Medical Immunology Commons^™

Management Of Extracorporeal Membrane Oxygenation Anticoagulation In The Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Ariane Willems, Marc M Anders, Alejandro V Garcia, Adam M Vogel, Andrew R Yates, Jennifer A Muszynski, Peta M A Alexander, Katherine Steffen, Sitaram Emani, Alison Gehred, Elizabeth Lyman, Lakshmi Raman

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference.

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed …

Priorities For Clinical Research In Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Jennifer A Muszynski, Melania M Bembea, Alison Gehred, Elizabeth Lyman, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Peta M A Alexander

Faculty, Staff and Students Publications

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus.

DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children.

DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third …

Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation In Melanoma: Impact Of Antibiotic Preconditioning On Microbiome And Immunity, Isabella C Glitza, Yongwoo David Seo, Christine N Spencer, Jennifer R Wortman, Elizabeth M Burton, Farah A Alayli, Christopher P Loo, Shikha Gautam, Ashish Damania, Julie Densmore, Justin Fairchild, Christopher R Cabanski, Matthew C Wong, Christine B Peterson, Brian Weiner, Nathan Hicks, John Aunins, Christopher Mcchalicher, Emily Walsh, Michael T Tetzlaff, Omid Hamid, Patrick A Ott, Genevieve M Boland, Ryan J Sullivan, Kenneth F Grossmann, Nadim J Ajami, Theresa Lavallee, Matthew R Henn, Hussein A Tawbi, Jennifer A Wargo

Faculty, Staff and Student Publications

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an overall response rate …

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative (Peace) Consensus Conference, Peta M A Alexander, Melania M Bembea, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed S Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Christopher Almond, Marc M Anders, Gail M Annich, Leonardo R Brandão, Wayne Chandler, Megan Delaney, Robert Digeronimo, Sitaram Emani, Samir K Gadepalli, Alejandro V Garcia, Bereketeab Haileselassie, Robert Hyslop, Martin C J Kneyber, Lisa Baumann Kreuziger, Jennifer Le, Laura Loftis, Ali B V Mcmichael, D Michael Mcmullan, Paul Monagle, Kathleen Nicol, Matthew L Paden, Jason Patregnani, John Priest, Leslie Raffini, Lindsay M Ryerson, Steven R Sloan, Jun Teruya, Andrew R Yates, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.

DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any …

Agapanthus Allergic Contact Dermatitis: A Case Report, Yasuhiro Horiuchi

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Agapanthus (Lily of the Nile) is a genus in the flowering plant family Amaryllidaceae. Contact dermatitis caused by flowering plants is common, but there are no reports of contact dermatitis caused by this plant, Agapanthus.

Case Illustration: An 82-year-old Japanese man had cultivated Agapanthus in his home garden. After breaking the stem of the leaf while wearing shorts, he noticed erythematous rashes on the thighs. The patch test of the leaf stem sap “as is” showed mildly positive, with erythematous papules.

Discussion: The patch test confirmed the allergic contact dermatitis of Agapanthus with leaf stem sap. There are many …

Innate And Adaptive Immune Responses That Control Lymph-Borne Viruses In The Draining Lymph Node, Carolina R. Melo-Silva, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

The interstitial fluids in tissues are constantly drained into the lymph nodes (LNs) as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics. LNs are strategically positioned and have the appropriate cellular composition to serve as sites of adaptive immune initiation against invading pathogens. However, for lymph-borne viruses, which disseminate from the entry site to other tissues through the lymphatic system, immune cells in the draining LN (dLN) also play critical roles in curbing systemic viral dissemination during primary and secondary infections. Lymph-borne viruses in tissues can be transported to dLNs as free virions in …

Antidepressant Effect Of Enzymatic Porcine Placenta Hydrolysate In Repeated Immobilization Stress-Induced Ovariectomized Female Mice, Minsook Ye, Sharon Nguyen, Min Ju Kim, Jee Sun Hwang, Gun Won Bae, Keun-Hang Susan Yang, Insop Shim

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic …

Protein Nanoparticles As Vaccine Platforms For Human And Zoonotic Viruses, Kush Kumar Pandey, Bikash R. Sahoo, Asit K. Pattnaik

Nebraska Center for Virology: Faculty Publications

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or liveattenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective …

Clonality And Epidemiological Studies Of E. Coli Strain Collected From Abu Dhabi Emirate Using Ngs And Bioinformatic Tools, Ahmed Abdelrahman Mohamed

Theses

In the current landscape, where antibiotic resistance in bacteria is steadily rising, the role of bacterial genomics has assumed increasing significance. Therefore, it is necessary for microbiologists to acquire proficiency in the utilization of these methods and tools to harness their potential in gaining valuable insights into bacterial genomes. This can facilitate the development of innovative strategies for managing and treating bacterial infections. Here we present the power of the whole-genome sequencing technology in characterization of multidrug resistant Escherichia coli isolates. Fourteen Escherichia coli isolates were selected for this study. Following the standard microbiological techniques to confirm the sample identification, …

Preparing Patients For Oral Immunotherapy (Ppoint): International Delphi Consensus For Procedural Preparation And Consent, Douglas P Mack, Timothy E Dribin, Paul J Turner, Richard L Wasserman, Mariam A Hanna, Marcus Shaker, Mimi L K Tang, Pablo Rodríguez Del Río, Brad Sobolewski, Elissa M Abrams, Aikaterini Anagnostou, Stefania Arasi, Sakina Bajowala, Philippe Bégin, Scott B Cameron, Edmond S Chan, Sharon Chinthrajah, Andrew T Clark, Paul Detjen, George Du Toit, Motohiro Ebisawa, Arnon Elizur, Jeffrey M Factor, Justin Greiwe, Jonathan O'B Hourihane, Sarah W Hughes, Douglas H Jones, Antonella Muraro, Anna Nowak-Wegrzyn, Nandinee B Patel, Amy M Scurlock, Atul N Shah, Sayantani B Sindher, Stephen Tilles, Brian P Vickery, Julie Wang, Hugh H Windom, Matthew Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process.

OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form.

METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was …

Bacillary Angiomatosis In A Patient With Hiv And Disseminated Mycobacterium Avium Complex Infection, Ibeth P Caceres, Angelique Ruml, Rubi Montejano, Omid Jalali, Theodore Rosen

Faculty, Staff and Students Publications

Bartonella is a genus of arthropod-borne bacterial pathogens that typically cause persistent infections of erythrocytes and endothelial cells in mammalian hosts. The species that primarily infect humans are Bartonella henselae and Bartonella quintana. Depending on immune status, the clinical presentation of B. henselae may differ, manifesting as cat-scratch disease in immunocompetent individuals or bacillary angiomatosis (BA) and peliosis in immunocompromised patients. The cutaneous manifestations of BA are typically characterized by occasionally painful, angiomatous papules and nodules, often with a chronic, persistent course. Herein, we present a case of biopsy-confirmed B. henselae infection in a 32-year-old HIV-positive female with acquired immunodeficiency …

Reversible Male Contraception By Targeted Inhibition Of Serine/Threonine Kinase 33, Angela F Ku, Kiran L Sharma, Hai Minh Ta, Courtney M Sutton, Kurt M Bohren, Yong Wang, Srinivas Chamakuri, Ruihong Chen, John M Hakenjos, Ravikumar Jimmidi, Katarzyna Kent, Feng Li, Jian-Yuan Li, Lang Ma, Chandrashekhar Madasu, Murugesan Palaniappan, Stephen S Palmer, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Yasmin M Vasquez, Jian Wang, Jennifer Wilkinson, Zhifeng Yu, Qiuji Ye, Damian W Young, Mingxing Teng, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that …

Viral Reprogramming Of Host Transcription Initiation, Nathan A. Ungerleider, Claire Roberts, Tina M. O’Grady, Trang T. Nguyen, Melody Baddoo, Jia Wang, Eman Ishaq, Monica Concha, Meggie Lam, Jordan Bass, Truong D. Nguyen, Nick Van Otterloo, Nadeeshika Wickramarachchige-Dona, Dorota Wyczechowska, Maria Morales, Tianfang Ma, Yan Dong, Erik K. Flemington

School of Medicine Faculty Publications

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes ‘de novo’ transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, …

Nanobodies In The Fight Against Infectious Diseases: Repurposing Nature's Tiny Weapons, Dina Mohamed Moustafa, Soha S. Rizk, Shahira A. Elbanna, Hanzada Tawfik Nour El-Din, Ahmed Sherif Attia

Dentistry

Nanobodies are the smallest known antigen-binding molecules to date. Their small size, good tissue penetration, high stability and solubility, ease of expression, refolding ability, and negligible immunogenicity in the human body have granted them excellence over conventional antibodies. Those exceptional attributes of nanobodies make them promising candidates for various applications in biotechnology, medicine, protein engineering, structural biology, food, and agriculture. This review presents an overview of their structure, development methods, advantages, possible challenges, and applications with special emphasis on infectious diseases-related ones. A showcase of how nanobodies can be harnessed for applications including neutralization of viruses and combating antibiotic-resistant bacteria …

Mv140 Mucosal Vaccine Induces Targeted Immune Response For Enhanced Clearance Of Uropathogenic E Coli In Experimental Urinary Tract Infection, Paula Saz-Leal, Marianne Morris Ligon, Carmen María Diez-Rivero, Diego García-Ayuso, Soumitra Mohanty, Marcos Viñuela, Irene Real-Arévalo, Laura Conejero, Annelie Brauner, José Luis Subiza, Indira Uppugunduri Mysorekar

Faculty, Staff and Students Publications

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that …

Standard Rodent Diets Differentially Impact Alcohol Consumption, Preference, And Gut Microbiome Diversity, Aline Zaparte, Evan Dore, Selby White, Franciely Paliarin, Cameron Gabriel, Katherine Copenhaver, Samhita Basavanhalli, Emily Garcia, Rishith Vaddavalli, Meng Luo, Christopher M. Taylor, David Allen Welsh, Rajani Maiya

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 …

A Bioinformatic Analysis Of T-Cell Epitope Diversity In Sars-Cov-2 Variants: Association With Covid-19 Clinical Severity In The United States Population, Grace J. Kim, Jacob H. Elnaggar, Mallory Varnado, Amy K. Feehan, Darlene Tauzier, Rebecca Rose, Susanna L. Lamers, Maya Sevalia, Najah Nicholas, Elizabeth Gravois, Daniel Fort, Judy S. Crabtree, Lucio Miele

School of Graduate Studies Faculty Publications

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in …

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez

Faculty, Staff and Students Publications

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with …

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …