Digital Commons Network^™

Perception Of Disease Risk And Vulnerability As A Function Of Proximity To National Park Boundaries In East Africa, Irene Bridget Feretti

Honors Theses and Capstones

Studies suggest households closest to parks and protected areas (PAs) are more likely to sustain park-related losses, but the relationship between human sickness and PAs has not been fully explored. Existing literature primarily focuses on human-wildlife conflicts (i.e. crop raiding) and the potential for zoonotic disease spillover and emergence at the human-livestock-wildlife interface at PA boundaries. Understanding local perceptions of disease risk and vulnerability is essential for assessing human health relative to conservation areas. This understanding will promote better-informed consideration of human health impacts in decision making for conservation. Data from surveys taken at 301 households around Kibale National Park …

Cardio-Oncology For The 21st Century: Introduction., Marc L Schwartz, Md

Division of Cardiology Faculty Papers

Based on the latest statistics the prognosis for patients with malignancy has dramatically improved. The overall 5 year survival rate for those who were diagnosed with a cancer between 2002 and 2008 was approximately 65%¹, and as of 2008, 12 million Americans were cancer survivors.² However, this extended longevity now exposes these patients to the risk of other health issues related to their primary cancer or to the treatment that ensured their survival. Specifically, patients who have not succumbed prematurely to their oncologic disease may develop cardiovascular disease that is either a result of the long-term effects …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

Hepatocellular Carcinoma In Native South Asian Pakistani Population; Trends, Clinico-Pathological Characteristics & Differences In Viral Marker Negative & Viral-Hepatocellular Carcinoma, Amna Subhan Butt1, Saeed Hamid, Ashfaq Ahmad Wadalawala, Mariam Ghufran, Ammar Asrar Javed, Omer Farooq, Bilal Ahmed, Tanveer Ul Haq, Wasim Jafri

Section of Gastroenterology

Background

HCC is the fifth most common cancer globally. Our study was conducted to (1)investigate the trends and clinico-pathological characteristics of Hepatocellular carcinoma among native South Asian patients in Pakistan, (2)to estimate the prevalence as well as the trends of viral marker negative HCC and (3) to compare the clinico-pathological, radiological characteristics, applicability of treatment at diagnosis and prognostic factors among patients with both viral marker negative and viral marker positive-HCC being consulted at Aga Khan University Hospital(AKUH), Karachi, Pakistan.

Method

Patients ≥18 years, already diagnosed to have HCC and visiting AKUH during 1999–2009 were identified using ICD code 1550. …

Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.

Prostate Specific Antigen As A Risk Factor For Skeletal Metastases In Black African Men With Prostate Cancer, Ayman Mahmood Qureshi

Master of Medicine in Imaging and Diagnostic Radiology

Background: Prostate cancer is one of the commonest cancers in men worldwide. Several recognised risk factors are associated with this disease, amongst them, race. Despite this, there is a paucity of data in the native African setting. The skeletal system is a common site of metastasis, its incidence increasing with increase in prostate specific antigen (PSA) levels. Bone scans are used to detect skeletal metastases. Its use in prostate cancer patients with abnormal but low PSA has been subject of debate. Objectives: To test the association of PSA levels with skeletal metastasis in men with histologically proven prostate cancer. Methodology: …

Cultural Diversity And Views On Alzheimer Disease In Older African Americans., Barry W. Rovner, Robin J. Casten, Lynn F. Harris

Department of Psychiatry and Human Behavior Faculty Papers

Cultural constructs prevalent in older African Americans may influence their risk perceptions and knowledge of Alzheimer disease (AD). To examine this issue, we administered 3 sociocultural scales, the AD Knowledge Scale, and a Risk Perception questionnaire to 271 older African Americans who were recruited from a large community senior center and local churches. Higher Present Time Orientation was significantly related to perceptions of having little control over risks to health (P=0.004), God's Will in determining AD (P=0.001), and lower AD knowledge (P

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Community Health Sciences

Background

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting.

Methods

We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

The Ccl5/Ccr5 Axis Promotes Metastasis In Basal Breast Cancer., Marco Velasco-Velázquez, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Recently, we have shown that the CCL5/CCR5 axis is active in patients affected by an aggressive basal subtype of breast cancer. Using preclinical models, we have demonstrated that CCR5 promotes breast cancer invasiveness and metastatic potential, while CCR5 inhibition abrogates them. Thus, CCR5 antagonists may constitute an alternative therapeutic approach for patients affected by metastatic basal breast cancer.

Anti-Helicobacter Pylori Activity And Inhibition Of Helicobacter Pylori-Induced Release Of Il-8 In Ags Cells By Plant Extracts, Javed Yakoob, Zaigham Abbas, Rustam Khan, Muhammad Waqas Usman, Saeed Hamid, Safia Awan, Kanza Shamim, Syed Faisal Zaidi, Toshiro Sugiyama, Wasim Jafri

Section of Gastroenterology

Plants used in popular diet were studied for anti-Helicobacter pylori activity and their effect on the expression of interleukin-8 (IL-8) from H. pylori infected gastric epithelial cells. Extracts were prepared of Allium sativum (A. sativum), Cuminum cyminum (C. cyminum),Piper nigrum (P. nigrum) and their mix in two different dilutions. AGS cell line and H. pyloristrains were used for co-culture experiments. Extracts bactericidal activity was determined by a viable colony count. ELISA (Enzyme linked immunosorbent assay) was used to determine IL-8 expression. DNA extracted from bacterial cells was used for polymerase chain reaction (PCR) …

Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught

Department of Biochemistry and Molecular Biology Faculty Papers

Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich …

Nutrition Intervention To Decrease Symptoms In Patients With Advanced Heart Failure, Terry A. Lennie, Debra K. Moser, Martha J. Biddle, Darlene Welsh, Geza G. Bruckner, D. Travis Thomas, Mary Kay Rayens, Alison L. Bailey

Nursing Faculty Publications

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, …

A Review Of G6pd Deficiency In Pakistani Perspective, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

The Perfect Fit

Colby Magazine

From the classrooms and laboratories of Mayflower Hill, they found their niche in science. Microbiologist Carrie Harwood ’73, transplant surgeon Patrick Wood ’75, and marine biologist Paul Wade ’80 have passion for their professions.

Nitric Oxide And Its Metabolites In The Critical Phase Of Illness: Rapid Biomarkers In The Making, Asad Mian, Mayank Aranke, Nathan S. Bryan

Department of Emergency Medicine

The potential of nitric oxide (NO) as a rapid assay biomarker, one that could provide a quantum leap in acute care, remains largely untapped. NO plays a crucial role as bronchodilator, vasodilator and inflammatory mediator. The main objective of this review is to demonstrate how NO is a molecule of heavy interest in various acute disease states along the emergency department and critical care spectrum: respiratory infections, central nervous system infections, asthma, acute kidney injury, sepsis, septic shock, and myocardial ischemia, to name just a few. We discuss how NO and its oxidative metabolites, nitrite and nitrate, are readily detectable …

Cell Death Pathways In Directly Irradiated Cells And Cells Exposed To Medium From Irradiated Cells, K.K. Jella, Amaya Garcia, Brendan Mcclean, Hugh Byrne, Fiona Lyng

Articles

Purpose: The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium. Materials and methods: Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy unit. For bystander experiments, the medium was harvested from donor HaCaT cells one hour after irradiation and transferred to recipient HaCaT cells. Clonogenic assay, apoptosis, necrosis, mitotic cell death, senescence and cell cycle analysis were measured in both directly irradiated cells and bystander cells Results: A reduction in cell survival was …

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Role Of Garlic Usage In Cardiovascular Disease Prevention: An Evidence-Based Approach, Waris Qidwai, Tabinda Ashfaq

Department of Family Medicine

Introduction:.Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. This study was done to find out the role of garlic usage in cardiovascular disease prevention.

Methodology : .Major databases including Google, PubMed,MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing …

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

Clinician-Performed Beside Ultrasound For The Diagnosis Of Traumatic Pneumothorax., Bon S. Ku, Jason M. Fields, Brendan Carr, Worth W Everett, Vincent H Gracias, Anthony J Dean

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Prior studies have reported conflicting results regarding the utility of ultrasound in the diagnosis of traumatic pneumothorax (PTX) because they have used sonologists with extensive experience. This study evaluates the characteristics of ultrasound for PTX for a large cohort of trauma and emergency physicians.

METHODS: This was a prospective, observational study on a convenience sample of patients presenting to a trauma center who had a thoracic ultrasound (TUS) evaluation for PTX performed after the Focused Assessment with Sonography for Trauma exam. Sonologists recorded their findings prior to any other diagnostic studies. The results of TUS were compared to one …

Assessment Of Early Tumor Response To Cytotoxic Chemotherapy With Dynamic Contrast-Enhanced Ultrasound In Human Breast Cancer Xenografts., Jian-Wei Wang, Wei Zheng, Ji-Bin Liu, Yao Chen, Long-Hui Cao, Rong-Zhen Luo, An-Hua Li, Jian-Hua Zhou

Department of Radiology Faculty Papers

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak …

Elevated Chemerin Levels In Pakistani Men: An Interrelation With Metabolic Syndrome Phenotypes, Syeda Sadia Fatima, Kiymet Bozaoglu, Rehana Rehman, Faiza Alam, Abdul Shakoor Memon

Department of Biological & Biomedical Sciences

Chemerin is a novel protein linked to adipocyte differentiation and the development of metabolic imbalances. We sought to examine the relationship of chemerin with metabolic syndrome disturbances including body fat percentage, serum lipid, glucose, insulin levels and body fat percentage in lean and obese volunteers. A cross-sectional study of 90 randomly selected healthy males from Pakistan were divided into three groups as per Body Mass Index (BMI) criteria for South Asian Population. Anthropometric measurements were taken for BMI, waist circumference, hip circumference and body fat percentage, while serum analyses were performed for fasting blood glucose, fasting insulin, fasting lipid profile …

Roles And Mechanism Of Mir-199a And Mir-125b In Tumor Angiogenesis., Jun He, Yi Jing, Wei Li, Xu Qian, Qing Xu, Feng-Shan Li, Ling-Zhi Liu, Bing-Hua Jiang, Yue Jiang

Computational Medicine Center Faculty Papers

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and …

Curatedovariandata: Clinically Annotated Data For The Ovarian Cancer Transcriptome, Benjamin Frederick Ganzfried, Markus Riester, Benjamin Haibe-Kains, Thomas Risch, Svitlana Tyekucheva, Ina Jazic, Xin Victoria Wang, Mahnaz Ahmadifar, Michael J. Birrer, Giovanni Parmigiani, Curtis Huttenhower, Levi Waldron

Publications and Research

This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software for reproducible preparation of similar databases. This resource provides uniformly prepared microarray data for 2970 patients from 23 studies with curated and documented clinical metadata. It allows users to efficiently identify studies and patient subgroups of interest for analysis and to perform meta-analysis immediately without the challenges posed by harmonizing heterogeneous microarray technologies, study designs, expression data processing methods and clinical data formats. We confirm that the recently proposed biomarker CXCL12 is associated with patient survival, independently of stage and optimal …

Data Mining The Functional Characterizations Of Proteins To Predict Their Cancer-Relatedness, Peter Revesz, Christopher Assi

School of Computing: Faculty Publications

This paper considers two types of protein data. First, data about protein function described in a number of ways, such as, GO terms and PFAM families. Second, data about whether individual proteins are experimentally associated with cancer by an anomalous elevation or lowering of their expressions within cancerous cells. We combine these two types of protein data and test whether the first type of data, that is, the functional descriptors, can predict the second type of data, that is, cancer-relatedness. By using data mining and machine learning, we derive a classifier algorithm that using only GO term and PFAM family …

A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

UNLABELLED: To enhance the research capabilities of investigators interested in Staphylococcus aureus, the Nebraska Center for Staphylococcal Research (CSR) has generated a sequence-defined transposon mutant library consisting of 1,952 strains, each containing a single mutation within a nonessential gene of the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300. To demonstrate the utility of this library for large-scale screening of phenotypic alterations, we spotted the library on indicator plates to assess hemolytic potential, protease production, pigmentation, and mannitol utilization. As expected, we identified many genes known to function in these processes, thus validating the utility of this approach. Importantly, we …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller

Dartmouth Scholarship

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Age-Related Accumulation Of T Cells With Markers Of Relatively Stronger Autoreactivity Leads To Functional Erosion Of T Cells., Zohreh Tatari-Calderone, Milica Stojakovic, Ramita Dewan, Gama L. Bouder, Dragana Jankovic, Stanislav Vukmanovic

Pediatrics Faculty Publications

Background

Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases.

Results

The phenotype of T cells …

Transient Receptor Potential (Trp) Channels And Cardiac Fibrosis, Zhichao Yue, Yanhui Zhang, Jia Xie, Jianmin Jiang, Lixia Yue

UCHC Articles - Research

Cardiac fibrosis is associated with most cardiac diseases. Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts. Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells. Myofibroblasts are hardly present in healthy normal heart tissue, but appear abundantly in diseased hearts. Cardiac fibroblasts are activated by a variety of pathological stimuli, such as myocardial injury, oxidative stress, mechanical stretch, and elevated autocrine-paracrine mediators, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. A number of signaling pathways and bioactive molecules are involved …