Medicine and Health Sciences Commons^™

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …

Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown

Dr Robert Brown

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a …

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …

Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …

Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …

Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo

Gyongyi Szabo

Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …

An Essential Role For Monocyte Chemoattractant Protein-1 In Alcoholic Liver Injury: Regulation Of Proinflammatory Cytokines And Hepatic Steatosis In Mice, Pranoti Mandrekar, Aditya Ambade, Arlene Lim, Gyongyi Szabo, Donna Catalano

Gyongyi Szabo

The importance of chemokines in alcoholic liver injury has been implicated. The role of the chemokine, monocyte chemoattractant protein-1 (MCP-1), elevated in patients with alcoholic liver disease is not yet understood. Here, we evaluated the pathophysiological significance of MCP-1 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), in alcoholic liver injury. The Leiber-DeCarli diet containing alcohol or isocaloric control diets were fed to wild-type (WT) and MCP-1-deficient knockout (KO) mice for 6 weeks. In vivo and in vitro assays were performed to study the role of MCP-1 in alcoholic liver injury. MCP-1 was increased in Kupffer cells (KCs) as …

Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer

Gyongyi Szabo

The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of …

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …

The Rbans Effort Index: Base Rates In Geriatric Samples, K. Duff, C. Spering, S. O'Bryant, L. Beglinger, D. Moser, J. Bayless, Kennith Culp, J. Mold, R. Adams, J. Scott

Kennith R. Culp

The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer's disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more …

Twelve-Month Mortality Among Delirium Subtypes, S. Decrane, Kennith Culp, B. Wakefield

Kennith R. Culp

This study used data from the Delirium Among the Elderly in Rural Long-Term Care Facilities Study and data from the National Death Index (NDI) to examine mortality among 320 individuals. Individuals were grouped into noncases, subsyndromal cases, hypoactive delirium, hyperactive delirium, and mixed delirium on the basis of scoring using the Confusion Assessment Method (CAM), NEECHAM Scale, Mini-Mental State Examination (MMSE), Clinical Assessment of Confusion-A (CAC-A), and Vigilance A instruments. Risk ratios of mortality using "days of survival" did not reach statistical significance (alpha = .05) for any subgroup. Underlying cause of death (UCD) using International Classification of Disease, 10th …

Sleeplessness, Deborah Schoenfelder, Keela Herr

Deborah P. Schoenfelder

This article identifies and reviews research related to sleeplessness reported by nurses in the literature. The current state of clinical nursing research as it relates to sleep is evaluated, including the content, methodology, and implications for further research. Although the review indicates current interest in sleep by clinical nurse researchers, the number of nursing studies in the literature is limited, especially within specific areas, such as age groups and setting. Also, directions for future nursing research on sleep are recommended.

Caregiving: Concept Analysis And Outcomes, Elizabeth Swanson, Deborah Schoenfelder, Janet Specht, M. Johnson, Meridean Maas, D. Saylor

Deborah P. Schoenfelder

More than ever before, caregiving has become a salient public policy issue. A number of recent and anticipated demographic, economic and social changes have occurred that make it imperative for researchers to critically examine the impact of caregiving on family caregivers' health, behavior, emotions, and social status. Researchers at the University of Iowa College of Nursing are working to classify standardized nursing-sensitive patient outcomes for use in language development, practice, research, and education to evaluate the effectiveness of nursing interventions and clinical nursing services. This article focuses on family caregiving and the analysis of caregiver role performance in both direct …

Acute Confusion/Delirium, S. Sendelbach, P. Guthrie, Deborah Schoenfelder

Deborah P. Schoenfelder

No abstract provided.

An Exercise Program To Improve Fall-Related Outcomes In Elderly Nursing Home Residents, Deborah Schoenfelder, L. Rubenstein

Deborah P. Schoenfelder

This study tested a 3-month ankle-strengthening and walking program designed to improve or maintain the fall-related outcomes of balance, ankle strength, walking speed, risk of falling, fear of falling, and confidence to perform daily activities without falling (falls efficacy) in elderly nursing home residents. Nursing home residents (N = 81) between the ages of 64 and 100 years participated in the study. Two of the fall-related outcomes, balance and fear of falling, were maintained or improved for the exercise group in comparison to the control group.

Evidence-Based Guideline. Individualized Music For Elders With Dementia, L. Gerdner, Deborah Schoenfelder

Deborah P. Schoenfelder

No abstract provided.

Outcome Indicators For Direct And Indirect Caregiving, Deborah Schoenfelder, Elizabeth Swanson, Janet Specht, Meridean Maas, M. Johnson

Deborah P. Schoenfelder

Informal caregiving and outcomes for caregiving are an important part of health care and of particular importance in nursing. The purpose of this research is to report the results of a survey mailed to nursing experts for validation of the outcome labels Caregiver Role Performance: Direct Care and Caregiver Role Performance: Indirect Care and their accompanying indicators. Experts were asked to rate how important the identified indicators were for assessing those two outcomes. In addition, the respondents were asked to what extent nursing interventions influence the achievement of each identified indicator for Caregiver Role Performance: Direct Care and Caregiver Role …

From Risk For Trauma To Unintentional Injury Risk: Falls--A Concept Analysis. Nursing Diagnosis Extension And Classification Research Team, Deborah Schoenfelder, C. Crowell

Deborah P. Schoenfelder

TOPIC: Concept analysis of the nursing diagnosis risk for trauma. PURPOSE: To examine the nursing diagnosis risk for trauma and to specify the risk factors for falling. SOURCES: Research and informational articles on falling, and NANDA Nursing Diagnoses: Definitions and Classification, 1999-2000. CONCLUSIONS: Replace the current nursing diagnosis risk for trauma with the more specific nursing diagnosis unintentional injury risk: falls. The other risks included in risk for trauma (e.g., burns) also will need to be developed.

Simply The Best: Teaching Gerontological Nursing Students To Teach Evidence-Based Practice. Creating Tip Sheets Can Help Achieve The Goal Of Implementing Ebp In Clinical Facilities, Deborah Schoenfelder

Deborah P. Schoenfelder

This article describes a teaching strategy used in an undergraduate gerontological nursing clinical course to familiarize students with evidence-based practice. Students are required to read and summarize an assigned evidence-based practice guideline published by The University of Iowa Gerontological Nursing Interventions Research Center. They then develop a "tip sheet," based on the assigned guideline, to disseminate to health care staff at their practicum sites, which is either a long-term care facility or a hospital-based skilled nursing facility. Nursing students' reactions to the assignment and nursing staff's responses to the tip sheets are discussed.

Evidence-Based Guideline. Wandering, M. Futrell, K. Melillo, R. Remington, Deborah Schoenfelder

Deborah P. Schoenfelder

No abstract provided.

Creative Practicum Leadership Experiences In Rural Settings, Deborah Schoenfelder, J. Valde

Deborah P. Schoenfelder

Rural healthcare systems provide rich learning environments for nursing students, where strong nursing leaders manage care for people with diverse health problems across the lifespan. The authors describe the development, implementation, and evaluation of rural clinical leadership practicum, a prelicensure course that specifically focuses on the application of leadership concepts in small rural healthcare systems.

The Independent Nurse Role In Community Care Gerontological Nursing, Deborah Schoenfelder, Janet Specht, Meridean Maas

Deborah P. Schoenfelder

No abstract provided.

A Fall Prevention Educational Program For Community Dwelling Seniors, Deborah Schoenfelder, K. Van Why

Deborah P. Schoenfelder

The purpose of this research was to assess participants' responses to a fall prevention educational program. Fourteen persons volunteered to participate in the study conducted at a large senior center. Descriptive statistics were used to characterize the sample and to assess subjects' awareness about falls, attitudes about fall risk, fall prevention behaviors, and incidence of falls before the fall prevention program and again at one month and three months after the program. Forty-six percent of the sample had fallen in the previous year. In general, subjects' perceptions that their risk of falling was lower than others of the same age …

Homesafe: Supportive Assistance For Elderly Individuals Through A Nurse-Managed Plan, Deborah Schoenfelder, Meridean Maas, Janet Specht

Deborah P. Schoenfelder

A lack of quality, cost-effective alternatives to nursing home care for community-dwelling older adults exists. The evidence suggests that case management provides quality care in a cost-efficient manner to help older adults remain at home safely and as independently as possible. This article describes HomeSafe, a nurse-managed membership plan that assists older individuals to enhance their health and quality of life, and to age in place in their homes and communities. HomeSafe serves as an innovative model of care and a teaching site for undergraduate and graduate nursing students and nursing faculty at The University of Iowa.

Work Restrictions: Documenting A Patient's Return To Work, Kerri Rupe

Kerri A. Rupe

Patients frequently ask NPs to write work restrictions, even if it is not in their best interest. This article helps providers construct valid work restrictions and addresses specific tasks and issues to keep the patient and coworkers safe when returning to work.

Assigning Surgical Cases With Regional Anesthetic Blocks To Anesthetists And Operating Rooms Based On Operating Room Efficiency, Cormac O'Sullivan, F. Dexter

Cormac T. O'Sullivan

The popularity of regional anesthesia blocks for both intraoperative anesthesia and postoperative pain management supports the inclusion of the administration of regional anesthesia into discussions about operating room (OR) efficiency. This article reviews the literature on OR efficiency with a focus on day-of-surgery decision making. Vignettes show regional anesthesia block placement is a variable that can affect the efficiency of use of OR time. Clinical examples highlight OR management issues and staff assignment decisions on the day of surgery. Regional anesthetic block placement can affect surgical schedules, and thus OR efficiency. When patient safety is unaffected, rearranging OR schedules on …

Economics And The Education Of Nurse Anesthetists: Part 1, Cormac O'Sullivan, E. Thompson

Cormac T. O'Sullivan

No abstract provided.

Economics And The Education Of Nurse Anesthetists: Part 2, Cormac O'Sullivan, E. Thompson

Cormac T. O'Sullivan

Economic assumptions and other factors affecting the economics of nurse anesthesia education are presented in Part 2 of this 2-part column. In Part 1, published in the October 2004 issue of the AANA Journal, general economic principles and healthcare economic principles in particular were described, explained, and related to the current US healthcare system.