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Improving Aav Transduction Efficiency In Retinal Bipolar Cells For Optogenetic Vision Restoration, Shengjie Cui Jan 2018

Improving Aav Transduction Efficiency In Retinal Bipolar Cells For Optogenetic Vision Restoration, Shengjie Cui

Wayne State University Dissertations

Recombinant adeno-associated virus (AAV) vectors are the most promising vehicles for therapeutic gene delivery to the retina. We are developing AAV-mediated expression of optogenetic tools in surviving inner retinal neurons as a potential strategy to restoring vision after the death of photoreceptor cells in retinal degeneration. Targeting optogeneitc tools, such as channelrhodopsin-2 (ChR2), to retinal bipolar cells (RBCs) is particularly attractive. In particular, our lab has recently developed an optimized mGluR6 promoter-based virus vector that can mainly target ChR2 to rod bipolar cells. However, AAV-mediated transduction efficiency in RBCs is relatively low. The transduction efficiency could be affected by a …


Inflammation In The Pathogenesis Of Diabetic Retinopathy, Haoshen Shi Jan 2018

Inflammation In The Pathogenesis Of Diabetic Retinopathy, Haoshen Shi

Wayne State University Dissertations

The general purpose of these studies is to investigate inflammation in diabetic retinopathy in an effort to identify key intervention points to develop as treatments. Firstly, we showed that the neuropeptide VIP displayed protective immunoregulatory effects on retinal endothelial cells cultured under high glucose conditions. This effect was carried out, in part through the VPAC2 receptor.

Next, we studied the β-adrenergic receptor agonist, Compound 49b, and its effect on the pro-resolving RvD1 pathway. Compound 49b was previously shown to suppress both inflammatory and apoptotic responses in DR. We demonstrated that Compound 49b rescued the high glucose-induced decrese in RvD1 and …


Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects At Risk For Type 1 Diabetes, Robert Z. Harms, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Victoria B. Smith, Lynette M. Smith, Peter Gottlieb, Nora Sarvetnick Jan 2018

Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects At Risk For Type 1 Diabetes, Robert Z. Harms, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Victoria B. Smith, Lynette M. Smith, Peter Gottlieb, Nora Sarvetnick

Journal Articles: Surgery

We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted …


Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh Jan 2018

Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh

Journal Articles: Eppley Institute

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small …


Met Receptor Inhibitor Su11274 Localizes In The Endoplasmic Reticulum, Edwin J. Wiest, Heather Jensen Smith, Michael A. Hollingsworth Jan 2018

Met Receptor Inhibitor Su11274 Localizes In The Endoplasmic Reticulum, Edwin J. Wiest, Heather Jensen Smith, Michael A. Hollingsworth

Journal Articles: Eppley Institute

We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum.


Mir-133a Mimic Alleviates T1dm-Induced Systolic Dysfunction In Akita: An Mri-Based Study, Shyam S. Nandi, Hamid R. Shahshahan, Quanliang Shang, Shelby Kutty, Michael D. Boska, Paras K. Mishra Jan 2018

Mir-133a Mimic Alleviates T1dm-Induced Systolic Dysfunction In Akita: An Mri-Based Study, Shyam S. Nandi, Hamid R. Shahshahan, Quanliang Shang, Shelby Kutty, Michael D. Boska, Paras K. Mishra

Journal Articles: Pediatrics

Diabetic cardiomyopathy is a leading cause of heart failure. Developing a novel therapeutic strategy for diabetic cardiomyopathy and characterizing animal models used for diabetes mellitus (DM) are important. Insulin 2 mutant (Ins2+/-) Akita is a spontaneous, genetic, mouse model for T1DM, which is relevant to humans. There are contrasting reports on systolic dysfunction and pathological remodeling (hypertrophy and fibrosis) in Akita heart. Here, we used magnetic resonance imaging (MRI) approach, a gold standard reference for evaluating cardiac function, to measure ejection fraction (indicator of systolic dysfunction) in Akita. Moreover, we performed Wheat Germ Agglutinin (WGA) and hematoxylin and …


Selective Infarct Zone Imaging With Intravenous Acoustically Activated Droplets, Songita A. Choudhury, Feng Xie, Shelby Kutty, John Lof, Elizabeth Stolze, Thomas R. Porter Jan 2018

Selective Infarct Zone Imaging With Intravenous Acoustically Activated Droplets, Songita A. Choudhury, Feng Xie, Shelby Kutty, John Lof, Elizabeth Stolze, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Microbubbles (MB) can be compressed to nanometer-sized droplets and reactivated with diagnostic ultrasound; these reactivated MB possess unique imaging characteristics.

OBJECTIVE: We hypothesized that droplets formed from compressing Definity MB may be used for infarct-enhancement imaging.

METHODS: Fourteen rats underwent ligation of their left anterior descending (LAD) artery, and five pigs underwent 90 minute balloon occlusions of their mid LAD. At 48 hours in rats, transthoracic ultrasound was performed at two and four minutes following 200 μL intravenous injections (IVI) of Definity droplets (DD), at which point the MI was increased from 0.5 to 1.5 to assess for a …


Testosterone And The Adult Male, Alex Straftis Jan 2018

Testosterone And The Adult Male, Alex Straftis

Calvert Undergraduate Research Awards

Abstract

In the last 15 years, prescription testosterone sales have increased almost threefold. Testosterone is a powerful hormone, which has both physiological and behavioral effects on the adult male. These effects vary over a man’s life course and social ecology. In a natural setting, testosterone reaches a peak during early adulthood, declines gradually over midlife, and has exponential drops after the age of 70. Increasing testosterone, through testosterone replacement therapy (TRT), past early adulthood, is an evolutionary novel circumstance for an adult male. To gauge these effects, and the motivations that initiated them, this study conducted a preliminary text analysis …


Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy, Justin M. Canada Jan 2018

Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy, Justin M. Canada

Theses and Dissertations

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and …


Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara Jan 2018

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2; every …


Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo Jan 2018

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …


Development Of Novel Models To Study Deep Brain Effects Of Cortical Transcranial Magnetic Stimulation, Farheen Syeda Jan 2018

Development Of Novel Models To Study Deep Brain Effects Of Cortical Transcranial Magnetic Stimulation, Farheen Syeda

Theses and Dissertations

Neurological disorders require varying types and degrees of treatments depending on the symptoms and underlying causes of the disease. Patients suffering from medication-refractory symptoms often undergo further treatment in the form of brain stimulation, e.g. electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or transcranial magnetic stimulation (TMS). These treatments are popular and have been shown to relieve various symptoms for patients with neurological conditions. However, the underlying effects of the stimulation, and subsequently the causes of symptom-relief, are not very well understood. In particular, TMS is a non-invasive brain stimulation therapy which uses time-varying magnetic …


Global Mapping Of Transcription Factor Motifs In Human Aging., David Alfego, Ulrich Rodeck, Andres Kriete Jan 2018

Global Mapping Of Transcription Factor Motifs In Human Aging., David Alfego, Ulrich Rodeck, Andres Kriete

Department of Dermatology and Cutaneous Biology Faculty Papers

Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established …


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Eun Hee Kwon, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood Jan 2018

Brain Is A Potential Sanctuary For Subtype C Hiv-1 Irrespective Of Art Treatment Outcome, For Yue Tso, Guobin Kang, Peter Julius, Qingsheng Li, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Subtype C HIV-1 is responsible for the largest proportion of people living with HIV-1 infection. However, there is limited information about the roles of the brain and its cell types as a potential sanctuary for this subtype and how the sanctuary may be affected by the administration of anti-retroviral therapy (ART). To address this issue, we collected postmortem brain tissues from ART treated HIV-1 infected Zambian individuals who experienced complete viral suppression and those who did not. Tissues from various brain compartments were collected from each individual as frozen and formalin-fixed paraffin embedded brain specimens, for detection and quantification of …


Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang Jan 2018

Contribution Of The Gp120 V3 Loop To Envelope Glycoprotein Trimer Stability In Primate Immunodeficiency Viruses, Dane Bowder, Haley Hollingsead, Kate Durst, Duoyi Hu, Wenzhong Wei, Joshua Wiggins, Halima Medjahed, Andrés Finzi, Joseph Sodroski, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and …


Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard Jan 2018

Ultrastructure Of Meelsvirus: A Nuclear Virus Of Arrow Worms (Phylum Chaetognatha) Producing Giant "Tailed" Virions, George L. Shinn, Brianna L. Bullard

Nebraska Center for Virology: Faculty Publications

Most known giant viruses, i.e., viruses producing giant virions, parasitize amoebae and other unicellular eukaryotes. Although they vary in the level of dependence on host nuclear functions, their virions self-assemble in the host cell's cytoplasm. Here we report the discovery of a new prototype of giant virus infecting epidermal cells of the marine arrow worm Adhesisagitta hispida. Its 1.25 μm-long virions self-assemble and accumulate in the host cell's nucleus. Conventional transmission electron microscopy reveals that the virions have a unique bipartite structure. An ovoid nucleocapsid, situated in a broad "head" end of the virion is surrounded by a thin …


In Vitro Digestion And Characterization Of 2s Albumin And Digestion-Resistant Peptides In Pecan, Jelena Spiric, Stef J. Koppelman, Andre Knulst, Julie A. Nordlee, Steve L. Taylor, Joseph L. Baumert Jan 2018

In Vitro Digestion And Characterization Of 2s Albumin And Digestion-Resistant Peptides In Pecan, Jelena Spiric, Stef J. Koppelman, Andre Knulst, Julie A. Nordlee, Steve L. Taylor, Joseph L. Baumert

Department of Food Science and Technology: Faculty Publications

The 2S albumins are one of the major protein families involved in severe food allergic reactions to nuts, seeds, and legumes, thus potentially making these proteins clinically relevant for allergic sensitization and potential diagnostic markers. In this study, we sought to purify native 2S albumin protein from pecan to further characterize this putative allergen. The purified 2S albumin, Car i 1, from pecan was found to be resistant to digestion by pepsin in simulated gastric fluid (SGF) and comparatively stable to proteolysis by trypsin and pancreatin in simulated intestinal fluid (SIF). Digestion of purified Car i 1 in SGF and …


Role Of Microbes In The Development Of Alzheimer's Disease: State Of The Art - An International Symposium Presented At The 2017 Iagg Congress In San Francisco., Tamàs Fülöp, Ruth F Itzhaki, Brian J. Balin Phd, Judith Miklossy, Annelise E Barron Jan 2018

Role Of Microbes In The Development Of Alzheimer's Disease: State Of The Art - An International Symposium Presented At The 2017 Iagg Congress In San Francisco., Tamàs Fülöp, Ruth F Itzhaki, Brian J. Balin Phd, Judith Miklossy, Annelise E Barron

PCOM Scholarly Works

This article reviews research results and ideas presented at a special symposium at the International Association of Gerontology and Geriatrics (IAGG) Congress held in July 2017 in San Francisco. Five researchers presented their results related to infection and Alzheimer's disease (AD). Prof. Itzhaki presented her work on the role of viruses, specifically HSV-1, in the pathogenesis of AD. She maintains that although it is true that most people harbor HSV-1 infection, either latent or active, nonetheless aspects of herpes infection can play a role in the pathogenesis of AD, based on extensive experimental evidence from AD brains and infected cell …


Advanced Cancer Patients' Medical Decision-Making While Experiencing Financial Toxicity, Heather L. Morel Jan 2018

Advanced Cancer Patients' Medical Decision-Making While Experiencing Financial Toxicity, Heather L. Morel

Walden Dissertations and Doctoral Studies

Financial toxicity (FT) is the impact that out of pocket (OOP) costs of cancer care have on patients' well-being, leading to lower quality of life, less compliance with prescribed therapy, and poorer outcomes, including increased mortality. The purpose of this study was to understand the impact of FT on advanced cancer patients' lives and their health care decision-making. Fuzzy trace theory provided the framework for examining how patients use gist and verbatim when making health care decisions while experiencing FT. Gist refers to main ideas that are often infused with emotional overlays that people use to make risky decisions, while …


Child Sexual Abuse And Prenatal Care: Understanding Screening, Modifications, And Proper Care, Wendy Abbott-Egnor Jan 2018

Child Sexual Abuse And Prenatal Care: Understanding Screening, Modifications, And Proper Care, Wendy Abbott-Egnor

Walden Dissertations and Doctoral Studies

Research has shown that 1 in 9 women in prenatal care have a history of childhood sexual abuse. Pregnant women with a history of childhood sexual abuse are at increased risk of depression, somatization, preterm contractions, posttraumatic stress symptomology, and re-traumatization. The purpose of this study was to bridge the gap in literature between research and practice. Data was collected from practitioners regarding the care and treatment of pregnant women with a childhood sexual abuse history. It was hypothesized that screening practices and modification to care and treatment based on practitioner knowledge of prior sex abuse history will vary by …


Oral Glucose Insulin Secretion Test For Identifying Patients With Insulin Resistance, David Kershner Jan 2018

Oral Glucose Insulin Secretion Test For Identifying Patients With Insulin Resistance, David Kershner

Walden Dissertations and Doctoral Studies

Insulin resistance is an increasing public health issue with the current literature, suggesting reduced sensitivity of insulin leads to adult onset diabetes and associated downstream pathologies that reduce life expectancy. The main objectives of this study were to evaluate the ability of the Oral Glucose Insulin Secretion Test (OGIST) to identify insulin resistance and examine differences in the insulin sensitivity based on gender, age, and ethnicity. This study was supported by the insulin resistance theory which focuses on the reduced ability of insulin to bind to the cellular insulin receptor, reducing the sensitivity of insulin. The OGIST lab results of …


Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack Jan 2018

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …


Sedentary Time And The Cumulative Risk Of Preserved And Reduced Ejection Fraction Heart Failure: From The Multi-Ethnic Study Of Atherosclerosis, Brandi Scot Rariden Jan 2018

Sedentary Time And The Cumulative Risk Of Preserved And Reduced Ejection Fraction Heart Failure: From The Multi-Ethnic Study Of Atherosclerosis, Brandi Scot Rariden

UNF Graduate Theses and Dissertations

ABSTRACT

Purpose: The purpose of this study was to examine the relationship between self-reported sedentary time (ST) and the cumulative risk of preserved ejection fraction heart failure (HFpEF) and reduced ejection fraction heart failure (HFrEF) using a diverse cohort of U.S. adults 45-84 years of age.

Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects (52.9% female). All were free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with baseline ST and risk of overall heart failure (HF), HFpEF, and HFrEF. Weekly self-reported ST was dichotomized …


Prevalence Of Hla-B*5701 In A Kenyan Population With Hiv Infection, Reena Shah, H. Nabiswa, Nancy Okinda, Gunturu Revathi, Mark Hawken, Nelson M. Jan 2018

Prevalence Of Hla-B*5701 In A Kenyan Population With Hiv Infection, Reena Shah, H. Nabiswa, Nancy Okinda, Gunturu Revathi, Mark Hawken, Nelson M.

Internal Medicine, East Africa

We read with interest the article published in your Journal entitled “Real-world persistence with antiretroviral therapy for HIV in the United Kingdom: a multicentre retrospective cohort study”1 which concluded that treatment discontinuation attributable to toxicity profile is not an uncommon event. They also acknowledged lack of data collection on HLA-B*5701 status, which would heavily influence initial ART regimen and the choice to discontinue medication. Of the 25.6 million living with Human Immunodeficiency Virus (HIV) in Africa, an estimated 1.6 million people live in Kenya.2 With an HIV prevalence of 5.6%, Kenya has upscaled HIV treatment and care in the past …


Women And The Experience Of Pain And Opioid Use Disorder: A Literature-Based Commentary, Andrew L. Koons, Marna R. Greenberg Do, Mph, Facep, Robert D. Cannon Do, Gillian A. Beauchamp Md Jan 2018

Women And The Experience Of Pain And Opioid Use Disorder: A Literature-Based Commentary, Andrew L. Koons, Marna R. Greenberg Do, Mph, Facep, Robert D. Cannon Do, Gillian A. Beauchamp Md

Department of Emergency Medicine

It is generally understood that pain experience and opioid abuse have relied on male-dominated models. However, sex and gender play a role in both pain experience and opioid use disorder.

Using the previously validated Texas Tech University Health Sciences Center Sex and Gender Specific Health PubMed Advanced Search Tool, the authors used pertinent literature to develop this literature-based commentary on sex and gender differences in pain experience and opioid use disorder. Women report their experience of pain more frequently, have increased rates of diagnoses related to pain, have increased pain sensitivity, and have a variable response to pain and analgesia. …


Determination Of An Optimal Response Cut-Off Able To Predict Progression-Free Survival In Patients With Well-Differentiated Advanced Pancreatic Neuroendocrine Tumours Treated With Sunitinib: An Alternative To The Current Recist-Defined Response., Angela Lamarca, Jorge Barriuso, Matthew Kulke, Ivan Borbath, Heinz-Josef Lenz, Jean Luc Raoul, Neal J. Meropol, Catherine Lombard-Bohas, James Posey, Sandrine Faivre, Eric Raymond, Juan W. Valle Jan 2018

Determination Of An Optimal Response Cut-Off Able To Predict Progression-Free Survival In Patients With Well-Differentiated Advanced Pancreatic Neuroendocrine Tumours Treated With Sunitinib: An Alternative To The Current Recist-Defined Response., Angela Lamarca, Jorge Barriuso, Matthew Kulke, Ivan Borbath, Heinz-Josef Lenz, Jean Luc Raoul, Neal J. Meropol, Catherine Lombard-Bohas, James Posey, Sandrine Faivre, Eric Raymond, Juan W. Valle

Department of Medical Oncology Faculty Papers

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.

METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) …


The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey Jan 2018

The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey

UROP Posters

The aim of this study is to observe cell proliferation, cell viability, apoptosis, and autophagy on acute myeloid leukemia (AML) cell lines, NB4 and U937, with the drug repurposing of mefloquine (MQ). Methods such as the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and trypan blue staining have shown a decrease in live cells with high concentrations of mefloquine. Using their average perspective IC50 values of MQ concentration, Western blotting was applied by means of apoptosis and autophagy markers to determine if the induction of apoptosis and inhibition of autophagy was present in MQ-treated AML cells. The experiment will be continued with more …


The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, Nujuma A. Moussa Jan 2018

The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, Nujuma A. Moussa

UROP Posters

Abstract: The Effect of DNA Methylation on TP73 Expression in Tumorgenesis

Nujuma Moussa, Zhixing Yao, Zaki A. Sherif

Department of Biochemistry & Molecular Biology, Howard University College of Medicine

TP73 is a member of the TP53 family of proteins that acts as a transcription factor to help regulate cellular distress. This tumor protein may play a dual role as a tumor suppressor and tumor promoter. The TP73 gene is mapped to chromosome 1p36, a frequently deleted region in neuroblastoma and other types of tumors. While mutations in the TP53 gene are commonly known to cause noxious cancers, 30% of cancers …


Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth Jan 2018

Cone Phosphodiesterase-6Γ’ Subunit Augments Cone Pde6 Holoenzyme Assembly And Stability In A Mouse Model Lacking Both Rod And Cone Pde6 Catalytic Subunits, Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth

Faculty & Staff Scholarship

Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α’ catalytic subunits and two identical cone-specific PDE6γ’ inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α’ subunits. Both rod and …