized controlled trials studying the possible decrease of ADR’s in HIV positive patients who are taking Efavirenz compared to study medication Etravirine.

OUTCOME(S) MEASURED: Outcomes measured were by surveys from patients that assess the development or cessation of CNS ADR’s. The self …

In Adults With Acute Diarrhea, Which Treatment Is More Effective Between Loperamide And Racecadotril?, Lorena A. Castillo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine which treatment is more effective between loperamide and racecadotril to treat acute diarrhea in adults.

STUDY DESIGN: Review of three English language primary randomized controlled studies published from 1999-2005.

DATA SOURCES: First study was a RCT that was double blinded, double placebo, parallel study group and second and third study was RCT single blinded, comparative parallel group that all compared efficacy of loperamide and racecadotril. These were all found by using PubMed, COCHRANE and NCBI.

OUTCOMES MEASURED: Each of the studies measured the efficacy of each …

Characterization Of Brer Interaction With The Bile Response Promoters Breab And Brer In Vibrio Cholerae, Francisca A. Cerda-Maira, Gabriela Kovacikova, Brooke A. Jude, Karen Skorupski, Ronald Taylor

Dartmouth Scholarship

The Vibrio cholerae BreR protein is a transcriptional repressor of the breAB efflux system operon, which encodes proteins involved in bile resistance. In a previous study (F. A. Cerda-Maira, C. S. Ringelberg, and R. K. Taylor, J. Bacteriol. 190:7441-7452, 2008), we used gel mobility shift assays to determine that BreR binds at two independent binding sites at the breAB promoter and a single site at its own promoter. Here it is shown, by DNase I footprinting and site-directed mutagenesis, that BreR is able to bind at a distal and a proximal site in the breAB promoter. However, only one of …

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …

A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …

‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult

Nebraska Center for Virology: Faculty Publications

The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …

Recent Advances On The Use Of Structural Biology For The Design Of Novel Envelope Immunogens Of Hiv-1, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine to end the AIDS pandemic, but none has yet succeeded. The lessons learned have repeatedly informed us that the traditional or conventional approaches directly using the pathogens or subunits will not be sufficient for an effective HIV/AIDS vaccine. Recent advances in structure-based technology have shown some promise in the quest for a better immunogen in HIV vaccine development. According to the basic binding structural relationship of an antigen and an antibody, structure-based antigen design could bring some hope for the development of an effective vaccine against …

The Highly Conserved Layer-3 Component Of The Hiv-1 Gp120 Inner Domain Is Critical For Cd4-Required Conformational Transitions, Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, …

Analysis Of Primary Resistance Mutations To Hiv-1 Entry Inhibitors In Therapy Naive Subtype C Hiv-1 Infected Mother– Infant Pairs From Zambia, Hongyan Guo, Chang Liu, Bin Liu, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT.

Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc.

Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were …

Early Childhood Infection Of Kaposi’S Sarcoma-Associated Herpesvirus In Zambian Households: A Molecular Analysis, Landon Olp, Danielle M. Shea, Maxine K. White, Clement Gondwe, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated …

Neurocognitive Function Declines Following Migraine Headache In College Students, Marguerite Moore, T. Covassin, K.A. Pfeiffer, R.E. Norris, R.L. Jensen, C.F. Branta

Journal Articles

No abstract provided.