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Evaluation Of Oxacillin And Cefoxitin Disk Diffusion And Microbroth Dilution Methods For Detecting Meca-Mediated Β-Lactam Resistance In Contemporary Staphylococcus Epidermidis Isolates, Samia N Naccache, Katrina Callan, Carey-Ann D. Burnham, Meghan A Wallace, Lars F Westblade, Jennifer Dien Bard, Staphylococcus Ad Hoc Working Group Of The Clsi Antimicrobial Susceptibility Testing Subcommittee

Open Access Publications

Methicillin (β-lactam) resistance in

Telemedicine Infectious Diseases Consultations And Clinical Outcomes: A Systematic Review, Jason P. Burnham, Stephanie A. Fritz, Lauren H. Yaeger, Graham A. Colditz

Open Access Publications

Background: Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically reviewed. We reviewed the current evidence for clinical effectiveness of telemedicine infectious diseases consultations, including outcomes of mortality, hospital readmission, antimicrobial use, cost, length of stay, adherence, and patient satisfaction.

Methods: We queried Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov 1997- through August 5, 2019, for studies looking at clinical outcomes of infectious diseases in the setting of telemedicine use. We did not restrict …

Entry By Multiple Picornaviruses Is Dependent On A Pathway That Includes Tnk2, Wasl, And Nck1, Hongbing Jiang, Christian Leung, Stephen Tahan, David Wang

Open Access Publications

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes,

Gut Microbiota: From The Forgotten Organ To A Potential Key Player In The Pathology Of Alzheimer's Disease, Dong-Oh Seo, David M Holtzman

Open Access Publications

More than 300 years ago, Antony van Leewenhoeck first described observing single-celled microorganisms, which he termed "animalcules," examining his saliva under a microscope. Although the idea of the coexistence of microorganisms in our body is not new, we have only recently been able to investigate their ecological relationship to our body, with the development of high-throughput molecular techniques. The diverse microorganism communities residing in our guts are established and maintained by complex interactions among microorganisms and their host. Notably, their alteration has been implicated in influencing various diseases including neurological diseases. Alzheimer's disease (AD) is the most common cause of …

Human Monoclonal Antibodies Against Chikungunya Virus Target Multiple Distinct Epitopes In The E1 And E2 Glycoproteins, Jose A. Quiroz, Ryan J. Malonis, Larissa B. Thackray, Courtney A. Cohen, Jesper Pallesen, Rohit K. Jangra, Rebecca S. Brown, Daniel Hofmann, Frederick W. Holtsberg, Sergey Shulenin, Elisabeth K. Nyakatura, Lorellin A. Durnell, Vinayak Rayannavar, Johanna P. Daily, Andrew B. Ward, M. Javad Aman, John M. Dye, Kartik Chandran, Michael S. Diamond, Margaret Kielian, Jonathan R. Lai

Open Access Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two …

Bjc Today

BJC Today

No abstract provided.

Staphylococcus Aureus Infects Osteoclasts And Replicates Intracellularly, Jennifer L Krauss, Philip M Roper, Anna Ballard, Chien-Cheng Shih, James A J Fitzpatrick, James E Cassat, Pei Ying Ng, Nathan J Pavlos, Deborah J Veis

Open Access Publications

Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused by

Htlv-1 Viral Oncogene Hbz Drives Bone Destruction In Adult T Cell Leukemia, Jingyu Xiang, Daniel A Rauch, Devra D Huey, Amanda R Panfil, Xiaogang Cheng, Alison K Esser, Xinming Su, John C Harding, Yalin Xu, Gregory C Fox, Francesca Fontana, Takayuki Kobayashi, Junyi Su, Hemalatha Sundaramoorthi, Wing Hing Wong, Yizhen Jia, Thomas J Rosol, Deborah J Veis, Patrick L Green, Stefan Niewiesk, Lee Ratner, Katherine N Weilbaecher

Open Access Publications

Osteolytic bone lesions and hypercalcemia are common, serious complications in adult T cell leukemia/lymphoma (ATL), an aggressive T cell malignancy associated with human T cell leukemia virus type 1 (HTLV-1) infection. The HTLV-1 viral oncogene HBZ has been implicated in ATL tumorigenesis and bone loss. In this study, we evaluated the role of HBZ on ATL-associated bone destruction using HTLV-1 infection and disease progression mouse models. Humanized mice infected with HTLV-1 developed lymphoproliferative disease and continuous, progressive osteolytic bone lesions. HTLV-1 lacking HBZ displayed only modest delays to lymphoproliferative disease but significantly decreased disease-associated bone loss compared with HTLV-1-infected mice. …

Incidence And Diagnostic Yield Of Repeat Urine Culture In Hospitalized Patients: An Opportunity For Diagnostic Stewardship, Kap Sum Foong, Satish Munigala, Ronald Jackups, Melanie L Yarbrough, Carey-Ann D. Burnham, David K Warren

Open Access Publications

There is limited knowledge on the incidence, diagnostic yield, and cost associated with inappropriate repeat urine cultures. The factors that affect repeat urine culturing practices are not well understood. We conducted a retrospective study of adult inpatients who had ≥1 urine culture performed during their hospitalization between January 2015 and February 2018. We analyzed the proportion of inappropriate repeat urine cultures performed <48 h after the index culture. We defined an inappropriate repeat urine culture to be a repeat urine culture performed following a negative index culture or a repeat urine specimen obtained from the same urinary catheter. Overall, 28,141 urine cultures were performed on 21,306 patients. There were 2,060 (7.3%) urine cultures repeated in <48 h. Of these, 1,120 (54.4%) urine cultures were inappropriate. Predictors for inappropriate repeat urine cultures included collection of the initial urine sample for culture in the emergency department (adjusted odds ratio [aOR], 5.65; 95% confidence interval [CI], 4.70 to 6.78), male gender (aOR, 1.61; 95% CI, 1.42 to 1.84), congestive heart failure (aOR, 1.20; 95% CI, 1.03 to 1.38), and a longer hospital stay (aOR, 1.01 per day; 95% CI, 1.00 to 1.01). A patient with an index urine culture obtained from an indwelling catheter (aOR, 0.65; 95% CI, 0.53 to 0.80) was less likely to have an inappropriate repeat culture. Among 1,120 negative index urine cultures, only 4.7% of repeat cultures were positive for bacteriuria. The estimated laboratory charges for inappropriate repeat urine cultures were $16,800 over the study period. Among inpatients, over half of all urine cultures repeated in <48 h were inappropriate. This offers an opportunity for diagnostic stewardship and optimization of antimicrobial use.

Multispectral Tracing In Densely Labeled Mouse Brain With Ntracer, Douglas H Roossien, John M Webb, Cristina Mazuski, Erik D Herzog, Et Al.

2010-2019 OA Pubs

SUMMARY: This note describes nTracer, an ImageJ plug-in for user-guided, semi-automated tracing of multispectral fluorescent tissue samples. This approach allows for rapid and accurate reconstruction of whole cell morphology of large neuronal populations in densely labeled brains.

AVAILABILITY AND IMPLEMENTATION: nTracer was written as a plug-in for the open source image processing software ImageJ. The software, instructional documentation, tutorial videos, sample image and sample tracing results are available at https://www.cai-lab.org/ntracer-tutorial.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification Of 4-Amino-Thieno[2,3-D]Pyrimidines As Qcrb Inhibitors In Mycobacterium Tuberculosis, Gregory A Harrison, Anne E Mayer Bridwell, Megh Singh, Keshav Jayaraman, Leslie A Weiss, Rachel L Kinsella, Janessa S Aneke, Kelly Flentie, Miranda E Schene, Margaret Gaggioli, Samantha D Solomon, Scott A Wildman, Marvin J Meyers, Christina L Stallings

Open Access Publications

Antibiotic resistance is a global crisis that threatens our ability to treat bacterial infections, such as tuberculosis, caused by

Comparative Genomics Of Antibiotic-Resistant Uropathogens Implicates Three Routes For Recurrence Of Urinary Tract Infections, Robert Thänert, Kimberly A Reske, Tiffany Hink, Meghan A Wallace, Bin Wang, Drew J Schwartz, Sondra Seiler, Candice Cass, Carey-Ann D. Burnham, Erik R Dubberke, Jennie H Kwon, Gautam Dantas

Open Access Publications

The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic

Mucosal Infection Rewires Tnfɑ Signaling Dynamics To Skew Susceptibility To Recurrence, Lu Yu, Valerie P. O'Brien, Jonathan Livny, Denise Dorsey, Nirmalya Bandyopadhyay, Marco Colonna, Michael G. Caparon, Elisha D.O. Roberson, Scott J. Hultgren, Thomas Hannan

Open Access Publications

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice …

Noroviruses Subvert The Core Stress Granule Component G3bp1 To Promote Viral Vpg-Dependent Translation, Myra Hosmillo, Jia Lu, Michael R. Mcallaster, James B. Eaglesham, Xinjie Wang, Edward Emmott, Patricia Domingues, Yasmin Chaudhry, Tim J. Fitzmaurice, Matthew K.H. Tung, Marc Dominik Panas, Gerald Mcinerney, Nicolas Locker, Craig B. Wilen, Ian G. Goodfellow

Open Access Publications

Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the

How Genomics Can Be Used To Understand Host Susceptibility To Enteric Infection, Aiding In The Development Of Vaccines And Immunotherapeutic Interventions, Lynda Mottram, Subhra Chakraborty, Eric Cox, James Fleckenstein

Open Access Publications

Thanks to the modern sequencing era, the extent to which infectious disease imposes selective pressures on the worldwide human population is being revealed. This is aiding our understanding of the underlying immunological and host mechanistic defenses against these pathogens, as well as potentially assisting in the development of vaccines and therapeutics to control them. As a consequence, the workshop "How genomics can be used to understand host susceptibility to enteric infection, aiding in the development of vaccines and immunotherapeutic interventions" at the VASE 2018 meeting, aimed to discuss how genomics and related tools could be used to assist Shigella and …

Host And Viral Mechanisms Of Congenital Zika Syndrome, Brooke Liang, José Paulo Guida, Maria Laura Costa Do Nascimento, Indira U Mysorekar

Open Access Publications

In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by

Novel Cell Adhesion/Migration Pathways Are Predictive Markers Of Hdac Inhibitor Resistance In Cutaneous T Cell Lymphoma, Jared M Andrews, Jennifer A Schmidt, Kenneth R Carson, Amy C Musiek, Neha Mehta-Shah, Jacqueline E Payton

Open Access Publications

BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy.

METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks …

Bjc Today

BJC Today

No abstract provided.

Low Frequency Of Regulatory B-Cells And Increased Cd4+ And Cd8+ Interferon-Γ-Producing Cells In Patients With Tropical Spastic Paraparesis Associated With Human T-Cell Lymphotropic Virus Type, Yulieth Cristina Bermúdez Burbano, Angie Vanessa Caicedo Paz, Cristhian Camilo Rivera Caldon, Juan Sebastián Rodríguez Constain, Gloria Inés Ávila Gonzáles, Julio César Klínger Hernández, Nancy Marin-Agudelo, Rosa Amalia Dueñas-Cuellar, Victoria Eugenia Niño Castaño

Open Access Publications

INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown.

METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects.

RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in …

Low Frequency Of Regulatory B-Cells And Increased Cd4+ And Cd8+ Interferon-Γ-Producing Cells In Patients With Tropical Spastic Paraparesis Associated With Human T-Cell Lymphotropic Virus Type, Yulieth Cristina Bermúdez Burbano, Angie Vanessa Caicedo Paz, Cristhian Camilo Rivera Caldon, Juan Sebastián Rodríguez Constain, Gloria Inés Ávila Gonzáles, Julio César Klínger Hernández, Nancy Marin-Agudelo, Rosa Amalia Dueñas-Cuellar, Victoria Eugenia Niño Castaño

Open Access Publications

INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown.

METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects.

RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in …

Telemedicine Infectious Diseases Consultations And Clinical Outcomes: A Systematic Review And Meta-Analysis Protocol, Jason P Burnham, Stephanie A Fritz, Lauren H Yaeger, Graham A Colditz

Open Access Publications

BACKGROUND: Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically studied and reviewed. The proposed systematic review will evaluate the current evidence regarding the effect of telemedicine infectious diseases consultation on a range of clinical outcomes, including mortality, hospital readmission, antimicrobial use, and cost.

METHOD/DESIGN: Standard systematic review methodology will be used, with searches of Ovid MEDLINE 1946-, https://embase.com/ 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and https://clinicaltrials.gov/ 1997-. There will be no restriction on language or year of publication. …

Eosinophils Downregulate Lung Alloimmunity By Decreasing Tcr Signal Transduction, Oscar Okwudiri Onyema, Yizhan Guo, Bayan Mahgoub, Qing Wang, Amir Manafi, Zhongcheng Mei, Anirban Banerjee, Dongge Li, Mark H. Stoler, Melissa T. Zaidi, Adam G. Schrum, Daniel Kreisel, Andrew E. Gelman, Elizabeth A. Jacobsen, Alexander Sasha Krupnick

Open Access Publications

Despite the accepted notion that granulocytes play a universally destructive role in organ and tissue grafts, it has been recently described that eosinophils can facilitate immunosuppression-mediated acceptance of murine lung allografts. The mechanism of eosinophil-mediated tolerance, or their role in regulating alloimmune responses in the absence of immunosuppression, remains unknown. Using lung transplants in a fully MHC-mismatched BALB/c (H2d) to C57BL/6 (H2b) strain combination, we demonstrate that eosinophils downregulate T cell-mediated immune responses and play a tolerogenic role even in the absence of immunosuppression. We further show that such downregulation depends on PD-L1/PD-1-mediated synapse formation between eosinophils and T cells. …

The Current State Of Animal Models And Genomic Approaches Towards Identifying And Validating Molecular Determinants Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease, Allison N Bucsan, Smriti Mehra, Shabaana A Khader, Deepak Kaushal

2010-2019 OA Pubs

Animal models are important in understanding both the pathogenesis of and immunity to tuberculosis (TB). Unfortunately, we are beginning to understand that no animal model perfectly recapitulates the human TB syndrome, which encompasses numerous different stages. Furthermore, Mycobacterium tuberculosis infection is a very heterogeneous event at both the levels of pathogenesis and immunity. This review seeks to establish the current understanding of TB pathogenesis and immunity, as validated in the animal models of TB in active use today. We especially focus on the use of modern genomic approaches in these models to determine the mechanism and the role of specific …

Bjc Today

BJC Today

No abstract provided.

Reaching The End Of The Line: Urinary Tract Infections, Kevin O Tamadonfar, Natalie S Omattage, Caitlin N Spaulding, Scott J Hultgren

Open Access Publications

Urinary tract infections (UTIs) cause a substantial health care burden. UTIs (i) are most often caused by uropathogenic

Covert Pathogenesis: Transient Exposures To Microbes As Triggers Of Disease, Nicole M. Gilbert, Amanda L. Lewis

Open Access Publications

No abstract provided.

Association Of Blood Concentrations Of Complement Split Product Ic3b And Serum C3 With Systemic Lupus Erythematosus Disease Activity, Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson

Open Access Publications

OBJECTIVE: To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE).

METHODS: A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b …

Developing And Assessing The Feasibility Of A Home-Based Preexposure Prophylaxis Monitoring And Support Program, Aaron J Siegler, Kenneth H Mayer, Albert Y Liu, Rupa R Patel, Lauren M Ahlschlager, Colleen S Kraft, Rossi Fish, Sarah E Wiatrek, Patrick S Sullivan

2010-2019 OA Pubs

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available.

A Randomized, Placebo-Controlled Trial Of Fidaxomicin For Prophylaxis Of Clostridium Difficile-Associated Diarrhea In Adults Undergoing Hematopoietic Stem Cell Transplantation, Kathleen M. Mullane, Erik R. Dubberke, Et Al

Open Access Publications

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.

Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. …

Phosphatidylcholine Synthesis Through Cholinephosphate Cytidylyltransferase Is Dispensable In Leishmania Major, Samrat Moitra, Mattie C. Pawlowic, Fong-Fu Hsu, Kai Zhang

Open Access Publications

No abstract provided.