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Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Vaccination And The Defence Of Democracy – Authors’ Reply, Richard M Carpiano, Timothy Callahan, Jad A Elharake, Peter Hotez

Faculty, Staff and Students Publications

No abstract provided.

Design, Synthesis, X-Ray Crystallography, And Biological Activities Of Covalent, Non-Peptidic Inhibitors Of Sars-Cov-2 Main Protease, Md Ashraf-Uz-Zaman, Teck Khiang Chua, Xin Li, Yuan Yao, Bala Krishna Moku, Chandra Bhushan Mishra, Vasanthi Avadhanula, Pedro A Piedra, Yongcheng Song

Faculty, Staff and Students Publications

Highly contagious SARS-CoV-2 coronavirus has infected billions of people worldwide with flu-like symptoms since its emergence in 2019. It has caused deaths of several million people. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and therefore a drug target. Several series of covalent inhibitors of Mpro were designed and synthesized. Structure-activity relationship studies show that 1) several chloroacetamide- and epoxide-based compounds targeting Cys145 are potent inhibitors with IC50 values as low as 0.49 μM, and 2) Cys44 of Mpro is not nucleophilic for covalent inhibitor design. High resolution X-ray studies revealed the protein-inhibitor interactions and mechanisms of inhibition. …

Neurovascular Complications Of Iatrogenic Fusarium Solani Meningitis, Nora Strong, Grant Meeks, Sunil A Sheth, Louise Mccullough, Julian A Villalba, Chunfeng Tan, Andrew Barreto, Audrey Wanger, Michelle Mcdonald, Peter Kan, Hashem Shaltoni, Jose Campo Maldonado, Victoria Parada, Ameer E Hassan, Sarah Reagan-Steiner, Tom Chiller, Jeremy A W Gold, Dallas J Smith, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

New Sepsis Diagnostics And Their Impacts On Clinical Decision-Making And Treatment Protocols, Allison B Chambliss, Sridevi Devaraj, Jeremiah S Hinson, Sophie E Katz, Russell B Kerbel, Nathan A Ledeboer

Faculty, Staff and Students Publications

No abstract provided.

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Nivolumab Monotherapy Or Combination With Ipilimumab With Or Without Cobimetinib In Previously Treated Patients With Pancreatic Adenocarcinoma (Checkmate 032), Margaret Callahan, Asim Amin, Frederic J Kaye, Michael A Morse, Matthew H Taylor, Katriina J Peltola, Padmanee Sharma, Eileen M O'Reilly, Stephanie Meadows Shropshire, Shaun O'Brien, Marina Tschaika, Dung T Le

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer.

METHODS: In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Chronic Wasting Disease: State Of The Science, Jason C Bartz, Rebeca Benavente, Byron Caughey, Sonja Christensen, Allen Herbst, Edward A Hoover, Candace K Mathiason, Debbie Mckenzie, Rodrigo Morales, Marc D Schwabenlander, Daniel P Walsh, The Nc North American Interdisciplinary Chronic Wasting Disease Research Consortium Members

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together. The NC1209 (North American interdisciplinary chronic wasting disease research consortium) is composed of scientists from different disciplines involved with investigating and managing CWD. Leveraging this broad breadth of expertise, the Consortium has created a state-of-the-science …

Immune Evasion, Infectivity, And Fusogenicity Of Sars-Cov-2 Ba286 And Flip Variants, Panke Qu, Kai Xu, Julia N Faraone, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had …

Identification Of A Novel Cg307 Sub-Clade In Third-Generation-Cephalosporin-Resistant, Selvalakshmi Selvaraj Anand, Chin-Ting Wu, Jordan Bremer, Micah Bhatti, Todd J Treangen, Awdhesh Kalia, Samuel A Shelburne, William C Shropshire

Faculty, Staff and Student Publications

Despite the notable clinical impact, recent molecular epidemiology regarding third-generation-cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in the USA remains limited. We performed whole-genome sequencing of 3GC-R K. pneumoniae bacteraemia isolates collected from March 2016 to May 2022 at a tertiary care cancer centre in Houston, TX, USA, using Illumina and Oxford Nanopore Technologies platforms. A comprehensive comparative genomic analysis was performed to dissect population structure, transmission dynamics and pan-genomic signatures of our 3GC-R K. pneumoniae population. Of the 178 3GC-R K. pneumoniae bacteraemias that occurred during our study time frame, we were able to analyse 153 (86 %) bacteraemia isolates, 126 …

Transcription-Replication Interactions Reveal Bacterial Genome Regulation, Andrew W Pountain, Peien Jiang, Tianyou Yao, Ehsan Homaee, Yichao Guan, Kevin J C Mcdonald, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Ido Golding, Itai Yanai

Faculty, Staff and Student Publications

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of …

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations And Emergency Department Visits In Infants, Leila C Sahni, Samantha M Olson, Natasha B Halasa, Laura S Stewart, Marian G Michaels, John V Williams, Janet A Englund, Eileen J Klein, Mary A Staat, Elizabeth P Schlaudecker, Rangaraj Selvarangan, Jennifer E Schuster, Geoffrey A Weinberg, Peter G Szilagyi, Julie A Boom, Manish M Patel, Flor M Muñoz, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

IMPORTANCE: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited.

OBJECTIVE: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Antiretroviral Therapy In Pregnancy: A 2023 Review Of The Literature, Alison N Goulding, Kasey Meeks, Lena Shay, Sarah Casey, Colton Applegarth, Jennifer Mckinney

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA.

RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple …

Collaboration And Growth In A Large Research Cooperative: A Network Analytic Approach, Lori J Ducharme, Kayo Fujimoto, Jacky Kuo, Jonathan Stewart, Bruce Taylor, John Schneider

Faculty, Staff and Student Publications

Research networks encourage team science and facilitate collaboration within and across research teams. While many analyses have examined the output of these collaborative networks (e.g., authorship networks, publications, grant applications), less attention has been paid to the formative phases of these initiatives. This article presents analyses of a whole-network survey of investigators participating in a new research initiative, and examines the development of collaborative ties over the network's first year. In particular, we examine the influence of research center affiliation, seniority, and prior network experience on the number and structure of collaborative ties, including participants' bridging and broker roles. Such …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Methods: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the …

Burden Of Dog Bite Injuries And Wound Management Practices To Prevent Rabies Among Dog Owners, Dhawani Julka, Amir M Khan, Nitu Kumari, Ujjwal Soni

Faculty, Staff and Student Publications

BACKGROUND: Despite members of dog-owning families being at a higher risk of dog bites owing to their proximity to dogs in their household, there are hardly any studies from India which focus on the burden of dog bites among them and their rabies control and prevention practices. This study aimed to estimate the burden of dog bites among dog owners and their wound management practices to prevent rabies.

MATERIALS AND METHODS: A cross-sectional study was conducted among pet dog owners in a high-end housing society of National Capital Region of Delhi. A pre-tested and pre-validated schedule was used to collect …

Bloodstream Infections After Solid Organ Transplantation: Clinical Epidemiology And Antimicrobial Resistance (2016–21), Max W Adelman, Ashton A Connor, Enshuo Hsu, Ashish Saharia, Constance M Mobley, David W Victor, Mark J Hobeika, Jiejian Lin, Kevin A Grimes, Elizabeth Ramos, Claudia Pedroza, Elizabeth W Brombosz, R Mark Ghobrial, Cesar A Arias

Faculty, Staff and Student Publications

Background: Solid organ transplant (SOT) recipients are at risk of bloodstream infections (BSIs) with MDR organisms (MDROs).

Objectives: To describe the epidemiology of BSI in the year after several types of SOT, as well as the prevalence of MDRO infections in this population.

Methods: We conducted a single-centre, retrospective study of kidney, liver, heart, and multi-organ transplantation patients. We examined BSIs ≤1 year from SOT and classified MDRO phenotypes for Staphylococcus aureus, enterococci, Enterobacterales, Pseudomonas aeruginosa and Candida spp. We compared BSI characteristics between SOT types and determined risk factors for 90 day mortality.

Results: We included 2293 patients …

Knowledge And Attitudes On Contraception And Reproductive Health In Women With Hiv, Anna Henricks, Samantha Singal, Dana Hughes, Sean Kelly, Jessica L Castilho, Jamison Norwood

Faculty, Staff and Student Publications

BACKGROUND: For reasons not fully explained to date, contraception usage among women with HIV remains low. The aim of our study was to understand attitudes toward and lifetime use of contraception among women with HIV.

METHODS: We administered an anonymous, community-informed, voluntary survey to cisgender, English-speaking women with HIV (≥18 years of age) at a Southern urban HIV clinic. It included multiple choice and Likert-scale questions on reproductive health. Participants reported contraception use, recollection of provider conversations about contraception, and perceived empowerment and knowledge regarding reproductive health. We used chi-square and Fisher exact tests to compare attitudes and prior conversations …

Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron

Faculty, Staff and Student Publications

Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic …

Locoregional Therapies In Immunologically "Cold" Tumors: Opportunities And Clinical Trial Design Considerations, Pavlos Msaouel, Rahul A Sheth

Faculty, Staff and Student Publications

Immunotherapy has revolutionized cancer management, but many tumors, particularly immunologically "cold" tumors, remain resistant to the therapy. The combination of conventional systemic immunotherapies and locoregional interventional radiology approaches is being explored to transform these cold tumors into immunologically active "hot" ones. The present article uses the example of chromophobe renal cell carcinoma (ChRCC), a renal cell carcinoma subtype resistant to current systemic immunotherapies, to address practical and conceptual challenges that have prevented the activation of clinical trials specifically designed for this malignancy to date. The practical framework discussed herein can help overcome logistic and funding limitations and facilitate the development …

A Zika Virus Protein Expression Screen In Drosophila To Investigate Targeted Host Pathways During Development, Nichole Link, J Michael Harnish, Brooke Hull, Shelley Gibson, Miranda Dietze, Uchechukwu E Mgbike, Silvia Medina-Balcazar, Priya S Shah, Shinya Yamamoto

Faculty, Staff and Students Publications

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused …

Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Mark P Hamilton, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Zika virus congenital infection evades double-stranded RNA detection and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. Understanding how viruses can persist and replicate in the placenta without causing overt cellular or tissue damage is fundamental to deciphering mechanisms of maternal-fetal vertical transmission.

OBJECTIVE: Placenta-specific microRNAs are believed to be a tenet of viral resistance at the maternal-fetal interface. We aimed to test the hypothesis that the Zika virus functionally disrupts placental microRNAs, enabling viral persistence and fetal pathogenesis.

STUDY DESIGN: To test this hypothesis, we used orthogonal approaches in human and …