Digital Commons Network^™

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Low Yield Of Hepatitis C Infection In An Outreach Screening Program In Harris County, Texas, Hyun-Seok Kim, Rosalia Guerrero, Shane W Reader, Maria Daheri, Maya Balakrishnan, Catherine L Troisi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions.

Veterinarians’ Attitudes And Practices Regarding Opioid-Related Vet Shopping Practices In Tri-State Appalachian Counties: An Exploratory Study, Falguni C Patel, Jeffrey A Raines, Richard W Kim, Karen Gruszynski, Robert E Davis, Manoj Sharma, Gilbert Patterson, Jason W Johnson, Vinayak K Nahar

Faculty, Staff and Students Publications

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States.

RESULTS: …

Hypoxia-Inducible Factor (Hif)-2Α Reprograms Liver Macrophages To Protect Against Acute Liver Injury Via The Production Of Interleukin-6, Rachel Y Gao, Meng Wang, Qihui Liu, Dechun Feng, Yankai Wen, Yang Xia, Sean P Colgan, Holger K Eltzschig, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct hepatotoxicity of APAP triggers a cascade of innate immune responses that may exacerbate or limit the progression of tissue damage. A better understanding of this complex mechanism will help uncover targets for therapeutic interventions.

APPROACH AND RESULTS: We observed that …

Implementation Costs Of A Multi-Component Program To Increase Human Papillomavirus (Hpv) Vaccination In A Network Of Pediatric Clinics, Jarrod S. Eska, David R. Lairson, Lara S. Savas, Ross Shegog, C Mary Healy, Stanley W. Spinner Md, Maria E. Fernandez, Sally W. Vernon

Journal of Applied Research on Children: Informing Policy for Children at Risk

Introduction: HPV vaccination is both a clinically and cost-effective way to prevent HPV-related cancers. Increased focus on preventing HPV infection and HPV-related cancers has motivated development of strategies to increase adolescent vaccination rates. This analysis estimates the average cost associated with implementing programs aimed at increasing HPV vaccination from the perspective of the clinic decision makers. As providers and healthcare organizations consider vaccination initiatives, it is important for them to understand the costs associated with implementing these programs.

Methods: Healthcare provider assessment and feedback, reminders, and education; and parent education/reminder strategies were implemented in a large pediatric clinic network between …

Communication Strategies To Address Vaccine Hesitancy In Healthcare Settings And On Social Media, Lindy U. Mcgee Md, Jinny Suh Jd

Journal of Applied Research on Children: Informing Policy for Children at Risk

Abstract

Vaccine hesitancy is now recognized as a threat to global health. Its causes are complex, and it is defined by a resistance to or questioning of immunization. It is important to address vaccine hesitancy directly before people who are hesitant become vaccine refusers or anti-vaccine. Fortunately, with evidence-based information delivered with a compassionate communication style many of those who are hesitant to vaccinate can be persuaded to ultimately vaccinate. This paper aims to explain successful communication strategies used to address vaccine hesitancy in healthcare settings and on social media. Vaccine hesitant parents frequently list their child’s healthcare provider as …

Lessons From The Front Line: Advocating For Vaccine Policies At The Texas Capitol During Turbulent Times, Rekha Lakshmanan, Mha, Jason Sabo, Ma

Journal of Applied Research on Children: Informing Policy for Children at Risk

In 2003, anti-vaccine activists successfully advocated to change Texas law to make it easier for parents to send their children to public school without school required vaccinations. Over fifteen years ago, 2,314 non medical exemptions were filed. The Texas Department of State Health Services recently reported in the 2018-19 school year, 64,176 exemptions were submitted. As the number of non-medical exemptions increase, the risk for a vaccine preventable outbreak also increases.

Enacting strong immunization laws and policies, which includes improving access to vaccination, increasing education, and enhancing data collection, is cyclical. In the past ten years, over 17 pieces of …

Knowledge About The Human Papillomavirus Vaccine Among Employees At A Tertiary Cancer Center: Room For Improvement, Kristina R. Dahlstrom, Erich M. Sturgis, Ronald A. Depinho, Ernest Hawk, George P. Baum, Elenita Tamez, Rosalind S. Bello, Lori D. Stevens, Lois M. Ramondetta

Journal of Applied Research on Children: Informing Policy for Children at Risk

Introduction: The human papillomavirus (HPV) vaccine is recommended by the U.S. Centers for Disease Control and Prevention for routine vaccination of boys and girls to protect against HPV-related cancers and genital warts. To meet the Healthy People 2020 target for HPV vaccination, health care providers must understand the importance of strongly recommending the HPV vaccine to all eligible adolescents. We sought to determine HPV vaccination patterns among employees at a tertiary cancer center and their children and attitudes regarding HPV vaccination among the employees.

Methods: All employees at a tertiary cancer center were invited to participate in a cross-sectional survey …

Texas: Averting Disease And Confronting A New Vaccine Refusal Hierarchy, Susan Wootton, Peter J. Hotez, Julie Boom

Journal of Applied Research on Children: Informing Policy for Children at Risk

No abstract provided.

Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair

Dissertations and Theses (Open Access)

Integrins are known to play an important role in activating multiple intracellular pathways, one of which is focal adhesion kinase (FAK). Phosphorylation of FAK can lead to the activation of various downstream signaling pathways that can increase tumor cell growth and proliferation, making it an ideal target for cancer therapeutics. Due to the fact that many FAK inhibitors are limited in their penetration of the blood brain barrier, we investigated the use of Penfluridol, an antipsychotic drug known to attenuate integrin expression at a transcriptional level, in combination with oncolytic herpes simplex I virus (oHSV) in a glioblastoma model. We …

Maternal And Newborn Outcomes For Women Living With Hiv In Adapted Group Prenatal Care, Jodi Behr

Dissertations and Theses (Open Access)

Background: For women living with HIV (WLWH), managing HIV and their pregnancy can be challenging. WLWH have been identified at risk for lower adherence to prenatal care, increased maternal HIV Plasma RNA levels, decreased newborn gestational age, and newborn birth weight. Improved outcomes have been found with group prenatal care. Maternal and newborn outcomes for WLWH and their newborns in group prenatal care compared to WLWH and their newborns in individual care have not been evaluated.

Purpose: The aims of this study were to evaluate group differences between WLWH who attended individual prenatal care appointments (IC) compared to WLWH who …

An Assessment Of Outpatient Clinic Room Ventilation Systems And Possible Relationship To Disease Transmission, Kristin G. King

Dissertations and Theses (Open Access)

The delivery of healthcare in the United States is shifting from a largely inpatient model to an outpatient services model, but the physical infrastructure for outpatient clinics or medical offices may not be as robust as inpatient hospitals regarding whole room ventilation requirements. Guidelines for the design of healthcare facilities and national standards for ventilation establish generally acceptable ventilation rates for outpatient clinics, but it is unclear if these standards are actually being integrated into these settings. Published peer reviewed literature indicates that inadequate ventilation rates can be a risk factor in airborne transmission of infectious diseases in outpatient clinics, …

Understanding Factors That Impact Health Behaviors And Access To Healthcare Among Youth Experiencing Homelessness, Kathryn Rosales Gallardo

Dissertations and Theses (Open Access)

Youth experiencing homelessness (YEH) have a high risk of adverse health outcomes and their utilization of healthcare services is low. This dissertation aims to further understand factors that impact YEH’s health behaviors and access to healthcare services. This dissertation is in the form of three manuscripts that each contribute to the overall aim. In manuscript 1, we examined the rates and correlates of human papillomavirus (HPV) vaccination initiation and completion among a sample of YEH in seven U.S. cities using logistic regression models. We found that HPV vaccination completion is low among male (19%) and female (37%) YEH. Among male …

Trends In Injection Drug Use In Texas Treatment Facility Admissions, Cara Dahlhausen

Dissertations and Theses (Open Access)

This is a serial cross-sectional secondary analysis of drug treatment admissions records from the TEDS-A from years 2013-2017. The prevalence of injected drug use was calculated for each year and analyzed across the five-year period using a chi-square test to determine the presence of significant change in injection drug use from 2013 to 2017. Prevalence of injection drug use also will be calculated for each year by drug type (heroin, methamphetamine, and cocaine), age, sex, ethnicity and race, and will be analyzed for trends using a chi-square test.

Exploration Of Breastfeeding As A Protective Factor For Breast Cancer In South African Women: A Nested Case-Control Study, Booker S. Quiera

Dissertations and Theses (Open Access)

Background. South African’s (SA) breast cancer incidence rate is continually increasing (39 per 100,000 (2012) versus 46.2 per 100,000 (2018) with trends towards later-stage diagnosis. In previous literature, breastfeeding has been assessed as a protective factor for breast cancer; however, the SA population experiences inconsistent breastfeeding trends, rates, and support services. Therefore, this study will evaluate the inverse association between breast cancer and breastfeeding history. Methods. Cases (breast cancer) and controls (mastalgia) were matched 1:1 on clinical visit from May-August 2019 at Groote Schuur Hospital (GSH) in Cape Town, Western Cape, South Africa. Breastfeeding history, breast carcinoma diagnosis, and clinically …

Exploration Of Breastfeeding As A Protective Factor For Breast Cancer In South African Women: A Nested Case-Control Study, Quiera S. Booker

Dissertations and Theses (Open Access)

South African’s (SA) breast cancer incidence rate is continually increasing (39 per 100,000 (2012) versus 46.2 per 100,000 (2018) with trends towards later-stage diagnosis. In previous literature, breastfeeding has been assessed as a protective factor for breast cancer; however, the SA population experiences inconsistent breastfeeding trends, rates, and support services. Therefore, this study will evaluate the inverse association between breast cancer and breastfeeding history. Methods. Cases (breast cancer) and controls (mastalgia) were matched 1:1 on clinical visit from May-August 2019 at Groote Schuur Hospital (GSH) in Cape Town, Western Cape, South Africa. Breastfeeding history, breast carcinoma diagnosis, and clinically relevant …

Vestigial-Like 1 Is A Shared Targetable Cancer-Placenta Antigen Expressed By Pancreatic And Basal-Like Breast Cancers, Sherille Denae Bradley

Dissertations and Theses (Open Access)

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regression by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from tumors of PDAC patients. This led to the identification of a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1), a novel putative TAA demonstrating overexpression in multiple tumor types and low or absent transcript expression in normal tissues with the exception of placenta. VGLL1-specific CTL isolated and expanded from the blood of a male PDAC patient …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Loss Of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head And Neck Squamous Carcinoma To Radiation Through Induction Of Necroptosis., Burak Uzunparmak

Dissertations and Theses (Open Access)

Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T Melia, Armando Paez, Gail Reid, Lisa M Chirch, Vera P Luther, Brian G Blackburn, Federico Perez, Emily Abdoler, Daniel R Kaul, Susan Rehm, Nada Harik, Alice Barsoumian, Anna K Person, Heather Yun, J David Beckham, Susan Boruchoff, Paloma F Cariello, James B Cutrell, Christopher J Graber, Dong Heun Lee, Eileen Maziarz, Molly L Paras, Raymund R Razonable, Roseanne Ressner, Anne Chen, Brian Chow, Gerome Escota, Erica Herc, Andrew Johnson, Ryan C Maves, Obinna Nnedu, Heather Clauss, Prathit Kulkarni, Paul S Pottinger, Jose A Serpa, Tanaya Bhowmick, Marvin Bittner, Darcy Wooten, Beata Casanas, Rachel Shnekendorf, Emily A Blumberg

Faculty, Staff and Students Publications

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …

Pesticides Decrease Bacterial Diversity And Abundance Of Irrigated Rice Fields, Michael Onwona-Kwakye, Kimberly Plants-Paris, Kadiatou Keita, Jessica Lee, Paul J Van Den Brink, Jonathan N Hogarh, Charles Darkoh

Faculty, Staff and Student Publications

Bacteria play an important role in soil ecosystems and their activities are crucial in nutrient composition and recycling. Pesticides are extensively used in agriculture to control pests and improve yield. However, increased use of pesticides on agricultural lands results in soil contamination, which could have adverse effect on its bacterial communities. Here, we investigated the effect of pesticides commonly used on irrigated rice fields on bacterial abundance and diversity. Irrigated soil samples collected from unexposed, pesticide-exposed, and residual exposure areas were cultured under aerobic and anaerobic conditions. DNA was extracted and analysed by 16S rRNA sequencing. The results showed overall …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

A Broad-Spectrum Antiviral Molecule, Ql47, Selectively Inhibits Eukaryotic Translation, Mélissanne De Wispelaere, Margot Carocci, Dominique J Burri, William J Neidermyer, Calla M Olson, Imme Roggenbach, Yanke Liang, Jinhua Wang, Sean P J Whelan, Nathanael S Gray, Priscilla L Yang

Faculty, Staff and Students Publications

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the …

Safety And Immunogenicity Of The Oral, Inactivated, Enterotoxigenic Escherichia Coli Vaccine Etvax In Bangladeshi Children And Infants: A Double-Blind, Randomised, Placebo-Controlled Phase 1/2 Trial, Firdausi Qadri, Marjahan Akhtar, Taufiqur R Bhuiyan, Mohiul I Chowdhury, Tasnuva Ahmed, Tanzeem A Rafique, Arifuzzaman Khan, Sadia I A Rahman, Farhana Khanam, Anna Lundgren, Gudrun Wiklund, Joanna Kaim, Madeleine Löfstrand, Nils Carlin, A Louis Bourgeois, Nicole Maier, Alan Fix, Thomas Wierzba, Richard I Walker, Ann-Mari Svennerholm

Faculty and Staff Publications

Background: Enterotoxigenic Escherichia coli causes diarrhoea, leading to substantial mortality and morbidity in children, but no specific vaccine exists. This trial tested an oral, inactivated, enterotoxigenic E coli vaccine (ETVAX), which has been previously shown to be safe and highly immuongenic in Swedish and Bangladeshi adults. We tested the safety and immunogenicity of ETVAX, consisting of four E coli strains overexpressing the most prevalent colonisation factors (CFA/I, CS3, CS5, and CS6) and a toxoid (LCTBA) administered with or without a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant, in Bangladeshi children.

Methods: We did a randomised, double-blind, placebo-controlled, dose-escalation, age-descending, phase …