Digital Commons Network^™

Targeting Host Glycolysis As A Strategy For Antimalarial Development, Andrew J Jezewski, Yu-Hsi Lin, Julie A Reisz, Rachel Culp-Hill, Yasaman Barekatain, Victoria C Yan, Angelo D'Alessandro, Florian L Muller, Audrey R Odom John

Open Access Publications

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather …

The Crossroads Of Glycoscience, Infection, And Immunology, Tanya R Mckitrick, Margaret E Ackerman, Robert M Anthony, Clay S Bennett, Michael Demetriou, Gregory A Hudalla, Katharina Ribbeck, Stefan Ruhl, Christina M Woo, Loretta Yang, Seth J Zost, Ronald L Schnaar, Tamara L Doering

Open Access Publications

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell-cell interactions that initiate and regulate the host response and modulates the effects of antibodies and …

Phylum-Spanning Neuropeptide Gpcr Identification And Prioritization: Shaping Drug Target Discovery Pipelines For Nematode Parasite Control, Louise E Atkinson, Ciaran J Mccoy, Bethany A Crooks, Fiona M Mckay, Paul Mcveigh, Darrin Mckenzie, Allister Irvine, John Harrington, Bruce A Rosa, Makedonka Mitreva, Nikki J Marks, Aaron G Maule, Angela Mousley

Open Access Publications

Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite 'omics' offers an opportunity for the

Rotavirus Susceptibility Of Antibiotic-Treated Mice Ascribed To Diminished Expression Of Interleukin-22, Daniel Schnepf, Pedro Hernandez, Tanel Mahlakõiv, Stefania Crotta, Meagan E. Sullender, Stefan T. Peterson, Annette Ohnemus, Camille Michiels, Ian Gentle, Laure Dumoutier, Celso A. Reis, Andreas Diefenbach, Andreas Wack, Megan T. Baldridge, Peter Staeheli

Open Access Publications

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the …

Outcomes Associated With Social Distancing Policies In St Louis, Missouri, During The Early Phase Of The Covid-19 Pandemic, Elvin H. Geng, Joshua Schwab, Randi Foraker, Branson Fox, Christine M. Hoehner, Mario Schootman, Aaloke Mody, William Powderly, Byron Yount, Keith Woeltje, Maya Petersen

Open Access Publications

Importance: In the absence of a national strategy in response to the COVID-19 pandemic, many public health decisions fell to local elected officials and agencies. Outcomes of such policies depend on a complex combination of local epidemic conditions and demographic features as well as the intensity and timing of such policies and are therefore unclear.

Objective: To use a decision analytical model of the COVID-19 epidemic to investigate potential outcomes if actual policies enacted in March 2020 (during the first wave of the epidemic) in the St Louis region of Missouri had been delayed.

Design, Setting, and Participants: A previously …

A Canker Barking At The Wrong Knee: Thyronectria Austroamericana Septic Arthritis, Sasinuch Rutjanawech, Carlos Mejia-Chew, Chapelle Ayres, Andrej Spec

Open Access Publications

The mold

Diagnosis Of Mast Cell Activation Syndrome: A Global “Consensus-2”, Lawrence B. Afrin, Leonard B. Weinstock, Et Al

Open Access Publications

No abstract provided.

Contemporary Clinical Isolates Of Staphylococcus Aureus From Pediatric Osteomyelitis Patients Display Unique Characteristics In A Mouse Model Of Hematogenous Osteomyelitis, Philip M. Roper, Kara R. Eichelberger, Linda Cox, Luke O'Connor, Christine Shao, Caleb A. Ford, Stephanie A. Fritz, James E. Cassat, Deborah J. Veis

Open Access Publications

No abstract provided.

Molecular Characterization Of Microbiota In Cerebrospinal Fluid From Patients With Csf Shunt Infections Using Whole Genome Amplification Followed By Shotgun Sequencing, Paul Hodor, Christopher E Pope, Kathryn B Whitlock, Lucas R Hoffman, David L Limbrick, Patrick J Mcdonald, Jason S Hauptman, Jeffrey G Ojemann, Tamara D Simon

Open Access Publications

Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA …

Intent To Vaccinate Sars-Cov-2 Infected Children In Us Households: A Survey, Mehgan Teherani, Samridhi Banskota, Andres Camacho-Gonzalez, Alison G C Smith, Evan J Anderson, Carol M Kao, Charles Crepy D'Orleans, Andi L Shane, Austin Lu, Preeti Jaggi

Open Access Publications

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%,

An Essential, Kinetoplastid-Specific Gdp-Fuc: Β-D-Gal Α-1,2-Fucosyltransferase Is Located In The Mitochondrion Of Trypanosoma Brucei, Giulia Bandini, Sebastian Damerow, Maria Lucia Sempaio Guther, Hongjie Guo, Angela Mehlert, Jose Carlos Paredes Franco, Stephen Beverley, Michael A.J. Ferguson

Open Access Publications

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in

Efficacy And Breadth Of Adjuvanted Sars-Cov-2 Receptor-Binding Domain Nanoparticle Vaccine In Macaques, Hannah A. D. King, Rita E. Chen, James B. Case, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.

Postdischarge Prophylactic Antibiotics Following Mastectomy With And Without Breast Reconstruction, David K Warren, Kate M Peacock, Katelin B Nickel, Victoria J Fraser, Margaret A Olsen, Cdc Prevention Epicenter Program

Open Access Publications

BACKGROUND: Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI).

STUDY DESIGN: We studied a cohort of women aged 18-64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were …

Zika Virus Infection Of Pregnant Ifnar1-/- Mice Triggers Strain-Specific Differences In Fetal Outcomes, Ellie K. Bohm, Jennifer T. Vangorder-Braid, Anna S. Jaeger, Ryan V. Moriarty, John J. Baczenas, Natalie C. Bennett, Shelby L. O'Connor, Michael K. Fritsch, Nicole A. Fuhler, Kevin K. Noguchi, Matthew T. Aliota

Open Access Publications

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed congenital Zika syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015 to 2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian-/American-lineage ZIKV strains in an established

Spontaneous Bacterial Peritonitis Caused By Bordetella Hinzii, Grace C. Wang, Miranda J. Wallace, Gayathri Krishnan, Patrick D. Olson, Abigail L. Carlson, Gautam Dantas, James M. Fleckenstein

Open Access Publications

Although Bordetella hinzii coccobacilli is most commonly identified in respiratory tracts of birds and rodents, this organism has occasionally been isolated in human infections. We describe a case of B. hinzii spontaneous bacterial peritonitis in Missouri, USA. Whole-genome sequencing of blood and peritoneal fluid isolates confirmed B. hinzii infection.

Assessment Of Antibiotic De-Escalation By Spectrum Score In Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study, Dan Ilges, David J. Ritchie, Tamara Krekel, Elizabeth A. Neuner, Nicholas Hampton, Marin H. Kollef, Scott Micek

Open Access Publications

Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with …

Risk Factors And Medical Resource Utilization Of Respiratory Syncytial Virus, Human Metapneumovirus, And Influenza-Related Hospitalizations In Adults—A Global Study During The 2017–2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [Harti] Study), Ann R. Falsey, Edward E. Walsh, Yannick Vandenijck, Xiaohui Ren, Sofia Keim, Diye Kang, Pascale Peeters, James Witek, Gabriela Ispas

Open Access Publications

No abstract provided.

Value Of Packaged Testing For Sexually Transmitted Infections For Persons Who Inject Drugs Hospitalized With Serious Injection-Related Infections, Laura R. Marks, Hilary Reno, Stephen Y. Liang, Evan S. Schwarz, David B. Liss, Linda Jiang, Nathanial S. Nolan, Michael J. Durkin

Open Access Publications

Background: Persons who inject drugs (PWID) are frequently admitted for serious injection-related infections (SIRIs). PWID are also at risk for sexually transmitted infections (STIs).

Methods: We conducted a multicenter quality improvement project at 3 hospitals in Missouri. PWID with SIRI who received an infectious diseases consultation were prospectively identified and placed into an electronic database as part of a Centers for Disease Control and Prevention-funded quality improvement project. Baseline data were collected from 8/1/2019 to 1/30/2020. During the intervention period (2/1/2020-2/28/2021), infectious diseases physicians caring for patients received 2 interventions: (1) email reminders of best practice screening for HIV, viral …

A Randomized, Placebo-Controlled Trial Assessing The Effect Of Visbiome Es Probiotic In People With Hiv On Antiretroviral Therapy, Rachel M. Presti, Et Al

Open Access Publications

Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.

Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample

Results: Overall, 93 participants enrolled: 86% male, median …

Coronavirus Disease 2019-Associated Invasive Fungal Infection, John W. Baddley, George R. Thompson, Sharon C.-A. Chen, P. Lewis White, Melissa D. Johnson, M. Hong Nguyen, Ilan S. Schwartz, Andrej Spec, Luis Ostrosky-Zeichner, Brendan R. Jackson, Thomas F. Patterson, Peter G. Pappas

Open Access Publications

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. …

Toxoplasma Bradyzoites Exhibit Physiological Plasticity Of Calcium And Energy Stores Controlling Motility And Egress, Yong Fu, Kevin M. Brown, Nathaniel G. Jones, Silvia N.J. Moreno, L. David Sibley

Open Access Publications

No abstract provided.

Cell Death And Transcriptional Responses Induced In Larvae Of The Nematode Haemonchus Contortus By Toxins/Toxicants With Broad Phylogenetic Efficacy, Douglas P Jasmer, Bruce A Rosa, Makedonka Mitreva

Open Access Publications

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in

Toll-Like Receptor Signaling In The Establishment And Function Of The Immune System, Jahnavi Aluri, Megan A Cooper, Laura G Schuettpelz

Open Access Publications

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in …

Impact Of Antibiotic Heterogeneity By Periodic Antibiotic Monitoring And Supervision Strategy At Two Units With Different Prevalences Of Multidrug-Resistant Organisms, Surachai Chaononghin, Kittiya Jantarathaneewat, David J Weber, David K Warren, Anucha Apisarnthanarak

Open Access Publications

In an intensive care unit, antibiotic heterogeneity led to an increase in antibiotic heterogeneity index (P = .002) and a reduction in carbapenem-resistance Enterobacteriaceae incidence (P = .04). In a general medicine unit with low prevalence of multidrug-resistant organisms, antibiotic heterogeneity index and incidence of multidrug-resistant organisms did not improve.

Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer

Open Access Publications

Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …

Bictegravir-Based Antiretroviral Therapy-Associated Accelerated Hyperglycemia And Diabetes Mellitus, Nathanial S. Nolan, Samantha Adamson, Dominic Reeds, Jane A. O'Halloran

Open Access Publications

Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is first line for treatment of people with human immunodeficiency virus (PWH). Emerging data suggest the possibility of adverse metabolic effects of these medications. We describe 3 cases in which PWH developed hyperglycemia and ketoacidosis within months of being switched to bictegravir-based ART.

Public Preferences For Social Distancing Policy Measures To Mitigate The Spread Of Covid-19 In Missouri, Ingrid Eshun-Wilson, Aaloke Mody, Virginia Mckay, Matifadza Hlatshwayo, Cory Bradley, Vetta Thompson, David V. Glidden, Elvin H. Geng

Open Access Publications

Importance: Policies to promote social distancing can minimize COVID-19 transmission but come with substantial social and economic costs. Quantifying relative preferences among the public for such practices can inform locally relevant policy prioritization and optimize uptake.

Objective: To evaluate relative utilities (ie, preferences) for COVID-19 pandemic social distancing strategies against the hypothetical risk of acquiring COVID-19 and anticipated income loss.

Design, Setting, and Participants: This survey study recruited individuals living in the Missouri area from May to June 2020 via randomly distributed unincentivized social media advertisements and local recruitment platforms for members of minority racial and ethnic groups. Participants answered …

Strategies For Disseminating And Implementing Covid-19 Vaccines In Rural Areas, Beth Prusaczyk

Open Access Publications

The United States has well-documented rural-urban health disparities, and it is imperative that these are not exacerbated by an inefficient rollout of coronavirus disease 2019 (COVID-19) vaccines to rural areas. In addition to the preexisting barriers to delivering and receiving health care in rural areas, such as high patient:provider ratios and long geographic distances between patients and providers, rural residents are significantly more likely to say they have no intention of receiving a COVID-19 vaccine, compared with urban residents. To overcome these barriers and ensure that rural residents receive the vaccine, officials and communities should look to previous research on …

The Top 100 Cited Papers In The Field Of Iron Deficiency In Humans: A Bibliometric Study, John L. Frater

Open Access Publications

No abstract provided.

Effect Of Clinical Isolate Or Cleavage Site Mutations In The Sars-Cov-2 Spike Protein On Protein Stability, Cleavage, And Cell–Cell Fusion, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch

Open Access Publications

No abstract provided.