Digital Commons Network^™

One Size Does Not Fit All: Advanced Practice Provider Considerations For The Antimicrobial Steward., Kyleen E. Swords, Gina Weddle, Joshua C. Herigon, Paula D. Stering, Matthew S L Lee

Manuscripts, Articles, Book Chapters and Other Papers

Advanced practice providers are a diverse and established group of antimicrobial prescribers in both ambulatory and inpatient settings. We outline important considerations for antimicrobial stewardship programs and stewards to consider when engaging this important group of providers.

Systematic Design And Data-Driven Evaluation Of Social Determinants Of Health Ontology (Sdoho), Yifang Dang, Fang Li, Xinyue Hu, Vipina K Keloth, Meng Zhang, Sunyang Fu, Muhammad F Amith, J Wilfred Fan, Jingcheng Du, Evan Yu, Hongfang Liu, Xiaoqian Jiang, Hua Xu, Cui Tao

Faculty, Staff and Student Publications

Objective: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way.

Material and methods: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and …

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J Hultgren, Jennifer N Walker, Ritwij Kulkarni

Faculty, Staff and Student Publications

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in sucD and fumC (tricarboxylic acid …

Dynamics Of Anti-Influenza Mucosal Iga Over A Season In A Cohort Of Individuals Living Or Working In A Long-Term Care Facility, Matt D T Hitchings, Brooke A Borgert, Adam Shir, Bingyi Yang, Kyra H Grantz, Jacob Ball, Carlos A Moreno, Kenneth Rand, Parker A Small, Keith R Fowke, Derek A T Cummings

Faculty, Staff and Student Publications

BACKGROUND: Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited.

METHODS: We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples.

RESULTS: Overall, 28.2% and 11.3% of individuals experienced a 2-fold and …

Class-Driven Synergy And Antagonism Between A Pseudomonas Phage And Antibiotics, Paul Nicholls, Justin R Clark, Carmen Gu Liu, Austen Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge. Bacteriophages have evolved to prey on these biofilms over millions of years, using hydrolases and depolymerases to penetrate biofilms and reach cellular targets. Here, we assessed how a newly discovered KMV-like phage (ΦJB10) interacts with antibiotics to treat P. aeruginosa more effectively in both planktonic and biofilm forms. By testing representatives of four classes of antibiotics (cephalosporins, aminoglycosides, fluoroquinolones, and carbapenems), we demonstrated …

Immunological Monitoring In Hepatitis C Virus Controlled Human Infection Model, Naglaa H Shoukry, Andrea L Cox, Christopher M Walker

Faculty, Staff and Student Publications

Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C virus and how such responses are modified by vaccination. In this article, we discuss the approach to immunological monitoring during such trials, including a set of recommendations for optimal sampling schedule and preferred immunological assays to examine the different arms of the immune response. We recommend that this approach be adapted to different trial designs. Finally, we discuss how these studies can provide surrogate predictors of the success of candidate vaccines.

Predicting Pediatric Tuberculosis: The Need For Age-Specific Host Biosignatures, Sara Suliman, Devan Jaganath, Andrew Dinardo

Faculty, Staff and Students Publications

No abstract provided.

Hepatitis A Virus And Hepatitis E Virus As Food- And Waterborne Pathogens—Transmission Routes And Methods For Detection In Food, Katalin Nemes, Sofia Persson, Magnus Simonsson

Faculty, Staff and Student Publications

Foodborne viruses are an important threat to food safety and public health. Globally, there are approximately 5 million cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) every year. HAV is responsible for numerous food-related viral outbreaks worldwide, while HEV is an emerging pathogen with a global health burden. The reported HEV cases in Europe have increased tenfold in the last 20 years due to its zoonotic transmission through the consumption of infected meat or meat products. HEV is considered the most common cause of acute viral hepatitis worldwide currently. This review focuses …

Prevalence Of Symptoms ≤12 Months After Acute Illness, By Covid-19 Testing Status Among Adults — United States, December 2020–March 2023, Juan Carlos C Montoy, James Ford, Huihui Yu, Michael Gottlieb, Dana Morse, Michelle Santangelo, Kelli N O'Laughlin, Kevin Schaeffer, Pamela Logan, Kristin Rising, Mandy J Hill, Lauren E Wisk, Wafah Salah, Ahamed H Idris, Ryan M Huebinger, Erica S Spatz, Robert M Rodriguez, Robin E Klabbers, Kristyn Gatling, Ralph C Wang, Joann G Elmore, Samuel A Mcdonald, Kari A Stephens, Robert A Weinstein, Arjun K Venkatesh, Sharon Saydah, Innovative Support For Patients With Sars-Cov-2 Infections Registry (Inspire) Group

Faculty, Staff and Student Publications

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline …

A Multicenter, Controlled Human Infection Study Of Influenza A(H1n1)Pdm09 In Healthy Adults, Justin R Ortiz, David I Bernstein, Daniel F Hoft, Christopher W Woods, Micah T Mcclain, Sharon E Frey, Rebecca C Brady, Christopher Bryant, Ashley Wegel, Robert W Frenck, Emmanuel B Walter, Getahun Abate, Sarah R Williams, Robert L Atmar, Wendy A Keitel, Nadine Rouphael, Mathew J Memoli, Mamodikoe K Makhene, Paul C Roberts, Kathleen M Neuzil

Faculty, Staff and Students Publications

BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study.

METHODS: We inoculated unvaccinated healthy adults aged 18-49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding.

RESULTS: Of 76 …

Unknown Rectal Lesions: A Case Of Severe Proctitis Secondary To Mpox In The Setting Of Concomitant Hiv, Syphilis, Hsv, And Chlamydia, Nicole Robertson Mph, James Crosby Do, Cynthia R. Young Md, Msc, Anne E. Sayers Md, Nicholas J. Van Sickles Md

ePublications of Emerging Medical Research Scholars

Introduction:

Mpox emerged as a public health crisis with limited research describing co-occurring HIV and sexually transmitted infections (STIs). We present a case of severe proctitis secondary to Mpox with concomitant HIV (Human Immunodeficiency Virus), syphilis, HSV (Herpes Simplex Virus), and chlamydia and review presentation, diagnosis, treatment, and prevention of Mpox with concurrent STIs.

Case Presentation:

34-year-old male living with HIV (LWH) presenting with worsening rectal pain, multiple anal papules, and fever. His laboratory workup revealed simultaneous positive results for orthopoxvirus, chlamydia, and HSV-1 PCR. We initiated tecovirimat due to rectal involvement and uncontrolled pain. He subsequently developed lesions on …

Under One Roof – An Integrated Clinic For Substance Use Disorder And Viral Hepatitis/Hiv Treatment, Sarah Hipkens, Emily Caron, Wendy Craig, Kinna Thakarar

Journal of Maine Medical Center

Introduction: Integration of viral hepatitis/HIV care and substance use disorder (SUD) treatment has been shown to improve patient outcomes, but data are lacking in rural states like Maine. Our study objective was to assess the baseline characteristics and outcomes of patients with SUD who receive combined substance use and viral hepatitis/HIV treatment at a recently established “Bridge Program” in our rural state.

Methods: We conducted a retrospective chart review of patients enrolled in the Bridge Program between January 2020 and November 2021. We then performed a descriptive analysis of demographics, health characteristics, preventive services, and treatment outcomes.

Results: A total …

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini

Faculty, Staff and Student Publications

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior …

Traf3-Ewsr1 Signaling Axis Acts As A Checkpoint On Germinal Center Responses, Yanchuan Li, Lele Zhu, Chun-Jung Ko, Jin-Young Yang, Hongjiao Wang, Ganiraju Manyam, Jing Wang, Xuhong Cheng, Shuli Zhao, Zuliang Jie

Faculty, Staff and Student Publications

The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B …

Dna-Encoded Chemical Libraries Yield Non-Covalent And Non-Peptidic Sars-Cov-2 Main Protease Inhibitors, Ravikumar Jimmidi, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Peng-Jen Chen, Kurt M Bohren, Seyed Arad Moghadasi, Leroy Versteeg, Christina Nnabuife, Jian-Yuan Li, Xuan Qin, Ying-Chu Chen, John C Faver, Pranavanand Nyshadham, Kiran L Sharma, Banumathi Sankaran, Allison Judge, Zhifeng Yu, Feng Li, Jeroen Pollet, Reuben S Harris, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that …

Transmission Of Yellow Fever Vaccine Virus Through Blood Transfusion And Organ Transplantation In The Usa In 2021: Report Of An Investigation, Carolyn V. Gould, Rebecca J. Free, Julu Bhatnagar, Raymond A. Soto, Tricia L. Royer, Warren R. Maley, Sean Moss, Matthew A. Berk, Rebecca Craig-Shapiro, Rosy Priya L. Kodiyanplakkal, Lars F. Westblade, Thangamani Muthukumar, Yoram A. Puius, Amresh Raina, Azam Hadi, Kymberly A. Gyure, Danielle Trief, Marcus Pereira, Matthew J. Kuehnert, Vennus Ballen, Debra A. Kessler, Kimberly Dailey, Charles Omura, Thuy Doan, Steve Miller, Michael R. Wilson, Jennifer A. Lehman, Jana M. Ritter, Elizabeth Lee, Luciana Silva-Flannery, Sarah Reagan-Steiner, Jason O. Velez, Janeen J. Laven, Kelly A. Fitzpatrick, Amanda Panella, Emily H. Davis, Holly R. Hughes, Aaron C. Brault, Kirsten St George, Amy B. Dean, Joel Ackelsberg, Sridhar V. Basavaraju, Charles Y. Chiu, J. Erin Staples

Department of Medicine Faculty Papers

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients.

METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by …

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Donor-Recipient Specificity And Age-Dependency In Fecal Microbiota Therapy And Probiotic Resolution Of Gastrointestinal Symptoms, Qinglong Wu, Prapaporn Boonma, Shyam Badu, Nazli Yalcinkaya, Sik Yu So, Kevin W Garey, Kent Williams, L Eugene Arnold, Robert J Shulman, Richard Kellermayer, Tor C Savidge

Faculty, Staff and Students Publications

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal …

The Effects Of Covid-19 On Cognition In The Pediatric Population, Mia Ramirez, Hope Mccarroll, Lisa Griggs-Stapleton

Summer 2023 Virtual OTD Capstone Symposium

Coronavirus disease or COVID-19, is an infectious disease caused by the SARS-CoV-2 virus. COVID-19 can affect adults and children by causing long-term symptoms such as difficulty concentrating, anxiety, depression, long-term breathing problems, and even heart complications. Children represent about 19% of all reported COVID-19 cases since the pandemic first began. Children also can have trouble concentrating, which can impact their ability to attend school and do their daily activities that require concentration, such as dressing, showering, and social participation. Cognitive deficits due to COVID-19 can impact the pediatric population as they may have decreased occupational performance in desired occupations, such …

Effects Of Preoperative Chlorhexidine Gluconate (Chg) Cloths Educational Intervention For Preoperative Staff On Chg Knowledge And Surgical Site Infection Rates: A Quality Improvement Initiative., Deven Leffler

Doctor of Nursing Practice Papers

Abstract

Background: Surgical site infections (SSIs) are the most common cause of a surgical complication and account for 38% of all hospital acquired infections (HAI). The cost of caring for SSIs in the United States can range from $3.5-$10 billion annually.

Purpose: The purpose of this DNP Quality Improvement (QI) initiative was to improve preoperative staff’s knowledge and application of the Food and Drug Administration (FDA) approved 3-minute application scrub time for the 2% CHG cloths and reduce SSIs for an acute care hospital located in Louisville, Kentucky.

Methods: Quality improvement was initiated using the Plan, Do, Study, Act (PDSA) …

Ultrastructure For The Diagnosis Of Primary Ciliary Dyskinesia In South Africa, A Resource-Limited Setting, Monica Birkhead, Samuel Otido, Theodore Mabaso, Keketso Mopeli, Dorcas Tlhapi, Charl Verwey, Ziyaad Dangor

Paediatrics and Child Health, East Africa

Introduction: International guidelines recommend a multi-faceted approach for successful diagnoses of primary ciliary dyskinesia (PCD). In the absence of a gold standard test, a combination of genetic testing/microscopic analysis of structure and function/nasal nitric oxide measurement is used. In resourcelimited settings, often none of the above tests are available, and in South Africa, only transmission electron microscopy (TEM) is available in central anatomical pathology departments. The aim of this study was to describe the clinical and ultrastructural findings of suspected PCD cases managed by pediatric pulmonologists at a tertiary-level state funded hospital in Johannesburg.

Methods: Nasal brushings were …

Role Of Hospital Leadership In Pandemic Preparedness: Experience At A Tertiary Hospital In Kenya During The Covid-19 Pandemic, Lucy Mwangi, William Macharia, Benjamin Wachira, Jemimah Kimeu, Boniface Mativa, Lukoye Atwoli

Paediatrics and Child Health, East Africa

Introduction: Pandemic preparedness refers to being ready for, responding to and recovering from public health crises, and is integral for health security. Hospital leadership is a critical building block of an effective healthcare system, providing policy, accountability and stewardship in a health crisis.

Objectives and methods: We aimed to describe the leadership and governance structures put in place at the Aga Khan University Hospital, Nairobi, a private not-forprofit tertiary healthcare facility, following the COVID-19 pandemic. We reviewed over 200 hospital documents archived in the COVID-19 repository including those received from the Kenya Ministry of Health, emails, memos, bulletins, meeting minutes, …

Who O2cov2: Oxygen Requirements And Respiratory Support In Patients With Covid-19 In Low-And-Middle Income Countries—Protocol For A Multicountry, Prospective, Observational Cohort Study, Pryanka Relan, Srinivas Murthy, John Marshall, Djillali Annane, Sylvie Chevret, Yaseen Arabi, Wangari Siika, Sara Dominguez Rodriguez, Pauline Convocar, Janet Diaz

Anaesthesiology, East Africa

Introduction: SARS-CoV-2 has been identified as the cause of the disease officially named COVID-19, primarily a respiratory illness. COVID-19 was characterised as a pandemic on 11 March 2020. It has been estimated that approximately 20% of people with COVID-19 require oxygen therapy. Oxygen has been listed on the WHO Model List of Essential Medicines List and Essential Medicines List for Children for almost two decades. The COVID-19 pandemic has highlighted, more than ever, the acute need for scale-up of oxygen therapy. Detailed data on the use of oxygen therapy in low-and-middle income countries at the patient and facility level are …

Infants Admitted To Us Intensive Care Units For Rsv Infection During The 2022 Seasonal Peak., Natasha Halasa, Laura D. Zambrano, Justin Z. Amarin, Laura S. Stewart, Margaret M. Newhams, Emily R. Levy, Steven L. Shein, Christopher L. Carroll, Julie C. Fitzgerald, Marian G. Michaels, Katherine Bline, Melissa L. Cullimore, Laura Loftis, Vicki L. Montgomery, Asumthia S. Jeyapalan, Pia S. Pannaraj, Adam J. Schwarz, Natalie Z. Cvijanovich, Matt S. Zinter, Aline B. Maddux, Melania M. Bembea, Katherine Irby, Danielle M. Zerr, Joseph D. Kuebler, Christopher J. Babbitt, Mary Glas Gaspers, Ryan A. Nofziger, Michele Kong, Bria M. Coates, Jennifer E. Schuster, Shira J. Gertz, Elizabeth H. Mack, Benjamin R. White, Helen Harvey, Charlotte V. Hobbs, Heda Dapul, Andrew D. Butler, Tamara T. Bradford, Courtney M. Rowan, Kari Wellnitz, Mary Allen Staat, Cassyanne L. Aguiar, Saul R. Hymes, Adrienne G. Randolph, Angela P. Campbell, Rsv-Pic Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.

EXPOSURE: Respiratory syncytial virus.

MAIN OUTCOMES AND MEASURES: Data were captured on demographics, …

Identification Of Immunodominant T Cell Epitopes Induced By Natural Zika Virus Infection, Christopher S. Eickhoff, Krystal A. Meza, Frances E. Terry, Chase G. Colbert, Azra Blazevic, Andres H. Gutiérrez, E. Taylor Stone, James D. Brien, Amelia K. Pinto, Hana M. El Sahly, Mark J. Mulligan, Nadine Rouphael, Maria L. Alcaide, Kay M. Tomashek, Chris Focht, William D. Martin, Leonard Moise, Anne S. De Groot, Daniel F. Hoft

Markey Cancer Center Faculty Publications

Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which …

The Role Of Vaccination Route With An Adenovirus-Vectored Vaccine In Protection, Viral Control, And Transmission In The Sars-Cov-2/K18-Hace2 Mouse Infection Model, Alexandria Dickson, Elizabeth Geerling, E. Taylor Stone, Mariah Hassert, Tara L. Steffen, Taneesh Makkena, Madeleine Smither, Katherine E. Schwetye, Jianfeng Zhang, Bertrand Georges, M. Scot Roberts, John J. Suschak, Amelia K. Pinto, James D. Brien

Markey Cancer Center Faculty Publications

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed …

Development, Roll-Out And Implementation Of An Antimicrobial Resistance Training Curriculum Harmonizes Delivery Of In-Service Training To Healthcare Workers In Kenya, Josiah Njeru, Joshua Odero, Sheilla Chebore, Mungai Ndung’U, Emmanuel Tanui, Evelyn Wesangula, Romona Ndanyi, Susan Githii, R Gunturu, Willy Mwangi

Pathology, East Africa

Background: Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.

Methods: An initial stakeholders’ forum was convened to …

Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites In Treg-Deficient Scurfy Mice, Yuying Liu, Shabba A Armbrister, Beanna Okeugo, Tingting W Mills, Rhea C Daniel, Jee-Hwan Oh, Jan-Peter Van Pijkeren, Evelyn S Park, Zeina M Saleh, Sharmistha Lahiri, Stefan Roos, Jmarc Rhoads

Faculty, Staff and Student Publications

Probiotic Limosilactobacillus reuteri DSM 17938 (DSM 17938) prolongs the survival of Treg-deficient scurfy (SF) mice and reduces multiorgan inflammation by a process requiring adenosine receptor 2A (A2A) on T cells. We hypothesized that L. reuteri-derived ecto-5'-nucleotidase (ecto-5'NT) activity acts to generate adenosine, which may be a central mediator for L. reuteri protection in SF mice. We evaluated DSM 17938-5'NT activity and the associated adenosine and inosine levels in plasma, gut, and liver of SF mice. We examined orally fed DSM 17938, DSM 17938Δ5NT (with a deleted 5'NT gene), and DSM 32846 (BG-R46) (a naturally selected strain derived from DSM 17938). …

Predicting Severity Of Radiation Induced Lymphopenia In Individual Proton Therapy Patients For Varying Dose Rate And Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations, Lucas Mccullum, Jungwook Shin, Stella Xing, Chris Beekman, Jan Schuemann, Theodore Hong, Dan Duda, Radhe Mohan, Steven H Lin, Camilo M Correa-Alfonso, Sean Domal, Julia Withrow, Wesley Bolch, Harald Paganetti, Clemens Grassberger

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters.

METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute …

Low-Grade Intestinal Inflammation Two Decades After Pelvic Radiotherapy, Sravani Devarakonda, Annika Thorsell, Per Hedenström, Azar Rezapour, Lisen Heden, Sanghita Banerjee, Malin E V Johansson, George Birchenough, Amelie Toft Morén, Karin Gustavsson, Viktor Skokic, Victor L Pettersson, Fei Sjöberg, Marie Kalm, Mohammad Al Masri, Michaela Ekh, Henrik Fagman, Mats Wolving, Rosie Perkins, Rodrigo A Morales, Francisca Castillo, Eduardo J Villablanca, Ulf Yrlid, Karin Bergmark, Gunnar Steineck, Cecilia Bull

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.

METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag …