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Hyperbaric Oxygen Augments Susceptibility To C. Difficile Infection By Impairing Gut Microbiota Ability To Stimulate The Hif-1Α-Il-22 Axis In Ilc3, José L Fachi, Laís P Pral, Helder C Assis, Sarah Oliveira, Vinícius R Rodovalho, Jefferson A C Dos Santos, Mariane F Fernandes, Valquíria A Matheus, Renata Sesti-Costa, Paulo J Basso, Marina Flóro E Silva, Niels O S Câmara, Selma Giorgio, Marco Colonna, Marco A R Vinolo Jan 2024

Hyperbaric Oxygen Augments Susceptibility To C. Difficile Infection By Impairing Gut Microbiota Ability To Stimulate The Hif-1Α-Il-22 Axis In Ilc3, José L Fachi, Laís P Pral, Helder C Assis, Sarah Oliveira, Vinícius R Rodovalho, Jefferson A C Dos Santos, Mariane F Fernandes, Valquíria A Matheus, Renata Sesti-Costa, Paulo J Basso, Marina Flóro E Silva, Niels O S Câmara, Selma Giorgio, Marco Colonna, Marco A R Vinolo

2020-Current year OA Pubs

Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to


Leishmania Major Surface Components And Dkk1 Signalling Via Lrp6 Promote Migration And Longevity Of Neutrophils In The Infection Site, Olivia C Ihedioha, Haley Q Marcarian, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell Jan 2024

Leishmania Major Surface Components And Dkk1 Signalling Via Lrp6 Promote Migration And Longevity Of Neutrophils In The Infection Site, Olivia C Ihedioha, Haley Q Marcarian, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell

2020-Current year OA Pubs

BACKGROUND: Host-related factors highly regulate the increased circulation of neutrophils during

RESULTS: In this study, we further explored the potential role of DKK1-LRP6 signalling in the migration and longevity of activated neutrophils in the infection site using BALB/c mice with PMNs deficient in LRP6 (LRP6

CONCLUSION: Our results suggest that DKK1 signalling and


Unraveling The Role Of Hif And Epigenetic Regulation In Pulmonary Arterial Hypertension: Implications For Clinical Research And Its Therapeutic Approach, Ankita Mitra, Dan Yi, Zhiyu Dai, Vinicio De Jesus Perez Jan 2024

Unraveling The Role Of Hif And Epigenetic Regulation In Pulmonary Arterial Hypertension: Implications For Clinical Research And Its Therapeutic Approach, Ankita Mitra, Dan Yi, Zhiyu Dai, Vinicio De Jesus Perez

2020-Current year OA Pubs

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with high pulmonary pressure, which ultimately leads to right heart failure and premature death. Emerging evidence suggests that both hypoxia and epigenetics play a pivotal role in the pathogenesis of PAH development. In this review article, we summarize the current developments in regulation of hypoxia inducible factor (HIF) isoforms in PAH vascular remodeling and the development of suitable animal models for discovery and testing of HIF pathway-targeting PAH therapeutics. In addition, we also discuss the epigenetic regulation of HIF-dependent isoforms in PAH and its therapeutic potential from a new perspective …


A Global Survey Of Self-Reported Cancer Screening Practices By Health Professionals For Kidney Transplant Candidates And Recipients, Nida Saleem, Naoka Murakami, Et Al. Jan 2024

A Global Survey Of Self-Reported Cancer Screening Practices By Health Professionals For Kidney Transplant Candidates And Recipients, Nida Saleem, Naoka Murakami, Et Al.

2020-Current year OA Pubs

Cancer is a major cause of morbidity and mortality in kidney transplant recipients. Health professionals have a critical role in promoting cancer screening participation. From March 2023 to February 2024, an online survey was distributed to kidney transplant health professionals globally to assess their screening practices. We compared their reported screening practices to recommended guidelines and analyzed factors associated with these practices. We received 97 responses, and most were nephrologists (70%), and around 80% recommended breast, colorectal, and cervical cancer screening for kidney transplant candidates and recipients. About 85% recommended lung cancer screening for higher-risk individuals. Skin cancer screening recommendations …


Distinct Gene Expression Signatures Comparing Latent Tuberculosis Infection With Different Routes Of Bacillus Calmette-Guérin Vaccination, Richard F Silver, Mei Xia, Chad E Storer, Jessica R Jarvela, Michelle C Moyer, Azra Blazevic, David A Stoeckel, Erin K Rakey, Jan M Tennant, Johannes B Goll, Richard D Head, Daniel F Hoft Dec 2023

Distinct Gene Expression Signatures Comparing Latent Tuberculosis Infection With Different Routes Of Bacillus Calmette-Guérin Vaccination, Richard F Silver, Mei Xia, Chad E Storer, Jessica R Jarvela, Michelle C Moyer, Azra Blazevic, David A Stoeckel, Erin K Rakey, Jan M Tennant, Johannes B Goll, Richard D Head, Daniel F Hoft

2020-Current year OA Pubs

Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated …


Vodka2: A Fast And Accurate Method To Detect Non-Standard Viral Genomes From Large Rna-Seq Data Sets, Emna Achouri, Sébastien A Felt, Matthew Hackbart, Nicole S Rivera-Espinal, Carolina B López Dec 2023

Vodka2: A Fast And Accurate Method To Detect Non-Standard Viral Genomes From Large Rna-Seq Data Sets, Emna Achouri, Sébastien A Felt, Matthew Hackbart, Nicole S Rivera-Espinal, Carolina B López

2020-Current year OA Pubs

During viral replication, viruses carrying an RNA genome produce non-standard viral genomes (nsVGs), including copy-back viral genomes (cbVGs) and deletion viral genomes (delVGs), that play a crucial role in regulating viral replication and pathogenesis. Because of their critical roles in determining the outcome of RNA virus infections, the study of nsVGs has flourished in recent years, exposing a need for bioinformatic tools that can accurately identify them within next-generation sequencing data obtained from infected samples. Here, we present our data analysis pipeline, Viral Opensource DVG Key Algorithm 2 (VODKA2), that is optimized to run on a parallel computing environment for …


What Do Infectious Disease Specialists Think About Managing Long Covid?, Maureen D Lyons, Susan E Beekmann, Philip M Polgreen, Jonas Marschall Dec 2023

What Do Infectious Disease Specialists Think About Managing Long Covid?, Maureen D Lyons, Susan E Beekmann, Philip M Polgreen, Jonas Marschall

2020-Current year OA Pubs

This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.


Older Adults' And Caregivers' Perceptions About Urinary Tract Infection And Asymptomatic Bacteriuria Guidelines: A Qualitative Exploration, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Zoe Troubh, Mary C Politi Dec 2023

Older Adults' And Caregivers' Perceptions About Urinary Tract Infection And Asymptomatic Bacteriuria Guidelines: A Qualitative Exploration, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Zoe Troubh, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: To explore older adults' and caregivers' knowledge and perceptions of guidelines for appropriate antibiotics use for bacteria in the urine.

DESIGN: Semi-structured qualitative interviews.

SETTING: Infectious disease clinics, community senior living facilities, memory care clinics, and general public.

PARTICIPANTS: Patients 65 years or older diagnosed with a urinary tract infection (UTI) in the past two years, or caregivers of such patients.

METHODS: We conducted interviews between March and July 2023. We developed an interview guide based on the COM-B (capability, opportunity, motivation-behavior) behavior change framework. We thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques. …


Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry Dec 2023

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …


What Can The Plasma Proteome Tell Us About Platelets And (Vice Versa)?, Steven Bruzek, Marisol Betensky, Jorge Di Paola, Thomas Diacovo, Neil Goldenberg, Vera Ignjatovic Dec 2023

What Can The Plasma Proteome Tell Us About Platelets And (Vice Versa)?, Steven Bruzek, Marisol Betensky, Jorge Di Paola, Thomas Diacovo, Neil Goldenberg, Vera Ignjatovic

2020-Current year OA Pubs

Multi-omics approaches are being used increasingly to study physiological and pathophysiologic processes. Proteomics specifically focuses on the study of proteins as functional elements and key contributors to, and markers of the phenotype, as well as targets for diagnostic and therapeutic approaches. Depending on the condition, the plasma proteome can mirror the platelet proteome, and hence play an important role in elucidating both physiologic and pathologic processes. In fact, both plasma and platelet protein signatures have been shown to be important in the setting of thrombosis-prone disease states such as atherosclerosis and cancer. Plasma and platelet proteomes are increasingly being studied …


Correlating Deep Learning-Based Automated Reference Kidney Histomorphometry With Patient Demographics And Creatinine, Nicholas Lucarelli, Brandon Ginley, Jarcy Zee, Sayat Mimar, Anindya S. Paul, Sanjay Jain, Seung Seok Han, Luis Rodrigues, Tezcan Ozrazgat-Baslanti, Michelle L. Wong, Girish Nadkarni, William L. Clapp, Kuang-Yu Jen, Pinaki Sarder Dec 2023

Correlating Deep Learning-Based Automated Reference Kidney Histomorphometry With Patient Demographics And Creatinine, Nicholas Lucarelli, Brandon Ginley, Jarcy Zee, Sayat Mimar, Anindya S. Paul, Sanjay Jain, Seung Seok Han, Luis Rodrigues, Tezcan Ozrazgat-Baslanti, Michelle L. Wong, Girish Nadkarni, William L. Clapp, Kuang-Yu Jen, Pinaki Sarder

2020-Current year OA Pubs

KEY POINTS: The authors leverage the unique benefits of panoptic segmentation to perform the largest ever quantitation of reference kidney morphometry. Kidney features vary with age and sex; and glomeruli size may intricately link to creatinine, defying prior notions.

BACKGROUND: Reference histomorphometric data of healthy human kidneys are largely lacking because of laborious quantitation requirements. Correlating histomorphometric features with clinical parameters through machine learning approaches can provide valuable information about natural population variance. To this end, we leveraged deep learning (DL), computational image analysis, and feature analysis to associate the relationship of histomorphometry with patient age, sex, serum creatinine (SCr), …


Optimized Strategy For Real-Time Qpcr Detection Of Onchocerca Volvulus Dna In Pooled Simulium Sp. Blackfly Vectors, Mary Doherty, Peter U. Fischer, Et Al. Dec 2023

Optimized Strategy For Real-Time Qpcr Detection Of Onchocerca Volvulus Dna In Pooled Simulium Sp. Blackfly Vectors, Mary Doherty, Peter U. Fischer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, …


Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg Dec 2023

Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg

2020-Current year OA Pubs

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in …


Gut Microbiota Induces Weight Gain And Inflammation In The Gut And Adipose Tissue Independent Of Manipulations In Diet, Genetics, And Immune Development, Devesha H Kulkarni, Brigida Rusconi, Alexandria N Floyd, Elisabeth L Joyce, Khushi B Talati, Hrishi Kousik, Dereck Alleyne, Dalia L Harris, Lorena Garnica, Ryan Mcdonough, Shay S Bidani, Hrishikesh S Kulkarni, Elizabeth P Newberry, Keely G Mcdonald, Rodney D Newberry Dec 2023

Gut Microbiota Induces Weight Gain And Inflammation In The Gut And Adipose Tissue Independent Of Manipulations In Diet, Genetics, And Immune Development, Devesha H Kulkarni, Brigida Rusconi, Alexandria N Floyd, Elisabeth L Joyce, Khushi B Talati, Hrishi Kousik, Dereck Alleyne, Dalia L Harris, Lorena Garnica, Ryan Mcdonough, Shay S Bidani, Hrishikesh S Kulkarni, Elizabeth P Newberry, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Obesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, and gut microbes. Animal studies have identified roles for each of these, however the contribution(s) specifically attributed to the gut microbiota remain unclear, as studies have used combinations of genetically altered mice, high fat diet, and/or colonization of germ-free mice, which have an underdeveloped immune system. We investigated the role(s) of the gut microbiota driving obesity and inflammation independent of manipulations in diet and genetics in mice with fully developed immune systems. We demonstrate that the human obese gut microbiota alone was sufficient …


Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Kimberly S Quayle, Et Al. Nov 2023

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …


Heterogeneous Cardiac Sympathetic Innervation Gradients Promote Arrhythmogenesis In Murine Dilated Cardiomyopathy, Al-Hassan J Dajani, Carla Valenzuela-Ripoll, Ali Javaheri, Et Al. Nov 2023

Heterogeneous Cardiac Sympathetic Innervation Gradients Promote Arrhythmogenesis In Murine Dilated Cardiomyopathy, Al-Hassan J Dajani, Carla Valenzuela-Ripoll, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve …


Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team Nov 2023

Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team

2020-Current year OA Pubs

BACKGROUND: Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.

METHODS: We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).

RESULTS: From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% …


Mixed Methods Evaluation Of Handshake Antimicrobial Stewardship On Adult Inpatient Medicine Floors, Elizabeth A Neuner, Andrew Atkinson, Dan Ilges, Tamara Krekel, David J Ritchie, Alice F Bewley, Michael J Durkin, Kevin Hsueh, Sena Sayood Nov 2023

Mixed Methods Evaluation Of Handshake Antimicrobial Stewardship On Adult Inpatient Medicine Floors, Elizabeth A Neuner, Andrew Atkinson, Dan Ilges, Tamara Krekel, David J Ritchie, Alice F Bewley, Michael J Durkin, Kevin Hsueh, Sena Sayood

2020-Current year OA Pubs

OBJECTIVE: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital.

DESIGN: Retrospective observational study.

SETTING: 1,278-bed academic hospital.

PATIENTS: Adults admitted to non-ICU medicine services.

INTERVENTIONS: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data …


Perspectives On Research Needs In Healthcare Epidemiology, Infection Prevention, And Antimicrobial Stewardship: What's On The Horizon-Part Ii, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon Nov 2023

Perspectives On Research Needs In Healthcare Epidemiology, Infection Prevention, And Antimicrobial Stewardship: What's On The Horizon-Part Ii, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon

2020-Current year OA Pubs

In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) Transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and deimplementation, 6) healthcare outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors," 9) novel research methodologies, and 10) the …


Perspectives On Research Needs In Healthcare Epidemiology And Antimicrobial Stewardship: What's On The Horizon - Part I, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon Nov 2023

Perspectives On Research Needs In Healthcare Epidemiology And Antimicrobial Stewardship: What's On The Horizon - Part I, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon

2020-Current year OA Pubs

In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and de-implementation, 6) health care outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors", 9) novel research methodologies, and 10) …


Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al. Nov 2023

Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74


Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al. Nov 2023

Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness.

METHODS: We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants …


Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López Nov 2023

Copy-Back Viral Genomes Induce A Cellular Stress Response That Interferes With Viral Protein Expression Without Affecting Antiviral Immunity, Lavinia J González Aparicio, Yanling Yang, Matthew Hackbart, Carolina B. López

2020-Current year OA Pubs

Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in …


Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan Nov 2023

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

2020-Current year OA Pubs

BACKGROUND: Invasive infections caused by

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution.

RESULTS: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In …


Reducing Length Of Antibiotics For Children With Ear Infections: Protocol For A Cluster-Randomized Trial In The Usa, Amy Keith, Timothy C Jenkins, Sonja O'Leary, Amy B Stein, Sophie E Katz, Jason Newland, Deborah J Rinehart, Aiden Gilbert, Sherry Dodd, Cindy M Terrill, Holly M Frost Nov 2023

Reducing Length Of Antibiotics For Children With Ear Infections: Protocol For A Cluster-Randomized Trial In The Usa, Amy Keith, Timothy C Jenkins, Sonja O'Leary, Amy B Stein, Sophie E Katz, Jason Newland, Deborah J Rinehart, Aiden Gilbert, Sherry Dodd, Cindy M Terrill, Holly M Frost

2020-Current year OA Pubs

No abstract provided.


Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas Nov 2023

Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.

METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of …


Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson Nov 2023

Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson

2020-Current year OA Pubs

TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in …


Mycobacterium Tuberculosis Carrying The Rifampicin Drug-Resistance-Conferring Rpob Mutation H445y Is Associated With Suppressed Immunity Through Type I Interferons, Suhas Bobba, Nicole C Howard, Shibali Das, Mushtaq Ahmed, Linrui Tang, Shyamala Thirunavukkarasu, Michelle H Larsen, Barun Mathema, Maziar Divangahi, Shabaana A Khader Oct 2023

Mycobacterium Tuberculosis Carrying The Rifampicin Drug-Resistance-Conferring Rpob Mutation H445y Is Associated With Suppressed Immunity Through Type I Interferons, Suhas Bobba, Nicole C Howard, Shibali Das, Mushtaq Ahmed, Linrui Tang, Shyamala Thirunavukkarasu, Michelle H Larsen, Barun Mathema, Maziar Divangahi, Shabaana A Khader

2020-Current year OA Pubs

This study highlights the impact of specific rifampicin-resistance-conferring mutations on the host immune response to


Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang Oct 2023

Infants Exposed In Utero To Hurricane Maria Have Gut Microbiomes With Reduced Diversity And Altered Metabolic Capacity, Ai Zhang, David De Ángel Solá, Midnela Acevedo Flores, Lijuan Cao, Leran Wang, Josh G Kim, Phillip I Tarr, Barbara B Warner, Nicolás Rosario Matos, Leyao Wang

2020-Current year OA Pubs

The gut microbiome is a potentially important mechanism that links prenatal disaster exposures with increased disease risks. However, whether prenatal disaster exposures are associated with alterations in the infant's gut microbiome remains unknown. We established a birth cohort study named Hurricane as the Origin of Later Alterations in Microbiome (HOLA) after Hurricane Maria struck Puerto Rico in 2017. We enrolled vaginally born Latino term infants aged 2 to 6 months, including


Volatile Profiling Distinguishes Streptococcus Pyogenes From Other Respiratory Streptococcal Species, Amalia Z Berna, Joseph A Merriman, Leah Mellett, Danealle K Parchment, Michael G Caparon, Audrey R Odom John Oct 2023

Volatile Profiling Distinguishes Streptococcus Pyogenes From Other Respiratory Streptococcal Species, Amalia Z Berna, Joseph A Merriman, Leah Mellett, Danealle K Parchment, Michael G Caparon, Audrey R Odom John

2020-Current year OA Pubs

Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures