Digital Commons Network^™

Polymorphisms In Genes Of Tricarboxylic Acid Cycle Key Enzymes Are Associated With Early Recurrence Of Hepatocellular Carcinoma., Shaogui Wan, Yousheng Wu, Xingchun Zhou, Yibing Chen, Jiaze An, Xiaohe Yu, Huiqing Zhang, Hushan Yang, Jinliang Xing

Department of Medical Oncology Faculty Papers

Alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes have been indicated in several malignancies, including hepatocellular carcinoma (HCC). They play an important role in the progression of cancer. However, the impact of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes on the recurrence of HCC has not been investigated. In this study, we genotyped 17 SNPs in genes encoding TCA cycle key enzymes and analyzed their association with recurrence-free survival (RFS) in a cohort of 492 Chinese HCC patients by Cox proportional hazard model and survival tree analysis. We identified 7 SNPs in SDHC, …

Crosstalk Between Desmoglein 2 And Patched 1 Accelerates Chemical-Induced Skin Tumorigenesis., Donna M Brennan-Crispi, Claudia Hossain, Joya Sahu, Mary Brady, Natalia A Riobo, M G Mahoney

Department of Biochemistry and Molecular Biology Faculty Papers

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous …

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Urine Proteomics Identifies Preeclampsia Subphenotypes, Michelle R. Axe

Undergraduate Honors Thesis Projects

Preeclampsia is a perinatal complication of unknown etiology, resulting in 76,000 maternal deaths and 500,000 infant deaths annually₁. The Nationwide Children’s Center for Perinatal Research was the first cohort to propose that preeclampsia is rooted in protein misfolding. We aimed to characterize the misfolded protein components of maternal urine samples and to determine if distinct molecular profiles exist for clinical preeclampsia phenotypes. A total of 86 maternal urine samples from Yale-New Haven Hospital were analyzed for this study, from six clinical preeclampsia subphenotypes- pregnant control (n=10), idiopathic proteinuria (n=15), mild preeclampsia (n=14), superimposed preeclampsia (n=12), typical severe preeclampsia …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Polymeric Nanoparticle-Based Delivery Of Microrna-199a-3p Inhibits Proliferation And Growth Of Osteosarcoma Cells, Linlin Zhang, Arun K. Iyer, Xiaoqian Yang, Eisuke Kobayashi, Yuqi Guo, Henry Mankin, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain …

The Effects Of Nutrition And Physical Activity Education On Knowledge And Glycemic Control Among Persons With Type 2 Diabetes, Alexandra Harris

Evidence-Based Practice Project Reports

Diabetes affects millions of people worldwide. Approximately 29.1 million people or 9.3% of the United States population has diabetes (Centers for Disease Control (CDC), 2014). Diabetes was the seventh leading cause of death in the United States in 2010 and is projected by the World Health Organization (WHO) to be the seventh leading cause of death globally by 2030. The purpose of this evidence-based project was to provide nutrition and physical activity education in an effort to improve diabetes knowledge and glycemic control among persons with type 2 diabetes. Hemoglobin A1c levels and Diabetes Knowledge Test scores were compared from …

Successful Isolation Of Viable Adipose-Derived Stem Cells From Human Adipose Tissue Subject To Long-Term Cryopreservation: Positive Implications For Adult Stem Cell-Based Therapeutics In Patients Of Advanced Age., Sean Devitt, Md, Cynthia M Carter, Raia Dierov, Scott Weiss, Robert P Gersch, Ivona Percec

Jefferson Hospital Staff Papers and Presentations

We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved2 years, irrespective of patient age. However, this difference did not persist with continued growth and …

Targeted Single Molecule Sequencing Methodology For Ovarian Hyperstimulation Syndrome., Funda Orkunoglu-Suer, Arthur F. Harralson, David Frankfurter, Paul Gindoff, Travis J. O'Brien

Genomics and Precision Medicine Faculty Publications

BACKGROUND: One of the most significant issues surrounding next generation sequencing is the cost and the difficulty assembling short read lengths. Targeted capture enrichment of longer fragments using single molecule sequencing (SMS) is expected to improve both sequence assembly and base-call accuracy but, at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. We developed a targeted single molecule sequencing (T-SMS) panel for genes implicated in ovarian response to controlled ovarian hyperstimulation (COH) for infertility.

RESULTS: Target enrichment was carried out using droplet-base multiplex polymerase chain reaction (PCR) technology (RainDance®) …

Com Outlook Spring 2015, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Exploring Racial Disparity In St. Louis City Fetal-Infant Death, Hadi Danawi, Marie Peoples

Walden Faculty and Staff Publications

The perinatal periods of risk (PPOR) methodology was used to analyze resident fetal and infant deaths in St. Louis City, Missouri, for the years 1999 - 2008. The PPOR approach is mapped into four periods: Maternal Health/Prematurity (MHP), Maternal Care (MC), Newborn Care (NC), and Infant Health (IF). Both Blacks and Whites experienced excess fetal-infant death within the MHP periods. Recognizing specific periods of increased risk provides key information to transform data into action. Findings allow childbirth educators, community members, and policy-makers to further explore barriers limiting maternal care.

The Therapeutic Role Of Turmeric In Treatment And Prevention Of Alzheimer’S Disease, Rylan M. Mcquade

Selected Honors Theses

As a devastating neurological condition that expends millions of lives each year, Alzheimer’s disease (AD) is a subject of intense investigation.¹ Although AD has been known for over a century, the precise mechanisms that underlie AD pathogenesis and development are still poorly understood. The Alzheimer phenotype is typified by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), causing researchers to notice several key enzymes implicated in this process.¹ Most notable are β and γ secretases (which drive Aβ plaque production) and phospholipase

A₂ (which stimulates major cascade activation through the specific cleavage of fatty acyl esters). …

Ubiquitous L1 Mosaicism In Hippocampal Neurons., Kyle R. Upton, Daniel J. Gerhardt, J. Samuel Jesuadian, Sandra R. Richardson, Francisco J. Sánchez-Luque, Gabriela O. Bodea, Adam D. Ewing, Carmen Salvador-Palomeque, Marjo S. Van Der Knaap, Paul M. Brennan, Adeline Vanderver, Geoffrey J. Faulkner

Neurology Faculty Publications

Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source of genotypic variation among neurons. As a neurogenic niche, the hippocampus supports pronounced L1 activity. However, the basal parameters and biological impact of L1-driven mosaicism remain unclear. Here, we performed single-cell retrotransposon capture sequencing (RC-seq) on individual human hippocampal neurons and glia, as well as cortical neurons. An estimated 13.7 somatic L1 insertions occurred per hippocampal neuron and carried the sequence hallmarks of target-primed reverse transcription. Notably, hippocampal neuron L1 insertions were specifically enriched in transcribed neuronal stem cell enhancers and hippocampus genes, increasing their probability of functional relevance. In …

The Role Of Ultrasound In The Lebanese Outreach Setting, Reem Abu-Rustum, Fouad M. Ziade, Hadi Danawi

Walden Faculty and Staff Publications

A cross-sectional study was carried out on 669 patients to assess the role of introducing ultrasound into obstetrical outreach in Lebanon. Data were collected, and descriptive statistics were performed. Sonographic findings were compared using Chi-square tests between underserved Lebanese and Syrian refugee mothers. Ultrasound plays a significant role in properly dating pregnancies in addition to identifying at-risk fetuses and detecting placental abnormalities. Medical providers need to make sonographic evaluation in the Lebanese outreach obstetrical setting more available and more systematic in order to secure a safe outcome for underserved Lebanese and Syrian refugee mothers and offspring.

Physical Actvity In Pregnant Rat Dams Reduces Mammary Tumor Formation In Offspring, Leon Clah

Open Access Theses

Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer death among women. Lifestyle factors such as physical activity and diet play a role in attenuating the incidence of breast cancer. Current research is beginning to show that exercise during pregnancy can convey long term health benefits to offspring. In light of these studies, the goal of this project was to determine if maternal physical activity during pregnancy could lead to reduced mammary tumor development in female offspring. Towards this goal, female Sprague Dawley rats were divided into two groups, sedentary and exercise, with the exercise …

Image Enhancement Of Cancerous Tissue In Mammography Images, Richard Thomas Richardson

CCAC Theses and Dissertations

This research presents a framework for enhancing and analyzing time-sequenced mammographic images for detection of cancerous tissue, specifically designed to assist radiologists and physicians with the detection of breast cancer. By using computer aided diagnosis (CAD) systems as a tool to help in the detection of breast cancer in computed tomography (CT) mammography images, previous CT mammography images will enhance the interpretation of the next series of images. The first stage of this dissertation applies image subtraction to images from the same patient over time. Image types are defined as temporal subtraction, dual-energy subtraction, and Digital Database for Screening Mammography …

Oncolog, Volume 60, Number 04, April 2015, Jill Delsigne, Joe Munch, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Multidisciplinary Globe-Sparing Treatment for Lacrimal Gland Carcinoma Preserves Vision and Minimizes Morbidity: Until recently, the treatment of lacrimal gland carcinoma almost always required removal of the eye. But for some patients with these tumors, globe-sparing surgery followed by radiation therapy can preserve vision and decrease ocular morbidity and facial disfigurement.
• Novel Trial Design Streamlines Development of Breast Cancer Therapies: Developing a cancer-fighting drug can take around a billion dollars and a dozen or more years. Even then, fail in clinical trials. To identify effective cancer therapies more quickly and efficiently, researchers have tuned to an innovative clinical model in which …

Transient Cardiovascular Hemodynamics In A Patient-Specific Arterial System, Jr Rodward Hewlin

Dissertations

The ultimate goal of the present study is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present study a full cardiovascular experimental phantom and digital phantom (CFD model) was fabricated to study: (1) the effects of local hemodynamics on global hemodynamics, (2) the effects of transition from bed-rest to upright position, and (3) transport of dye (drug delivery) in the arterial system. Computational three dimensional (3-D) models (designs A, B, and C) …

Eradication Of Advanced Pelvic Hydatid Bone Disease After Limb Salvage Surgery - 5-Year Follow-Up: A Case Report, Muhammad Shahid Khan, Pervaiz Hashmi, Dawar Khan

Department of Surgery Docs

Abstract

INTRODUCTION:

Echinococcosis is produced by the larval stage of Echinococcus granulosus; it is a parasitic disease which is seen rarely in humans and has adverse outcomes. We report a case of advanced pelvic hydatid bone disease with successful limb salvage surgery. Our patient had a 5-year follow-up without recurrence which is a rarity as per the literature. Early diagnosis and prompt medical therapy are necessary for effective management whereas delayed diagnosis is always fraught with the risk of recurrence and sepsis.

CASE PRESENTATION:

In 2009, a 30-year-old woman, native of Karachi (Sindhi ethnicity), presented at our clinic with history …

Does The Addition Of Dexamethasone To Local Anesthetic Used For Peripheral Nerve Block Prolong Analgesia In The Surgical Patient?, Janice M. Oliveira

Nurse Anesthesia MSNA Student Capstones

Pain after orthopedic surgery can be intense. Many anesthesia providers and orthopedic surgeons support the use of peripheral nerve blockade to assist in decreasing the amount of pain a patient may experience post operatively. Select medication adjuncts are being added to peripheral nerve blocks to prolong analgesia. The research presented here focuses on the addition of dexamethasone to peripheral nerve blocks to prolong analgesia. Dexamethasone is a synthetic glucocorticoid that acts as an anti-inflammatory. It has been shown to inhibit the release of inflammatory mediators such as, interleukins and cytokines, facilitating the release of anti-inflammatory mediators, decreasing postoperative pain. Recent …

Mindfulness: Being Present In The Moment, Stephanie Ann Stathas, Christine Frazer

Walden Faculty and Staff Publications

This article serves to enlighten childbirth educators’ knowledge about mindfulness and the mother-baby benefits associated with incorporating mindfulness- based interventions into practice. Jon Kabat-Zinn, who developed the Mindfulness Based Stress Reduction program, brought the concept of mindfulness into the world of healthcare and mainstream society. Mindfulness is the practice of bringing awareness to the here and now using a variety of methods. Nancy Bardacke has taken the practice of mindfulness further and developed a program for expecting mothers, known as Mindfulness Based Childbirth and Parenting. This program has been shown to reduce stress responses that may be harmful to a …

Prevalence Of Rheumatoid Arthritis In Low-And Middle-Income Countries: A Systematic Review And Analysis, Igor Rudan, Simrita Sidhu, Angeliki Papana, Shi–Jiao Meng, Yu Xin-Wei, Wei Wang, Ruth M. Campbell–Page, Alessandro Rhyll Demaio, Harish Nair, Devi Sridhar, Evropi Theodoratou, Ben Dowman, Davies Adeloye, Azeem Majeed, Josip Car, Harry Campbell, Wei Wang, Kit Yee Chan

Research outputs 2014 to 2021

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that affects the small joints of the body. It is one of the leading causes of chronic morbidity in high–income countries, but little is known about the burden of this disease in low– and middle–income countries (LMIC).

Methods: The aim of this study was to estimate the prevalence of RA in six of the World Health Organization's (WHO) regions that harbour LMIC by identifying all relevant studies in those regions. To accomplish this aim various bibliographic databases were searched: PubMed, EMBASE, Global Health, LILACS and the Chinese databases CNKI and WanFang. Studies …

Quality Of Life Among Women With Symptoms Of Gynecological Morbidities: Results Of A Cross‐Sectional Study In Karachi, Pakistan, Neelofar Sami, Tazeen Saeed Ali, Muhammad Osama

Community Health Sciences

AIMS:

A population-based cross-sectional study design was used to study the effects of symptoms of various gynecological morbidities (GM) on health-related quality of life (HRQoL) of women, residents of squatter settlements of Karachi, Pakistan.

MATERIAL AND METHODS:

This cross-sectional study was conducted in squatter settlements of Karachi from September 2012 to August 2013, with 1002 married, non-pregnant women. After obtaining written informed consent from every participant, a structured questionnaire was used to collect information about symptoms of GM and their effect on four domains of HRQoL (physical, social, functional and financial domains).

RESULTS:

Of 1002 women who participated in the …

Short-Wavelength Enrichment Of Polychromatic Light Enhances Human Melatonin Suppression Potency., George Brainard, John P. Hanifin, Benjamin Warfield, Marielle K. Stone, Mary E. James, Melissa Ayers, Alan Kubey, Brenda Byrne, Mark Rollag

Department of Neurology Faculty Papers

The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short-wavelength visible light in the blue-appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short-wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy …

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

Complementary And Alternative Medicine In Cancer Prevention And Therapy., Peng Cao, Senthamil R Selvan, Esra Küpeli Akkol, Ning Wang, Hongjun Yang, Xiaolan Cheng

Department of Medical Oncology Faculty Papers

No abstract provided.

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis, Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

The Cognitive Effects Of Chronic Malnutrition And Environment On Working Memory And Executive Function In Children, Kristiana E. Morgan

Independent Study Project (ISP) Collection

Chronic malnutrition, or stunting, occurs frequently in many developing countries such as Uganda. Stunting hinders physical growth and has been associated with delayed cognitive development, especially in young children. This study examined the effect of stunted growth on the function of cognitive processes involving the working memory and executive functions using neuropsychological assessments. Additionally, this study compared cognitive performances among rural and urban populations to analyze the environmental background differences which may affect cognition.

Population samples of fifteen five year old children classified as rural adequately nourished, rural stunted and urban adequately nourished were examined. Tests for working memory and …

The Effect Of Exercise Training On Skeletal Muscle Gdnf Content And Neuromuscular Physiology In A Mouse Model Of Amyotrophic Lateral Sclerosis., Nicole Carpp

Honors Theses

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by the loss of motor neurons, leading to paralysis and death. Glial cell line-derived neurotrophic factor (GDNF) promotes neuron health and function and has been proposed as a therapeutic treatment for ALS. GDNF protein expression in skeletal muscle is regulated by physical activity. The aim of this study was to determine if low intensity exercise would increase GDNF expression in skeletal muscle and slow degeneration of motor neurons in a mouse model of ALS. Following the first sign of disease onset, transgenic ALS mice were randomly assigned to one of three …