Diseases Commons^™

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Effect Of Passive Heating On Males And Females With Elevated Arterial Stiffness, Forrest Blake Robinson

Graduate Theses and Dissertations

Context: Cardiovascular disease (CVD) is one of the leading causes of mortality in the United States, accounting for about 1 in every 4 deaths annually. Studies have shown that passive heating does have some degree of effect on arterial stiffness, but not much is known about populations with higher stiffness. Objective: To examine the independent effect of core temperature increase during passive heating on arterial stiffness. Methods: Participants visited the lab three times; one familiarization and two experimental trials. The experimental trials consisted of subjects being passively heated in an environment of 40°C / 40% relative humidity (HEAT) or normal …

Clinical And Demographic Variables Associated With Cognitive Deficits, Symptom Severity, And Duration After Concussive Injury In Adolescents: A Retrospective Study, Seema S. Aggarwal

Dissertations and Theses (Open Access)

Background: Concussions in adolescents are a public health concern with the growing popularity of high school sports. Recent legislation mandates that athletes who are suspected of a concussion be cleared to return-to-play by a clinician. More research is needed to develop a concussion predictive model to identify populations at risk for more severe and prolonged symptoms and long-term neurologic deficits.

Aims: The aims of this study were to (1) examine the effect of race and gender on neurocognitive and symptom scores and (2) determine which clinical (e.g., number of concussions, migraine history, learning disabilities/ attention deficit disorders) and demographic factors …

Epidemiological Characteristics Of Clinically-Confirmed Cases Of Chikungunya In Teculutan, Guatemala, Annaly Aldana

Senior Honors Projects

As no vaccine currently exists for the Chikungunya virus (CHKV), mosquito control and efficient public health campaigns are crucial for the prevention of disease propagation. The purpose of this research project is to identify populations particularly at-risk for acquiring Chikungunya, and to explore the role that cultural attitudes may play in impacting mosquito-borne disease. Due to its geographical structure and climate, Guatemala is an ideal territory for the spread of emerging and re-emerging mosquito-borne diseases. This project was developed by collaborating with the public governmental health clinic in the municipal town of Teculután, in the department of Zacapa in Guatemala. …

Diffusion Modeling And Device Development For Peritoneal Membrane Oxygenation, Liana Hatoum

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Acute respiratory distress syndrome (ARDS) is a pulmonary disease that causes hypoxemia and respiratory failure. The mortality rate for ARDS ranges between 27% and 45%. Current treatments including mechanical ventilation and extracorporeal membrane oxygenation (ECMO) are often associated with high risk complications including barotrauma, infection, thrombosis, and hemorrhage. Alternative pulmonary support techniques are needed to improve the survival rate of patients suffering from ARDS. Previous studies introducing pure O₂ gas, perfluorocarbons and red blood cells into the intraperitoneal (IP) cavity have reported no effect or only a mild increase in oxygenation. Here we report peritoneal membrane oxygenation (PMO) using …

Association Of Ecological Factors With Rift Valley Fever Occurrence And Mapping Of Risk Zones In Kenya, Gladys Mosomtai, Magnus Evander, Per Sandström, Clas Ahlm, Rosemary Sang, Osama Ahmed Hassan, Hippolyte Affognon, Tobias Landmann

All Peer-Reviewed Publications

Objective: Rift Valley fever (RVF) is a mosquito-borne infection with great impact on animal and human health. The objectives of this study were to identify ecological factors that explain the risk of RVF outbreaks in eastern and central Kenya and to produce a spatially explicit risk map. Methods: The sensitivity of seven selected ecological variables to RVF occurrence was assessed by generalized linear modelling (GLM). Vegetation seasonality variables (from normalized difference vegetation index (NDVI) data) and 'evapotranspiration' (ET) (metrics) were obtained from 0.25-1 km MODIS satellite data observations; 'livestock density' (N/km2), 'elevation' (m), and 'soil ratio' (fraction of all significant …

Health Behaviors And Their Correlates Among Participants In The Continuing To Confront Copd International Patient Survey, Hana Müllerová, Sarah H. Landis, Zaurbek Aisanov, Kourtney J. Davis, Masakazu Ichinose, David M. Mannino, Joe Maskell, Ana M. Menezes, Thys Van Der Molen, Yeon-Mok Oh, Maggie Tabberer, Meilan K. Han

Preventive Medicine and Environmental Health Faculty Publications

Background and aims: We used data from the Continuing to Confront COPD International Patient Survey to test the hypothesis that patients with COPD who report less engagement with their disease management are also more likely to report greater impact of the disease.

Methods: This was a population-based, cross-sectional survey of 4,343 subjects aged ≥ 40 years from 12 countries, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. The impact of COPD was measured with COPD Assessment Test, modified Medical Research Council Dyspnea Scale, and hospital admissions and emergency department visits for COPD in the prior …

The Emergence Of The Zika, Chikungunya, And Dengue Viruses In Brazil, The Dominican Republic, And Puerto Rico, Nelson Xavier Del Pilar

Honors Scholar Theses

The Zika, Chikungunya, and Dengue viruses are three emerging viral infections of the 21st century. Outbreaks have occurred in twenty countries, including areas of South America, and territories in the Caribbean. These viral diseases are mosquito-borne infections transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. The origins of the diseases, viral morphology, and vector transmission will be described in this review as well as symptoms that humans experience, medical testing procedures, and preventative measures. This study will focus on three locations: Brazil, the Dominican Republic, and Puerto Rico. There are many similarities between the three viruses to emphasize, but …

Virus-Host Co-Evolution: Determining The Origin Of Human Cytomegalovirus Us27 And Us28, Jessica A. Scarborough, Juliet Spencer, John Paul

Creative Activity and Research Day - CARD

G protein-coupled receptors (GPCR) are the largest family of cell surface proteins, found in organisms from yeast to humans. Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skilled at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host’s immune system. One aspect of this co-evolution involves the acquisition of four virally encoded GPCR homologs: US27, US28, UL33 and UL78. In this research, phylogenetic analysis was used to investigate the origins of the US27 and US28 genes, which are adjacent in the viral genome. The results indicate that both US27 and US28 share the …

Torn Between Two Diseases: Changes In Tgfβ Signaling Prevents Diabetes But Promotes Neuropathy, Vasalya Panchumarthi

Creative Activity and Research Day - CARD

Type 1 diabetes (T1D) is an autoimmune disease that affects millions of children and adults worldwide. In this disease, white blood cells (Leukocytes) invade, attack, and destroy the Islets of Langerhans in the pancreas, resulting in increased blood glucose levels. Patients with T1D must use exogenous insulin injections, which can lead to many side effects over the lifespan of the person. Therefore, understanding the pathogenesis of this disease is crucial to develop new treatments for patients. The non-obese diabetic (NOD) mouse is a rodent model of T1D as well as other autoimmune diseases such as Sjogren’s syndrome, where immune cells …

Geodemographic Features Of Human Blastomycosis In Eastern Wisconsin, Megan E. Huber, Dennis J. Baumgardner, Jessica J. F. Kram, Melissa A. Lemke

Journal of Patient-Centered Research and Reviews

Purpose

Blastomycosis is an endemic fungal infection. In rural northern Wisconsin, blastomycosis cases are associated with certain environmental features including close proximity to waterways. Other studies have associated blastomycosis with particular soil chemicals. However, blastomycosis also occurs in urban and suburban regions. We explored the geodemographic associations of blastomycosis cases in the more urban/suburban landscape of eastern Wisconsin.

Methods

We conducted a retrospective study of 193 laboratory-identified blastomycosis cases in a single eastern Wisconsin health system, 2007–2015. Controls were 250 randomly selected cases of community-diagnosed pneumonia from a similar time period. Geographic features of home addresses were explored using Google …

Factors Associated With Initiation Of Antiretroviral Therapy In The Advanced Stages Of Hiv Infection In Six Ethiopian Hiv Clinics, 2012 To 2013, Denis Nash, Olga Tymejczyk, Tsigereda Gadisa, Sarah Gorrell Kulkarni, Susie Hoffman, Muluneh Yigzaw, Batya Elul, Robert H. Remien, Maria Lahuerta, Shalo Daba, Wafaa El Sadr, Zenebe Melaku

Publications and Research

Introduction: Most HIV-positive persons in sub-Saharan Africa initiate antiretroviral therapy (ART) with advanced infection (late ART initiation). Intervening on the drivers of late ART initiation is a critical step towards achieving the full potential of HIV treatment scale-up. This study aimed to identify modifiable factors associated with late ART initiation in Ethiopia.

Methods: From 2012 to 2013, Ethiopian adults (n=1180) were interviewed within two weeks of ART initiation. Interview data were merged with HIV care histories to assess correlates of late ART initiation (CD4+ count <150 cells/mL or World Health Organization Stage IV).

Results: The median CD4 count at enrolment in HIV care was 263 cells/mL (interquartile range …

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.

Epidemiology Crucial To Cracking Elizabethkingia Crisis, Angela Tonozzi

Journal of Patient-Centered Research and Reviews

The author explains the epidemiological methods, tools and personnel required to pinpoint the source of Wisconsin’s 2016 outbreak of Elizabethkingia infections.

Clinical Approach To Nonresponsive Pneumonia In Adults Diagnosed By A Primary Care Clinician: A Retrospective Study, Kiley B. Vander Wyst, Jessica J. F. Kram, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Purpose

Community-acquired pneumonia (CAP) is commonly diagnosed in the primary care setting. Management of nonresponsive pneumonia (NRP), i.e. failure to respond to CAP treatment, is not clearly understood. The purpose of this study was to describe the initial work-up and treatment of CAP in the ambulatory primary care setting and to determine relative proportion of, diagnostic approach to and treatment of NRP.

Methods

We retrospectively studied adult patients diagnosed with CAP within our large, integrated health care system from October 2006 through July 2013. Cases were defined as patients with CAP who worsened after 4 days, or did not improve …

Geographic Distribution Of Maternal Group B Streptococcus Colonization And Infant Death During Birth Hospitalization: Eastern Wisconsin, Jessica J. F. Kram, Dennis J. Baumgardner, Kiley B. Vander Wyst, Melissa A. Lemke

Journal of Patient-Centered Research and Reviews

Purpose

Maternal group B Streptococcus (GBS) can be transmitted from a colonized mother to newborn during vaginal delivery and may or may not contribute to infant death. This study aimed to explore the geographic distribution and risk factors of maternal GBS colonization and infant death during birth hospitalization.

Methods

We retrospectively studied mothers with live birth(s) in a large eastern Wisconsin hospital system from 2007 through 2013. Associations between maternal and neonatal variables, GBS colonization and infant death were examined using chi-squared, Mann-Whitney U and t-tests. Multivariable logistic regression models also were developed.

Results

Study population (N = 99,305) had …

Is 13-Valent Pneumococcal Conjugate Vaccine (Pcv13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (Ppsv23) Superior To Ppsv23 Alone For Reducing Incidence Or Severity Of Pneumonia In Older Adults? A Clin-Iq, Starla Hayward, Lou Ann Thompson, Andrea Mceachern

Journal of Patient-Centered Research and Reviews

Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two …

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …

Post-Herpetic Paresis Of The Lower Extremity: An Unusual Complication Of Shingles, Leah Diane Stalnaker, Lynne J. Goebel, Md

Marshall Journal of Medicine

Herpes zoster, or shingles, is a disease process caused by re-activation of varicella zoster virus in the dorsal root ganglia. Most commonly, it presents with burning pain and a characteristic vesicular rash. However neurologic complications may occur, most often including neuralgia, and less commonly paresis. We present a case of post-herpetic paresis in an 86- year- old female.

A Mir-200c/141-Bmi1 Autoregulatory Loop Regulates Oncogenic Activity Of Bmi1 In Cancer Cells., Mingu Kang, Manjari Dimri, Goberdhan P. Dimri

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are known to function as oncomiRs or tumor suppressors and are important noncoding RNA regulators of oncogenesis. The miR-200c/141 locus on chromosome 12 encodes miR-200c and miR-141, two members of the miR-200 family, which have been shown to function as tumor suppressive miRNAs by targeting multiple oncogenic factors such as polycomb group protein BMI1. Here, we show that BMI1 reciprocally functions as a transcriptional repressor of the miR-200c/141 cluster and that BMI1 inhibitors upregulate expression of miR-200c and miR-141. Our data suggest that BMI1 binds to the miR-200c/141 promoter and regulates it through transcription factor binding motifs E-box …

From Sheepish To Self-Assured In The Fight Against Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Uncertainty And Sensitivity Analysis Of A Rift Valley Fever Model, S. A. Pedro, H. E.Z. Tonnang, S. Abelman

All Peer-Reviewed Publications

Rift Valley fever (RVF) is a vector-borne viral disease with pronounced health and economic impacts on domestic animals and humans in much of sub-Saharan Africa. Using techniques of uncertainty and sensitivity analysis (both local derivatives and sampling-based methods) of a mathematical model for RVF transmission in livestock by two population of mosquitoes (Aedes and Culex). We systematically investigate the relative importance of each model parameter for both disease epidemic and endemic activities. The relationship between vertical transmission and basic reproduction number reveals that during epidemic activities vertical transmission accelerates the course of the outbreak as it increases the size of …

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Detecting Gene-Gene Interactions Using A Permutation-Based Random Forest Method, Jing Li, James D. Malley, Angeline S. Andrew, Margaret R. Karagas, Jason H. Moore

Dartmouth Scholarship

Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions.

Just Living Life: A Focus On What Matters Most In Coping With The Risk Of Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Contraception, Abortion And Assisted Fertility Among Muslim Women A Look At Islamic Culture And Policy In Iran And Afghanistan, Hayley Jacobsen

What All Americans Should Know About Women in the Muslim World

Discourse on women's reproductive rights through the lens of Muslim culture. The use of contraception, assisted fertility and abortion, are analyzed in Iran and Afghanistan. The culture surrounding family planning is detailed through a woman’s community, family, religion and the laws that govern the society they live in, which all influence her decision making in these matters. This piece stands as a cultural analysis of women's agency specifically in Middle Eastern Muslim culture, as it stands as a part of a global women's rights movement.

Inadequate Sensitivity Of Laboratory Risk Indicator To Rule Out Necrotizing Fasciitis In The Emergency Department, Elizabeth Burner, Sean Henderson, Guenevere Burke, Jeffrey Nakashioya, Jerome R. Hoffman

Emergency Medicine Faculty Publications

Introduction: Necrotizing fasciitis (NF) is a life-threatening illness, particularly when surgical debridement is delayed. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was developed to identify patients at higher risk for NF. Despite limited information in this regard, the LRINEC score is often used to "rule out" NF if negative. We describe the sensitivity of the LRINEC score in emergency department (ED) patients for the diagnosis of NF.

Methods: We conducted a chart review of ED patients in whom coding of hospital discharge diagnoses included NF. We employed standard methods to minimize bias. We used laboratory data to …