Medicine and Health Sciences Commons^™

Comparison Of Bacterial Culture With Biofire® Filmarray® Multiplex Pcr Screening Of Archived Cerebrospinal Fluid Specimens From Children With Suspected Bacterial Meningitis In Nigeria, S Obaro, F Hassan-Hanga, N Medugu, Rasaq Olaosebikan, G Olanipekun, B Jibir, S Gambo, Theresa Ajose, Carissa Duru, B Ebruke, H D Davies

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.

METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting …

Guanylyl Cyclase C As A Diagnostic And Therapeutic Target In Colorectal Cancer, Adi Caspi, Ariana A. Entezari, Madison Crutcher, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancer remains a major cause of mortality in the USA, despite advances in prevention and screening. Existing therapies focus primarily on generic treatment such as surgical intervention and chemotherapy, depending on disease severity. As personalized medicine and targeted molecular oncology continue to develop as promising treatment avenues, there has emerged a need for effective targets and biomarkers of colorectal cancer. The transmembrane receptor guanylyl cyclase C (GUCY2C) regulates intestinal homeostasis and has emerged as a tumor suppressor. Further, it is universally expressed in advanced metastatic colorectal tumors, as well as other cancer types that arise through intestinal metaplasia. In …

Functional Assessment Of Missense Variants In The Abcc6 Gene Implicated In Pseudoxanthoma Elasticum, A Heritable Ectopic Mineralization Disorder., Luke Kowal, Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E Snook, Jouni Uitto, Qiaoli Li

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6

Ondansetron To Reduce Neonatal Opioid Withdrawal Severity: A Randomized Clinical Trial, Gary Peltz, Lauren M. Jansson, Susan Adeniyi-Jones, Carol Cohane, David Drover, Steven Shafer, Meiyue Wang, Manhong Wu, Balaji Govindaswami, Priya Jegatheesan, Cynthia Argani, Salwa Kahn, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Objective
To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS).

Study Design
A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days.

Results
Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p>0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p=0.02). A non-significant trend was noted for the duration of …

Hoxa9 Overexpression Contributes To Stem Cell Overpopulation That Drives Development And Growth Of Colorectal Cancer, Brian Osmond, Caroline O.B. Facey, Chi Zhang, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

HOX proteins are transcription factors that regulate stem cell (SC) function, but their role in the SC origin of cancer is under-studied. Aberrant expression of HOX genes occurs in many cancer types. Our goal is to ascertain how retinoic acid (RA) signaling and the regulation of HOXA9 expression might play a role in the SC origin of human colorectal cancer (CRC). Previously, we reported that aldehyde dehydrogenase (ALDH) and other RA pathway components are co-expressed in colonic cancer SCs (CSCs) and that overpopulation of ALDH-positive CSCs occurs during colon tumorigenesis. Our hypothesis is RA signaling regulates HOXA9 expression, and dysregulated …

Age Moderates The Effect Of Injury Severity On Functional Trajectories In Traumatic Brain Injury: A Study Using The Nidilrr Traumatic Brain Injury Model Systems National Dataset., Laraine Winter, Janell L Mensinger, Helene J Moriarty, Keith M Robinson, Michelle Mckay, Benjamin E Leiby

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Age is a risk factor for a host of poor outcomes following traumatic brain injury (TBI), with some evidence suggesting that age is also a source of excess disability. We tested the extent to which age moderates the effect of injury severity on functional trajectories over 15 years post injury. Data from 11,442 participants from the 2020 National Institute of Disability and Independent Living Rehabiitation Research (NIDILRR) Traumatic Brain Injury Model Systems (TBIMS) National Dataset were analyzed using linear mixed effects models. Injury severity was operationally defined using a composite of Glasgow Coma Scale scores, structural imaging findings, and the …

Development And Preclinical Investigation Of Physically Cross-Linked And Ph-Sensitive Polymeric Gels As Potential Vaginal Contraceptives, Ankit K. Rochani, Vivek Agrahari, Neelima Chandra, Onkar N Singh, Timothy J Mccormick, Gustavo F Doncel, Meredith R Clark, Gagan Kaushal

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This study explored the development of cross-linked gels to potentially provide a physical barrier to vaginal sperm transport for contraception. Two types of gels were formulated, a physically cross-linked iota-carrageenan (Ci) phenylboronic acid functionalized hydroxylpropylmethyacrylate copolymer (PBA)-based (Ci-PBA) gel, designed to block vaginal sperm transport. The second gel was pH-shifting cross-linked Ci-polyvinyl alcohol-boric acid (Ci-PVA-BA) gel, designed to modulate its properties in forming a viscoelastic, weakly cross-linked transient network (due to Ci gelling properties) on vaginal application (at acidic pH of ~3.5-4.5) to a more elastic, densely cross-linked (due to borate-diol cross-linking) gel network at basic pH of 7-8 of …

Pharmacologic Ascorbic Acid As Early Therapy For Hospitalized Patients With Covid-19: A Randomized Clinical Trial, Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel A. Monti, Mark Levine

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic …

T-Cell Responses To Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses To The Colorectal Cancer Antigen, Guanylyl Cyclase C, John C. Flickinger, Jagmohan Singh, Yanki Yarman, Robert D Carlson, Joshua Barton, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Gram-positive bacterium Listeria monocytogenes (Lm) is an emerging platform for cancer immunotherapy. To date, over 30 clinical trials have been initiated testing Lm cancer vaccines across a wide variety of cancers, including lung, cervical, colorectal, and pancreatic. Here, we assessed the immunogenicity of an Lm vaccine against the colorectal tumor antigen GUCY2C (Lm-GUCY2C). Surprisingly, Lm-GUCY2C vaccination did not prime naïve GUCY2C-specific CD8+ T-cell responses towards the dominant H-2Kd-restricted epitope, GUCY2C254-262. However, Lm-GUCY2C produced robust CD8+ T-cell responses towards Lm-derived peptides suggesting that GUCY2C254-262 peptide may be subdominant to Lm-derived peptides. Indeed, incorporating immunogenic Lm peptides into an adenovirus-based GUCY2C …

A Prospective Cohort Study Of The Clinical Predictors Of Bacteremia In Under-Five Children With Acute Undifferentiated Fever Attending A Secondary Health Facility In Northwestern Nigeria, Taofik Oluwaseun Ogunkunle, Timothy Olanrewaju Adedoyin, Samuel Kolade Ernest, Fatimah Hassan-Hanga, Abdulazeez Imam, Rasaq Olaosebikan, Stephen K Obaro

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use.

Methods: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted …

Targeting Gastrointestinal Cancers With Chimeric Antigen Receptor (Car)-T Cell Therapy, Ross E Staudt, Robert D Carlson, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The immune system is capable of remarkably potent and specific efficacy against infectious diseases. For decades, investigators sought to leverage those characteristics to create immune-based therapies (immunotherapy) that might be far more effective and less toxic than conventional chemotherapy and radiation therapy for cancer. Those studies revealed many factors and mechanisms underlying the success or failure of cancer immunotherapy, leading to synthetic biology approaches, including CAR-T cell therapy. In this approach, patient T cells are genetically modified to express a chimeric antigen receptor (CAR) that converts T cells of any specificity into tumor-specific T cells that can be expanded to …

Spatial Metrics Of Interaction Between Cd163-Positive Macrophages And Cancer Cells And Progression-Free Survival In Chemo-Treated Breast Cancer, Brenton Maisel, Misung Yi, Amy R Peck, Yunguang Sun, Jeffrey A Hooke, Albert J Kovatich, Craig D Shriver, Hai Hu, Marja T Nevalainen, Takemi Tanaka, Nicole L Simone, Li Lily Wang, Hallgeir Rui, I Chervoneva

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor-associated macrophages (TAMs) promote progression of breast cancer and other solid malignancies via immunosuppressive, pro-angiogenic and pro-metastatic effects. Tumor-promoting TAMs tend to express M2-like macrophage markers, including CD163. Histopathological assessments suggest that the density of CD163-positive TAMs within the tumor microenvironment is associated with reduced efficacy of chemotherapy and unfavorable prognosis. However, previous analyses have required research-oriented pathologists to visually enumerate CD163+ TAMs, which is both laborious and subjective and hampers clinical implementation. Objective, operator-independent image analysis methods to quantify TAM-associated information are needed. In addition, since M2-like TAMs exert local effects on cancer cells through direct juxtacrine cell-to-cell interactions, …

The Concise Guide To Pharmacology 2021/22: Catalytic Receptors, Stephen Ph Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Adam J Pawson, Christopher Southan, Jamie A Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C Burnett, Richard W Farndale, Andreas Friebe, John Garthwaite, Adrian J Hobbs, Gavin E Jarvis, Michaela Kuhn, David Macewan, Tom P Monie, Andreas Papapetropoulos, Lincoln R Potter, Harald H H W Schmidt, Csaba Szabo, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will …

Level Of Utilization And Provider-Related Barriers To The Use Of Hydroxyurea In The Treatment Of Sickle Cell Disease Patients In Jos, North-Central Nigeria, Akinyemi O.D. Ofakunrin, Edache S. Okpe, Tolulope O. Afolaranmi, Rasaq Olaosebikan, Patience U. Kanhu, Kehinde Adekola, Nantok Dami, Atiene S. Sagay

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Hydroxyurea is underutilized by sickle cell health-care providers in Nigeria despite available evidence of its effectiveness in reducing the manifestations and complications of sickle cell disease (SCD).

Objectives: To assess the level of utilization and provider-related barriers to the use of hydroxyurea in SCD therapy in Jos, Nigeria.

Methods: A cross-sectional study conducted among 132 medical doctors providing care for SCD patients. Data on so- cio-demographics, utilization and barriers to hydroxyurea use were obtained. The barriers were fed cumulatively into the logistic regression model as predictors of utilization.

Results: Of the 132 care providers, 88 (67%) had been in …

Longitudinal Evaluation Of Azithromycin And Cytokine Concentrations In Amniotic Fluid Following One-Time Oral Dosing In Pregnancy., Rupsa C. Boelig, Edwin Lam, Ankit Rochani, Gagan Kaushal, Amanda Roman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

To utilize noninvasive collection of amniotic fluid in the setting of preterm premature rupture of membranes (PPROMs) to report the time concentration profile of azithromycin in amniotic fluid over 7 days from a single dose, and evaluate the correlation between azithromycin concentration and inflammatory markers in amniotic fluid. Prospective cohort study of five pregnant patients admitted with PPROMs and treated with a single 1 g oral azithromycin dose. Amniotic fluid was collected from pads and used to quantify azithromycin concentration as well as TNFa, IL-1a, IL-1b, IL-6, IL-8, and IL-10 concentrations. Primary outcome was time/concentration profile of azithromycin in amniotic …

Retinoids As Chemo-Preventive And Molecular-Targeted Anti-Cancer Therapies., Victoria O. Hunsu, Caroline O.B. Facey, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Retinoic acid (RA) agents possess anti‐tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving RARA occurs in acute promyelocytic leukemia (APL), and all‐trans …

Seeking Similarities Rather Than Differences With Adults To Aid In Therapeutic Advancement For Children., Mara L. Becker, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

No abstract provided.

Emerging Targets For The Diagnosis Of Parkinson's Disease: Examination Of Systemic Biomarkers., Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Parkinson's disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. …

Review Article: Diagnosis, Management And Patient Perspectives Of The Spectrum Of Constipation Disorders., Amol Sharma, Satish S C Rao, Kimberly Kearns, Kimberly D Orleck, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Chronic constipation is a common, heterogeneous disorder with multiple symptoms and pathophysiological mechanisms. Patients are often referred to a gastroenterology provider after laxatives fail. However, there is limited knowledge of the spectrum and management of constipation disorders.

AIM: To discuss the latest understanding of the spectrum of constipation disorders, tools for identifying a pathophysiologic-based diagnosis in the specialist setting, treatment options and the patient's perspective of constipation.

METHODS: Literature searches were conducted using PubMed for constipation diagnostic criteria, diagnostic tools and approved treatments. The authors provided insight from their own practices.

RESULTS: Clinical assessment, stool diaries and Rome IV …

A Randomized Trial To Improve Adherence To Follow-Up Eye Examinations Among People With Glaucoma, Benjamin E Leiby, Sarah E. Hegarty, Tingting Zhan, Jonathan S Myers, L Jay Katz, Julia A Haller, Michael Waisbourd, Christine Burns, Meskerem Divers, Jeanne Molineaux, Jeffrey Henderer, Charles Brodowski, Lisa A Hark

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments.

METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and …

Choline-Sigma-1r As An Additional Mechanism For Potentiation Of Orexin By Cocaine, Jeffrey Barr, Pingwei Zhao, G Cristina Brailoiu, Eugen Brailoiu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX₁ and OX₂, Gq-coupled GPCRs. We examined the effect of a selective OX₁ agonist, OXA (17-33) on cytosolic calcium concentration, [Ca²⁺ ]_i, in neurons of nucleus accumbens, an important area in the reward circuit. OXA (17-33) increased [Ca²⁺ ]_i in a dose-dependent manner; the effect was prevented by SB-334867, a selective OX₁ receptors antagonist. In Ca²⁺-free saline, the OXA (17-33)-induced increase in [Ca²⁺ ]_i was not affected by pretreatment …

Correlations Between Coffee Consumption And Metabolic Phenotypes, Plasma Folate, And Vitamin B12: Nhanes 2003 To 2006., Pratibha V Nerurkar, Krupa Gandhi, John J Chen

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

The Role Of Mirnas, Mirna Clusters, And Isomirs In Development Of Cancer Stem Cell Populations In Colorectal Cancer., Victoria A Stark, Caroline O B Facey, Vignesh Viswanathan, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss …

Epidemiology Of Covid-19 And Predictors Of Outcome In Nigeria: A Single-Center Study., Olayinka Rasheed Ibrahim, Bello Muhammed Suleiman, Suleiman Bello Abdullahi, Taofeek Oloyede, Abdallah Sanda, Maruf Sanusi Gbadamosi, Bashir Olajide Yusuf, Rabilu Yandoma Iliyasu, Lawal Magaji Ibrahim, Adamu Danladi Dawud, Sulaiman Saidu Bashir, Nwawueze Efam Okonta, Wasinda Francis Umar, Abiodun Gbenga Tekobo, Muhammadu Sani Abubakar, Bashir Taiye Aminu, Shuaibu Onoruoyiza Ibrahim, Rasaq Olaosebikan, Olugbenga Ayodeji Mokuolu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3-5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9-9.8).

Fatal Case Of Newborn Lassa Fever Virus Infection Mimicking Late Onset Neonatal Sepsis: A Case Report From Northern Nigeria, Taofik Oluwaseun Ogunkunle, Surajudeen Oyeleke Bello, Chinwe Immaculata Anderson, Rashida Musa, Rasaq Olaosebikan, Abdulazeez Imam

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Lassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis.

CASE PRESENTATION: The patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting …

Chimeric Ad5.F35 Vector Evades Anti-Adenovirus Serotype 5 Neutralization Opposing Gucy2c-Targeted Antitumor Immunity, John C. Flickinger, Jagmohan Singh, Robert D Carlson, Elinor Leong, Trevor R. Baybutt, Joshua Barton, Ellen M. Caparosa, Amanda M. Pattison, Jeff A. Rappaport, Jamin Roh, Tingting Zhan, Babar Bashir, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Adenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines. Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.

METHODS: Here, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) …

Mobilizing Toxins For Cancer Treatment: Historical Perspectives And Current Strategies., Jessica Kopenhaver, Robert D Carlson, Adam E Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...].