38 results on '"Altman DR"'
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2. Polymicrobial methicillin-resistant Staphylococcus aureus bloodstream infections.
- Author
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Escalona A, Hayashi E, Evans M, van Bakel H, Alburquerque B, Dupper AC, McBride R, and Altman DR
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Case-Control Studies, Aged, Risk Factors, New York City epidemiology, Adult, Intensive Care Units statistics & numerical data, Enterococcus drug effects, Enterococcus isolation & purification, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Aged, 80 and over, Methicillin-Resistant Staphylococcus aureus isolation & purification, Methicillin-Resistant Staphylococcus aureus drug effects, Staphylococcal Infections microbiology, Staphylococcal Infections epidemiology, Bacteremia microbiology, Bacteremia epidemiology, Bacteremia mortality, Coinfection microbiology, Coinfection epidemiology
- Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a serious public health concern. At times, MRSA is isolated from the blood along with other pathogens, the significance and consequences of which are not well described. This study aims to outline the clinical characteristics and outcomes of those with polymicrobial MRSA BSI compared with those with monomicrobial MRSA BSI. We conducted a retrospective case-control study of those with and without polymicrobial MRSA BSI from 2014 to 2022 at a single quaternary care center in New York City. Risk factors and outcomes for polymicrobial MRSA BSI were assessed using logistic regression analyses. Of 559 patients with MRSA BSI during the study period, 49 (9%) had polymicrobial MRSA BSI. Gram-positive Enterococcus (23%) was the most common co-pathogen. The presence of urinary ( P = 0.02) and gastrointestinal ( P < 0.01) devices was significantly associated with polymicrobial MRSA BSI. Polymicrobial MRSA BSI was associated with intensive care unit (ICU) admission after BSI ( P = 0.01). Mortality did not differ. While polymicrobial MRSA BSI is relatively uncommon, it complicates an already complex clinical scenario of MRSA BSI.IMPORTANCE Staphylococcus aureus is a common human pathogen associated with severe disease and high mortality rates. Although clinically observed, little is known about the impact of polymicrobial staphylococcal bloodstream infection. This study evaluates polymicrobial methicillin-resistant S. aureus bloodstream infection (BSI), highlighting the increased risk of intensive care unit admission and impact on morbidity. Identifying risk factors for polymicrobial BSI, such as the presence of specific devices, can aid in early recognition and targeted interventions. Clarifying the risks and outcomes of polymicrobial infections can lead to strategies to minimize and manage these infections and explore the potential interactions between pathogens., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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3. Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study.
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Cohn H, Bloom N, Cai GY, Clark JJ, Tarke A, Bermúdez-González MC, Altman DR, Lugo LA, Lobo FP, Marquez S, Chen JQ, Ren W, Qin L, Yates JL, Hunt DT, Lee WT, Crotty S, Krammer F, Grifoni A, Sette A, Simon V, and Coelho CH
- Subjects
- United States, Animals, Male, Female, Humans, Young Adult, Adult, Middle Aged, Leukocytes, Mononuclear, Vaccination, Monkeypox virus, Mpox (monkeypox) prevention & control, Smallpox Vaccine, Vaccines
- Abstract
Background: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity., Methods: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection., Findings: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6-33 days after the first dose and 5-40 days after the second dose. Mpox-convalescent samples were collected 20-102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20-102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4
+ and CD8+ T-cell responses., Interpretation: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans., Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine., Competing Interests: Declaration of interests FK has consulted for Curevac, Seqirus, and Merck; is currently consulting for Pfizer, Third Rock Ventures, Avimex, and GSK; and is named on several patents regarding influenza virus and SARS-CoV-2 vaccines, influenza virus therapeutics, and SARS-CoV-2 serological tests, some of which have been licensed to commercial entities, from which FK is receiving royalties. FK is also an advisory board member of Castlevax, a spin-off company formed by the Icahn School of Medicine at Mount Sinai to develop SARS-CoV-2 vaccines. FK's laboratory has received funding for research projects from Pfizer, GSK, and Dynavax, and three of FK's mentees have recently joined Moderna. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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4. Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review.
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Doernberg SB, Arias CA, Altman DR, Babiker A, Boucher HW, Creech CB, Cosgrove SE, Evans SR, Fowler VG, Fritz SA, Hamasaki T, Kelly BJ, Leal SM, Liu C, Lodise TP, Miller LG, Munita JM, Murray BE, Pettigrew MM, Ruffin F, Scheetz MH, Shopsin B, Tran TT, Turner NA, Williams DJ, Zaharoff S, and Holland TL
- Subjects
- Humans, Child, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Leadership, Quality of Life, Gram-Positive Bacteria, Methicillin-Resistant Staphylococcus aureus, Gram-Positive Bacterial Infections drug therapy, Gram-Positive Bacterial Infections microbiology, Sepsis drug therapy
- Abstract
The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections., Competing Interests: Potential conflicts of interest. All authors report funding support from the ARLG of the NIH and the NIAID (UM1AI104681). S. B. D. reports grants or contracts paid to her institution from Gilead, Pfizer, F2G, Regeneron, Chan Zuckerberg Biohub, and NIAID/NIH; consulting fees paid directly to her from Genentech and Janssen/Johnson & Johnson (J&J); travel and meeting support from the Infectious Diseases Society of America (IDSA) to speak at IDWeek; a patent (US20100143379A1) for Mif agonists and antagonist and therapeutic uses thereof; a leadership role on the IDSA Antibacterial Resistance Committee, California Department of Public Health Hospital Acquired Infections Advisory Committee, and ARLG Innovations Group, Laboratory Center, Mentorship Committee, Gram-positive Committee, and Immunosuppressed Host Group; and payment directly to her for clinical events committee/adjudication committee participation from Shionogi, Basilea, and the Duke Clinical Research Institute.D. R. A. reports funding support from ContraFect and a leadership role on the ARLG Gram-positive Committee. A. B. reports funding support from the ARLG Early Faculty Seedling Award (NIAID UM1AI104681) and consulting fees from Roche. H. W. B. reports royalties from the Sanford Guide; consulting fees from the Sanford Guide, Antimicrobial Agents and Chemotherapy/American Society for Microbiology (ASM), and ID Clinics of North America/Elsevier; honoraria for Grand Rounds at Temple University; travel and meeting support for an IDWeek Lecture; membership as a voting member on the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria; and membership on the Board of Trustees at the College of the Holy Cross. B. C. reports grants or contracts paid to his institution from Moderna Vaccines and Merck Vaccines; royalties from UpToDate; consulting fees from Cowen Investments, Pfizer, Moderna, GSK, and Sanofi; payment as a medicolegal expert with multiple law firms; participation on the data and safety monitoring board (DSMB) or advisory board for Affinivax and GSK; and a leadership role as president of the Pediatric Infectious Diseases Society. S. E. C. reports grants or contracts paid to her institution from the Agency for Healthcare Research and Quality (AHRQ), the Centers for Disease Control and Prevention (CDC), the Patient-Centered Outcomes Research Institute, and the US Food and Drug Administration (FDA); consulting fees paid directly to her from the Duke Clinical Research Institute; participation on a DSMB for Debiopharm; and leadership roles as a board member of the National Foundation for Infectious Diseases and Globarl Antibiotic Research and Development Partnership North America (GARDP-NA). S. R. E. reports grants from the NIAID/NIH and De Gruyter (Editor-in-Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, J&J, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute (IDDI), SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the FDA, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organizations of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; board member participation for the NIH, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, and Novartis; and board positions with the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the IDSA for his service as Associate Editor of Clinical Infectious Diseases; travel support from ContraFect to the 2019 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); and a sepsis diagnostics patent pending. S. A. F. reports grant or contracts from NIH (P50HD103525, U01AL116400, R21AI176063) and AHRQ (R01 HS024269), honoraria from ARLG, and provision of Clorox wipes for a clinical research study. B. J. K. reports grants from CDC and NIAID; honoraria from ARLG; and leadership roles in the CDC Microbiome Working Group, IDSA Journal Club, and ARLG. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma and honoraria from Duke University and Cancer and Chemo Therapy. T. P. L. reports grants paid to his institution from Wockhardt; grants paid directly to him from Paratek, Cidara, Biofire Diagnostics, and Merck; payment directly to him for lectures from Shionogi, Ferring, Seres, and Melinta; consulting fees paid directly to him from AbbVie, Cidara Therapeutics, Ferring, ICPD, Genentech, J&J, Melinta, Merck, Roche, Shionogi, Spero, Venatrox, La Jolla, Seres, Paratek, GSK, and DoseMe; and payment for the development of educational presentations from the Mayo Clinic. L. G. M. reports grants or contracts from Merck, ContraFect, Paratek, Medline, and GSK. J. M. M. reports grants from Asociación Nacional de Investigación y Desarrollo, Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT (grant number 1211947). B. S. reports advisory board fees paid directly to him from Basilia. T. T. T. reports grants from NIH paid to her institution; travel and meeting support from IDSA; and a leadership role on the IDWeek Planning Committee and a role as a Gulf Coast Consortium Cluster Reviewer (both unpaid). N. A. T. reports grants from CDC and PDI, Inc; and consulting fees from Techspert. D. J. W. reports grants paid to his institution from CDC and NIH/NIAID; a leadership role on the IDSA Childhood Pneumonia Guidelines Committee; and receipt of equipment from bioMérieux for procalcitonin assays for an observational study. T. L. H. reports grants from Karius and NIH; royalties from UpToDate; consulting fees from Aridis, Pfizer, Lysovant, and Affinivax; and participation on a DSMB for the SNAP Trial and the advisory board for Basilea. C. A. A. reports grant funding to their institution from NIH/NIAID (1 Po1 AI152999, R01AI148342, R01 AI346337, T32 AI141349, K24 Ai121296, U19 AI44297, R01 AI150685, and R21 AI151536), MeMed Diagnostics Ltd, Entasis Therapeutics, Merck Pharmaceuticals, and Harris County Public Health; royalties paid to them from UpToDate; reimbursement from IDSA for attending IDWeek as a speaker and part of the organizing committee; reimbursement from ASM to attend ASM Microbe as a speaker; reimbursement from the Society for Healthcare Epidemiology of America (SHEA) to attend SHEA as a speaker; reimbursement from the European Society for Clinical Microbiology and Infectious Diseases to attend ECCMID as a speaker; reimbursement from Mérieux Foundation to attend ICARE course as faculty; reimbursement from Sociedad Chilea de Infectiologia, Sociedad Colombiana de Infectologia, Pan American Society for Infectious Diseases, and Brazilian Society for Infectious Diseases to attend the annual meeting and act as a speaker; was an unpaid participant on a DSMB with the World Health Organization and Antibacterial Pipeline Advisory Group; received payment for participation with the NIH Grant Review Study Sections; was a voluntary member of the board of directors of IDSA; and is the Editor-in-Chief of Antimicrobial Agents and Chemotherapy. B. E. M. reports royalties from UpToDate for online chapters; consulting fees from JRD, LLC (J&J), PPD Development, LP (GSK0 and Basilea Pharmaceutical International Ltd); participation on a DSMB with NIH Therapeutic and Prevention; and held the position of Governor of the Academy with the American Academy of Microbiology. C. L. reports grant payments to their institutions from NIAID/NIH (1R01AI151038-01) and Pfizer. M. H. S. reports advisory board fees from DoseMe; consulting fees from GSK and Entasis; and has an issued patent US10688195B2. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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5. Methicillin-resistant Staphylococcus aureus bacteremia with elevated vancomycin minimum inhibitory concentrations.
- Author
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Mills AG, Dupper AC, Chacko KI, Alburquerque B, Nadkarni D, Berbel Caban A, Fox L, Gitman MR, Obla A, van Bakel H, and Altman DR
- Abstract
This case-control study of 25 cases with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with vancomycin minimum inhibitory concentration (MIC) ≥ 2 µg/mL and 391 controls (MIC < 2 µg/mL) characterized the clinical characteristics, treatments, and outcomes associated with elevated vancomycin MIC. Elevated vancomycin MIC was associated with baseline hemodialysis, prior MRSA colonization, and metastatic infection., Competing Interests: Dr. Altman has received institutional funding from participation in ContraFect corporation clinical trials. The other authors have no financial or other conflicts of interest to disclose., (© The Author(s) 2023.)
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- 2023
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6. MRSA lineage USA300 isolated from bloodstream infections exhibit altered virulence regulation.
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Dyzenhaus S, Sullivan MJ, Alburquerque B, Boff D, van de Guchte A, Chung M, Fulmer Y, Copin R, Ilmain JK, O'Keefe A, Altman DR, Stubbe FX, Podkowik M, Dupper AC, Shopsin B, van Bakel H, and Torres VJ
- Subjects
- Animals, Mice, Virulence genetics, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections, Cross Infection epidemiology, Sepsis
- Abstract
The epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 lineage has recently become a leading cause of hospital-associated bloodstream infections (BSIs). Here, we leveraged this recent introduction into hospitals and the limited genetic variation across USA300 isolates to identify mutations that contribute to its success in a new environment. We found that USA300 BSI isolates exhibit altered virulence regulation. Using comparative genomics to delineate the genes involved in this phenotype, we discovered repeated and independent mutations in the transcriptional regulator sarZ. Mutations in sarZ resulted in increased virulence of USA300 BSI isolates in a murine model of BSI. The sarZ mutations derepressed the expression and production of the surface protein ClfB, which was critical for the pathogenesis of USA300 BSI isolates. Altogether, these findings highlight ongoing evolution of a major MRSA lineage and suggest USA300 strains can optimize their fitness through altered regulation of virulence., Competing Interests: Declaration of interests V.J.T. is an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. provides research funding and other payments associated with a licensing agreement., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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7. Everybody nose: molecular and clinical characteristics of nasal colonization during active methicillin-resistant Staphylococcus aureus bloodstream infection.
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Reategui Schwarz E, van de Guchte A, Dupper AC, Caban AB, Nadkarni D, Fox L, Mills A, Obla A, Chacko KI, Oussenko I, Samaroo F, Polanco J, Silvera R, Smith ML, Patel G, Gitman M, Alburquerque B, Chung M, Sullivan MJ, van Bakel H, and Altman DR
- Subjects
- Carrier State, Humans, Male, Nose, Retrospective Studies, Staphylococcus aureus, Bacteremia epidemiology, Cross Infection epidemiology, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
Background: Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization., Methods: Swabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A (spa) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models., Results: Over an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 213 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization., Conclusion: The molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease., (© 2022. The Author(s).)
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- 2022
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8. Modified methicillin-resistant Staphylococcus aureus detected in neonatal intensive care patients.
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Gitman MR, Alburquerque B, Chung M, van de Guchte A, Sullivan MJ, Obla A, Polanco J, Oussenko I, Smith ML, Samaroo F, Barackman D, Altman DR, Sordillo EM, and van Bakel H
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacterial Proteins, Humans, Infant, Newborn, Intensive Care, Neonatal, Microbial Sensitivity Tests, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections drug therapy, Staphylococcal Infections epidemiology
- Abstract
Objectives: As part of an active MRSA surveillance programme in our neonatal ICU, we identified nares surveillance cultures from two infants that displayed heterogeneity in methicillin resistance between isolated subclones that lacked mecA and mecC., Methods: The underlying mechanism for the modified Staphylococcus aureus (MODSA) methicillin-resistance phenotype was investigated by WGS., Results: Comparison of finished-quality genomes of four MODSA and four MSSA subclones demonstrated that the resistance changes were associated with unique truncating mutations in the gene encoding the cyclic diadenosine monophosphate phosphodiesterase enzyme GdpP or a non-synonymous substitution in the gene encoding PBP2., Conclusions: These two cases highlight the difficulty in identifying non-mecA, non-mecC-mediated MRSA isolates in the clinical microbiology laboratory, which leads to difficulties in implementing appropriate therapy and infection control measures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
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- 2021
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9. Demographic Characteristics of Adults with IgG Antibodies to Prior Symptomatic SARS-CoV-2 Infection.
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Mansour M, Wajnberg A, Altman DR, Muellers K, and Stone K
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- Adult, Antibodies, Viral, Demography, Humans, Immunoglobulin G, COVID-19, SARS-CoV-2
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- 2021
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10. Associations between weight-based teasing and disordered eating behaviors among youth.
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Rubin AG, Schvey NA, Shank LM, Altman DR, Swanson TN, Ramirez E, Moore NA, Jaramillo M, Ramirez S, Davis EK, Broadney MM, LeMay-Russell S, Byrne ME, Parker MK, Brady SM, Kelly NR, Tanofsky-Kraff M, and Yanovski JA
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- Adiposity, Adolescent, Body Weight, Feeding Behavior, Female, Humans, Male, Obesity, Overweight, Feeding and Eating Disorders
- Abstract
Weight-based teasing (WBT) is commonly reported among youth and is associated with disinhibited and disordered eating. Specifically, youth who experience WBT may engage in disordered eating behaviors to cope with the resultant negative affect. Therefore, we examined associations between WBT and disordered eating behaviors among youth and assessed whether negative affect mediated these relationships. Two hundred one non-treatment seeking youth (8-17y) completed questionnaires assessing WBT, disinhibited eating, depression, and anxiety. Disordered eating and loss-of-control (LOC) eating were assessed via semi-structured interview. Analyses of covariance were conducted to examine relationships between WBT and eating-related variables, and bootstrapping mediation models were used to evaluate negative affect (a composite of depressive and anxiety symptoms) as a mediator of these associations. All models were adjusted for sex, race, age, and adiposity. Among 201 participants (13.1 ± 2.8y; 54.2% female; 30.3% Black; 32.8% with overweight/obesity), WBT was associated with emotional eating, eating in the absence of hunger, and disordered eating attitudes and behaviors (ps ≤ 0.02). These associations were all mediated by negative affect. WBT was also associated with a threefold greater likelihood of reporting a recent LOC eating episode (p = .049). Among boys and girls across weight strata, WBT was associated with multiple aspects of disordered eating and these relationships were mediated by negative affect. Longitudinal studies are needed to clarify the directionality of these associations and to identify subgroups of youth that may be particularly vulnerable to WBT and its sequelae., (Published by Elsevier Ltd.)
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- 2021
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11. Weight-based teasing in youth: Associations with metabolic and inflammatory markers.
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Schvey NA, Shank LM, Tanofsky-Kraff M, Ramirez S, Altman DR, Swanson T, Rubin AG, Kelly NR, LeMay-Russell S, Byrne ME, Parker MN, Broadney MM, Brady SM, Yanovski SZ, and Yanovski JA
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- Adolescent, Biomarkers blood, Blood Glucose, Blood Sedimentation, C-Reactive Protein analysis, Cardiometabolic Risk Factors, Child, Cholesterol, HDL blood, Fasting blood, Female, Humans, Longitudinal Studies, Male, Pediatric Obesity therapy, Triglycerides blood, Pediatric Obesity blood, Pediatric Obesity psychology, Weight Prejudice statistics & numerical data
- Abstract
Background: Research among adults suggests that weight stigma is associated with worsened cardiometabolic health. However, these relationships have not been examined among youth., Objective: Assess associations between weight-based teasing (WBT) and metabolic and inflammatory markers among two samples of youth: (1) a non-treatment-seeking sample and (2) a weight loss treatment-seeking sample with obesity., Method: Weight, height, adiposity, waist circumference and blood pressure were measured. Fasting blood samples were collected for metabolic (triglycerides, glucose, high-density lipoprotein cholesterol) and inflammatory analytes (high-sensitivity C-reactive protein in Study 1 and erythrocyte sedimentation rate in both studies). Youths completed the Perception of Teasing Scale, a measure of WBT. Metabolic and inflammatory indices were compared between those with and without teasing, adjusting for demographics and body composition., Results: Study 1 enrolled 201 non-treatment-seeking youth (M
age = 13.1y; 54.2% female; 44.8% non-Hispanic White; 32.8% with overweight/obesity); 15.4% reported WBT. Study 2 enrolled 111 treatment-seeking adolescents with obesity (Mage = 14.0y; 66.7% female; 37.8% non-Hispanic White); 73.0% reported WBT. Adjusting for covariates, WBT was not associated with cardiometabolic risk factors in either study., Conclusions: WBT was not associated with worsened cardiometabolic health. Longitudinal research is needed to elucidate associations between WBT and health in youth., (© 2020 World Obesity Federation.)- Published
- 2021
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12. Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19.
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Mazori AY, Bass IR, Chan L, Mathews KS, Altman DR, Saha A, Soh H, Wen HH, Bose S, Leven E, Wang JG, Mosoyan G, Pattharanitima P, Greco G, and Gallagher EJ
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- Blood Glucose, Critical Illness, Hospital Mortality, Humans, Intensive Care Units, Retrospective Studies, SARS-CoV-2, COVID-19, Hyperglycemia epidemiology
- Abstract
Objective: To explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19)., Methods: The study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate., Results: Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023)., Conclusion: Among critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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13. Inhibitory control and negative affect in relation to food intake among youth.
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Byrne ME, Shank LM, Altman DR, Swanson TN, Ramirez E, Moore NA, Rubin SG, LeMay-Russell S, Parker MN, Kaufman RE, Yang SB, Torres SL, Brady SM, Kelly NR, Tanofsky-Kraff M, and Yanovski JA
- Subjects
- Adolescent, Cross-Sectional Studies, Eating, Energy Intake, Female, Humans, Hyperphagia, Male, Feeding Behavior, Snacks
- Abstract
Negative affect and poor inhibitory control are related to disinhibited eating behaviors in youth and may contribute to the development and/or maintenance of obesity. Although few studies have jointly examined these constructs in youth, it has been theorized that poor inhibitory control may be driven by negative affect. If supported, impaired inhibitory control, driven by negative affect, could represent a modifiable neurocognitive treatment target for disinhibited eating. The current study examined whether inhibitory control mediates the relationship between negative affect and eating among youth. Youth (8-17 years) participated in a Food Go/No-Go neurocognitive task to measure inhibitory control as the percentage of commission errors. A composite negative affect score was created from self-report measures of anxiety and depression. A laboratory buffet meal modeled to simulate disinhibited eating was used to measure total and snack food intake. Cross-sectional mediation models with bias-corrected bootstrap confidence intervals (CI) were conducted using negative affect as the independent variable, inhibitory control as the mediator, and intake patterns as dependent variables. One-hundred-eighty-one youths (13.2 ± 2.7y; 55% female; BMIz 0.6 ± 1.0) were studied. Total Go/No-Go commission errors mediated the relationship between negative affect and total intake (95%CI = [0.3, 31.6]), but not snack intake (95%CI = [-2.5, 7.3]). Commission errors for Food-Go blocks significantly mediated the relationship between negative affect and total intake (95%CI = [7.7, 44.4]), but not snack intake (95%CI = [-3.4, 9.5]). Commission errors on Neutral-Go blocks did not significantly mediate any of these relationships. Negative affect may lead to poorer inhibitory control as well as a stronger approach tendency toward food, increasing the likelihood of engaging in disinhibited eating. Future research should determine if, in combination with approaches to reduce negative affect, improved inhibitory control could help prevent overeating in youths with depressive or anxiety symptoms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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14. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.
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Wajnberg A, Amanat F, Firpo A, Altman DR, Bailey MJ, Mansour M, McMahon M, Meade P, Mendu DR, Muellers K, Stadlbauer D, Stone K, Strohmeier S, Simon V, Aberg J, Reich DL, Krammer F, and Cordon-Cardo C
- Subjects
- Antibodies, Neutralizing blood, Antibodies, Viral blood, COVID-19 blood, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Neutralization Tests, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, SARS-CoV-2 immunology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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- 2020
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15. PathoSPOT genomic epidemiology reveals under-the-radar nosocomial outbreaks.
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Berbel Caban A, Pak TR, Obla A, Dupper AC, Chacko KI, Fox L, Mills A, Ciferri B, Oussenko I, Beckford C, Chung M, Sebra R, Smith M, Conolly S, Patel G, Kasarskis A, Sullivan MJ, Altman DR, and van Bakel H
- Subjects
- Adolescent, Adult, Aged, Bacteremia microbiology, Cross Infection microbiology, Cross Infection prevention & control, Cross Infection transmission, Female, Genome, Bacterial, Hospitals, Humans, Male, Methicillin-Resistant Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus isolation & purification, Middle Aged, Phylogeny, Staphylococcal Infections epidemiology, Staphylococcal Infections transmission, Whole Genome Sequencing, Young Adult, Cross Infection epidemiology, Disease Outbreaks prevention & control, Genomics, Molecular Epidemiology
- Abstract
Background: Whole-genome sequencing (WGS) is increasingly used to map the spread of bacterial and viral pathogens in nosocomial settings. A limiting factor for more widespread adoption of WGS for hospital infection prevention practices is the availability of standardized tools for genomic epidemiology., Methods: We developed the Pathogen Sequencing Phylogenomic Outbreak Toolkit (PathoSPOT) to automate integration of genomic and medical record data for rapid detection and tracing of nosocomial outbreaks. To demonstrate its capabilities, we applied PathoSPOT to complete genome surveillance data of 197 MRSA bacteremia cases from two hospitals during a 2-year period., Results: PathoSPOT identified 8 clonal clusters encompassing 33 patients (16.8% of cases), none of which had been recognized by standard practices. The largest cluster corresponded to a prolonged outbreak of a hospital-associated MRSA clone among 16 adults, spanning 9 wards over a period of 21 months. Analysis of precise timeline and location data with our toolkit suggested that an initial exposure event in a single ward led to infection and long-term colonization of multiple patients, followed by transmissions to other patients during recurrent hospitalizations., Conclusions: We demonstrate that PathoSPOT genomic surveillance enables the detection of complex transmission chains that are not readily apparent from epidemiological data and that contribute significantly to morbidity and mortality, enabling more effective intervention strategies.
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- 2020
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16. Staphylococcus aureus Bacteremia in Patients Infected With COVID-19: A Case Series.
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Cusumano JA, Dupper AC, Malik Y, Gavioli EM, Banga J, Berbel Caban A, Nadkarni D, Obla A, Vasa CV, Mazo D, and Altman DR
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Background: Previous viral pandemics have shown that secondary bacterial infections result in higher morbidity and mortality, with Staphylococcus aureus being the primary causative pathogen. The impact of secondary S. aureus bacteremia on mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unknown., Methods: This was a retrospective observational case series of patients with coronavirus disease 2019 (COVID-19) who developed secondary S. aureus bacteremia across 2 New York City hospitals. The primary end point was to describe 14-day and 30-day hospital mortality rates of patients with COVID-19 and S. aureus bacteremia. Secondary end points included predictors of 14-day and 30-day hospital mortality in patients with COVID-19 and S. aureus bacteremia., Results: A total of 42 patients hospitalized for COVID-19 with secondary S. aureus bacteremia were identified. Of these patients, 23 (54.8%) and 28 (66.7%) died at 14 days and 30 days, respectively, from their first positive blood culture. Multivariate analysis identified hospital-onset bacteremia (≥4 days from date of admission) and age as significant predictors of 14-day hospital mortality and Pitt bacteremia score as a significant predictor of 30-day hospital mortality (odds ratio [OR], 11.9; 95% CI, 2.03-114.7; P = .01; OR, 1.10; 95% CI, 1.03-1.20; P = .02; and OR, 1.56; 95% CI, 1.19-2.18; P = .003, respectively)., Conclusions: Bacteremia with S. aureus is associated with high mortality rates in patients hospitalized with COVID-19. Further investigation is warranted to understand the impact of COVID-19 and secondary S. aureus bacteremia., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2020
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17. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study.
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Liu STH, Lin HM, Baine I, Wajnberg A, Gumprecht JP, Rahman F, Rodriguez D, Tandon P, Bassily-Marcus A, Bander J, Sanky C, Dupper A, Zheng A, Nguyen FT, Amanat F, Stadlbauer D, Altman DR, Chen BK, Krammer F, Mendu DR, Firpo-Betancourt A, Levin MA, Bagiella E, Casadevall A, Cordon-Cardo C, Jhang JS, Arinsburg SA, Reich DL, Aberg JA, and Bouvier NM
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- Adult, Aged, Antibodies, Viral blood, COVID-19 epidemiology, Case-Control Studies, Female, Humans, Immunization, Passive, Male, Middle Aged, Pandemics, Propensity Score, Retrospective Studies, SARS-CoV-2 immunology, Severity of Illness Index, Treatment Outcome, COVID-19 Serotherapy, COVID-19 pathology, COVID-19 therapy
- Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments
1 . Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses2,3 . Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed1,2 . This retrospective, propensity score-matched case-control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score-matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75-0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13-0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed.- Published
- 2020
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18. Introductions and early spread of SARS-CoV-2 in the New York City area.
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Gonzalez-Reiche AS, Hernandez MM, Sullivan MJ, Ciferri B, Alshammary H, Obla A, Fabre S, Kleiner G, Polanco J, Khan Z, Alburquerque B, van de Guchte A, Dutta J, Francoeur N, Melo BS, Oussenko I, Deikus G, Soto J, Sridhar SH, Wang YC, Twyman K, Kasarskis A, Altman DR, Smith M, Sebra R, Aberg J, Krammer F, García-Sastre A, Luksza M, Patel G, Paniz-Mondolfi A, Gitman M, Sordillo EM, Simon V, and van Bakel H
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- Adult, Aged, Aged, 80 and over, COVID-19, Coronavirus Infections mortality, Epidemiological Monitoring, Female, Geography, Medical, Humans, Male, Middle Aged, New York City epidemiology, Pandemics, Phylogeny, Pneumonia, Viral mortality, Residence Characteristics, SARS-CoV-2, Young Adult, Betacoronavirus genetics, Coronavirus Infections epidemiology, Coronavirus Infections transmission, Genome, Viral, Pneumonia, Viral epidemiology, Pneumonia, Viral transmission
- Abstract
New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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- 2020
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19. Executive functioning and disinhibited eating in children and adolescents.
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Kelly NR, Jaramillo M, Ramirez S, Altman DR, Rubin SG, Yang SB, Courville AB, Shank LM, Byrne ME, Lemay-Russell S, Brady SM, Broadney MM, Tanofsky-Kraff M, and Yanovski JA
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- Adolescent, Adolescent Behavior, Child, Cognition, Decision Making, Energy Intake, Female, Humans, Male, Executive Function physiology, Feeding Behavior psychology
- Abstract
Background: Executive functioning (EF) difficulties may be associated with problems regulating eating behaviours. Few studies have evaluated this question in youth using diverse measures of EF or objective measures of energy intake., Methods: The current study used neuropsychological tasks and a laboratory test meal to evaluate the links between EF and youth's disinhibited eating patterns. Two-hundred-five nontreatment seeking youth (M age = 13.1 ± 2.8 years; M BMIz = 0.6 ± 1.0; 33.2% overweight; 54.1% female) completed tasks measuring decision making, general and food-specific behavioural disinhibition, willingness to delay gratification for food and money, cognitive flexibility, and working memory. Age (children vs adolescents) was examined as a moderator. All analyses adjusted for demographic factors, pubertal status, lean mass (kg), fat mass (%), height, general intellectual functioning, and depressive symptoms., Results: After adjusting for multiple comparisons, more general behavioural disinhibition was associated with greater total energy intake (P = .02), and poorer cognitive flexibility was associated with more fat intake (P = .03) across all ages. Poorer decision making in children (P = .04), but not adolescents (P = .24), was associated with greater fat intake. Food-specific behavioural disinhibition, the ability to delay gratification for both food and monetary rewards, and working memory were not significantly associated with youth's disinhibited eating patterns during a single meal., Conclusions: Most domains of EF were not associated with youth's disinhibited eating. Significant associations may highlight the need to target specific cognitive processes, particularly behavioural disinhibition, decision making, and cognitive flexibility, in potential intervention strategies for children's disinhibited eating., (© 2020 World Obesity Federation.)
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- 2020
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20. Assessment of loss-of-control eating in healthy youth by interview and questionnaire.
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Altman DR, Tanofsky-Kraff M, Shank LM, Swanson TN, Ramirez E, Moore NA, Rubin SG, Byrne ME, LeMay-Russell S, Schvey NA, Kelly NR, Parker MN, Gubbi S, Brady SM, Yanovski SZ, and Yanovski JA
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- Adolescent, Female, Humans, Interview, Psychological, Male, Reproducibility of Results, Surveys and Questionnaires, Feeding Behavior psychology, Feeding and Eating Disorders complications, Psychometrics methods
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Objective: The aim of this study is to evaluate two questionnaires, an updated youth version of the questionnaire on eating and weight patterns (Questionnaire on Eating and Weight Patterns-5 Children/Adolescent [QEWP-C-5]) and the Loss-of-Control (LOC) Eating Disorder Questionnaire (LOC-ED-Q), against the Eating Disorder Examination (EDE) interview to assess the presence of LOC-eating among youth., Method: Two-hundred and eighteen youths (12.8 ± 2.7 years) completed the QEWP-C-5, LOC-ED-Q, and EDE, depressive and anxiety questionnaires, and adiposity assessment. Sensitivity, specificity, positive-predictive value, negative-predictive value, and diagnostic accuracy were calculated; Cochran's Q and McNemar's tests were used to compare measures. Receiver operating characteristic area under the curve (AUC) analyses were performed. Mood and adiposity based on LOC-eating presence and absence based on each measure were examined., Results: The QEWP-C-5 and LOC-ED-Q demonstrated poor sensitivity (33%; 30%) and high specificity (95%; 96%) compared with the EDE. The AUCs suggested neither the QEWP-C-5 (0.64) nor the LOC-ED-Q (0.62) demonstrated acceptable diagnostic accuracy. Comparing distributions of LOC-eating presence between assessments, the QEWP-C-5 and EDE did not differ significantly (p = .10), while the LOC-ED-Q and EDE had significantly different distributions (p = .03). LOC-eating presence was associated with higher depressive and anxiety symptoms across all measures (ps < .02). Greater adiposity (ps < .02) was associated with LOC-eating presence on the EDE and LOC-ED-Q, and higher BMI z-score (p = .02) on the LOC-ED-Q., Discussion: Neither the QEWP-C-5 nor the LOC-ED-Q was sensitive for identifying LOC-eating presence as determined by the EDE, although both were associated with greater mood symptoms. Research is needed to improve self-report questionnaires to better screen for LOC-eating presence among pediatric populations., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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21. Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis.
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Oliveira PH, Ribis JW, Garrett EM, Trzilova D, Kim A, Sekulovic O, Mead EA, Pak T, Zhu S, Deikus G, Touchon M, Lewis-Sandari M, Beckford C, Zeitouni NE, Altman DR, Webster E, Oussenko I, Bunyavanich S, Aggarwal AK, Bashir A, Patel G, Wallach F, Hamula C, Huprikar S, Schadt EE, Sebra R, van Bakel H, Kasarskis A, Tamayo R, Shen A, and Fang G
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- Animals, Bacterial Proteins genetics, Bacterial Proteins metabolism, Clostridioides difficile genetics, Clostridium Infections microbiology, Cricetinae, DNA Methylation, DNA Modification Methylases genetics, DNA, Bacterial genetics, DNA, Bacterial metabolism, Epigenome, Gene Expression Regulation, Bacterial, Genetic Variation, Genome, Bacterial genetics, Humans, Mice, Mutation, Nucleotide Motifs, Phylogeny, Regulatory Elements, Transcriptional genetics, Spores, Bacterial genetics, Spores, Bacterial physiology, Substrate Specificity, Clostridioides difficile enzymology, Clostridioides difficile pathogenicity, Clostridioides difficile physiology, DNA Modification Methylases metabolism, Epigenesis, Genetic
- Abstract
Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored. Here, we perform a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high level of epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity, the corresponding gene of which is highly conserved across our dataset and in all of the approximately 300 global C. difficile genomes examined. Inactivation of the methyltransferase gene negatively impacts sporulation, a key step in C. difficile disease transmission, and these results are consistently supported by multiomics data, genetic experiments and a mouse colonization model. Further experimental and transcriptomic analyses suggest that epigenetic regulation is associated with cell length, biofilm formation and host colonization. These findings provide a unique epigenetic dimension to characterize medically relevant biological processes in this important pathogen. This study also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomic studies.
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- 2020
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22. A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak.
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Sullivan MJ, Altman DR, Chacko KI, Ciferri B, Webster E, Pak TR, Deikus G, Lewis-Sandari M, Khan Z, Beckford C, Rendo A, Samaroo F, Sebra R, Karam-Howlin R, Dingle T, Hamula C, Bashir A, Schadt E, Patel G, Wallach F, Kasarskis A, Gibbs K, and van Bakel H
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- Adult, Bacteremia microbiology, Bacteremia transmission, Cross Infection microbiology, Cross Infection transmission, Disease Transmission, Infectious, Genotype, Hospitals, Humans, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Mass Screening methods, Methicillin-Resistant Staphylococcus aureus classification, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections microbiology, Staphylococcal Infections transmission, Bacteremia epidemiology, Cross Infection epidemiology, Disease Outbreaks, Methicillin-Resistant Staphylococcus aureus isolation & purification, Molecular Epidemiology methods, Staphylococcal Infections epidemiology, Whole Genome Sequencing methods
- Abstract
Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence., (Copyright © 2019 Sullivan et al.)
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- 2019
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23. The association between alexithymia and eating behavior in children and adolescents.
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Shank LM, Tanofsky-Kraff M, Kelly NR, Jaramillo M, Rubin SG, Altman DR, Byrne ME, LeMay-Russell S, Schvey NA, Broadney MM, Brady SM, Yang SB, Courville AB, Ramirez S, Crist AC, Yanovski SZ, and Yanovski JA
- Subjects
- Adolescent, Body Weight, Child, Emotions, Feeding and Eating Disorders psychology, Female, Humans, Hunger, Male, Adolescent Behavior psychology, Affective Symptoms psychology, Child Behavior psychology, Eating psychology, Feeding Behavior psychology
- Abstract
Objective: Alexithymia, or the difficulty identifying or describing one's own emotions, may be a risk factor for dysregulated eating and excess weight gain. However, the relationships between alexithymia and eating behaviors in community samples of non-clinical youth have not been well-characterized. We hypothesized that alexithymia would be positively associated with disordered and disinhibited eating in a community-based sample of boys and girls without an eating disorder., Method: Two hundred children (8-17 years old) across the weight spectrum completed an interview to assess loss of control (LOC) eating and eating-related psychopathology, a laboratory test meal designed to induce disinhibited eating, and questionnaires to assess alexithymia, eating in the absence of hunger, and emotional eating. Linear and logistic regressions were conducted to examine the relationship between alexithymia and eating variables, with age, sex, race, and fat mass as covariates. Test meal analyses also adjusted for lean mass. Given the overlap between alexithymia and depression, all models were repeated with depressive symptoms as an additional covariate., Results: Alexithymia was associated with an increased likelihood of reporting LOC eating (p < .05). Moreover, alexithymia was positively associated with disordered eating attitudes, emotional eating, and eating in the absence of hunger (ps < .05). Greater alexithymia was associated with more carbohydrate and less fat intake at the test meal (ps < .05). After adjusting for depressive symptoms, alexithymia remained associated with eating in the absence of hunger and carbohydrate and fat intake (ps < .05)., Discussion: In healthy children, alexithymia is associated with some facets of eating behavior and food intake. If supported prospectively, these preliminary findings suggest alexithymia may be a modifiable risk factor to reduce disordered eating and excess weight gain in youth., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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24. Relationships of Trait Anxiety and Loss of Control Eating with Serum Leptin Concentrations among Youth.
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Byrne ME, Tanofsky-Kraff M, Jaramillo M, Shank LM, LeMay-Russell S, Rubin SG, Ramirez S, Altman DR, Schvey NA, Brady SM, Shomaker LB, Courville AB, Yang SB, Kozlosky M, Broadney MM, Yanovski SZ, and Yanovski JA
- Subjects
- Adiposity, Adolescent, Body Mass Index, Child, Fasting blood, Feeding Behavior psychology, Female, Humans, Linear Models, Male, Anxiety blood, Anxiety psychology, Feeding and Eating Disorders blood, Feeding and Eating Disorders psychology, Leptin blood
- Abstract
Loss of control (LOC) eating in youth is associated with elevated fasting serum leptin, even after accounting for adiposity. Anxiety is closely linked to, and may exacerbate, LOC eating. Yet, it remains unclear how anxiety relates to leptin, or if the relationship is moderated by the presence of LOC eating. We examined whether self-reported trait anxiety interacted with LOC eating in relation to leptin in a convenience sample of youths ( n = 592; 13.1 ± 2.7 years; body mass index z -score (BMI z ) = 0.9 ± 1.1; 61.8% girls; 53.5% non-Hispanic White; 36.6% with LOC eating). LOC eating was assessed by interview. Leptin was measured after an overnight fast. Exploratory analyses were conducted to examine anxiety and LOC eating in relation to laboratory intake patterns in three sub-samples. In a generalized linear model adjusting for relevant covariates, anxiety significantly interacted with LOC eating in relation to leptin ( p = 0.02), such that greater trait anxiety related to higher concentrations of leptin only among youth with LOC eating. Trait anxiety was not significantly related to fasting serum leptin independently in a generalized linear model adjusting for age, race, height, sex, study type, and fat mass (kg). Exploratory mechanistic analyses of food intake patterns did not identify consistent results for participants with both anxiety and LOC eating. Among youth with LOC eating, anxiety may be associated with higher serum leptin. Prospective data are required to elucidate the directionality and mechanisms of these relationships.
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- 2019
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25. Associations of Weekday and Weekend Sleep with Children's Reported Eating in the Absence of Hunger.
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LeMay-Russell S, Tanofsky-Kraff M, Schvey NA, Kelly NR, Shank LM, Mi SJ, Jaramillo M, Ramirez S, Altman DR, Rubin SG, Byrne ME, Burke NL, Davis EK, Broadney MM, Brady SM, Yanovski SZ, and Yanovski JA
- Subjects
- Adiposity, Adolescent, Child, Data Collection, Feeding Behavior, Female, Humans, Male, Time Factors, Eating, Hunger, Sleep
- Abstract
Insufficient average sleep duration has been inconsistently associated with poor diet and obesity risks in youth. Inconsistencies in findings across studies may be due to a general failure to examine associations in weekday versus weekend sleep. We hypothesized that greater variations in weekday and weekend sleep duration would be associated with more disinhibited eating behaviors, which, in turn, might be involved in the relationship between sleep and weight. We, therefore, examined, among healthy, non-treatment seeking youth, the associations of average weekly, weekend, and weekday sleep duration with eating in the absence of hunger (EAH), a disinhibited eating behavior associated with disordered eating and obesity. Sleep was assessed via actigraphy for 14 days. Participants completed a self-report measure of EAH. Adiposity was measured by dual-energy X-ray absorptiometry. Linear regressions were used to test the associations of sleep duration with EAH and the associations of sleep duration and EAH, with fat mass. Among 123 participants (8-17 years, 52.0% female, and 30.9% with overweight), there was no significant association between average weekly sleep and EAH. Further, there was no significant association among average weekly sleep duration or EAH and fat mass. However, average weekday sleep was negatively associated, and average weekend sleep was positively associated, with EAH ( p s < 0.02). Weekend "catch-up" sleep (the difference between weekend and weekday sleep) was positively associated with EAH ( p < 0.01). Findings indicate that shorter weekday sleep and greater weekend "catch-up" sleep are associated with EAH, which may place youth at risk for the development of excess weight gain over time.
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- 2019
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26. Blurred Molecular Epidemiological Lines Between the Two Dominant Methicillin-Resistant Staphylococcus aureus Clones.
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Dupper AC, Sullivan MJ, Chacko KI, Mishkin A, Ciferri B, Kumaresh A, Berbel Caban A, Oussenko I, Beckford C, Zeitouni NE, Sebra R, Hamula C, Smith M, Kasarskis A, Patel G, McBride RB, van Bakel H, and Altman DR
- Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of health care-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones., Methods: Comprehensive clinical data from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones were compared using logistic regression., Results: Molecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (n = 117) and CC8 (n = 110). MRSA BSIs were associated with a 90-day mortality rate of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; P < .001) and in those of nonwhite race (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.51-7.87; P = .003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR, 5.96; 95% CI, 1.51-23.50; P = .01)., Conclusions: The clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen are crucial to inform management and prevent disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2019
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27. Sequential evolution of virulence and resistance during clonal spread of community-acquired methicillin-resistant Staphylococcus aureus .
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Copin R, Sause WE, Fulmer Y, Balasubramanian D, Dyzenhaus S, Ahmed JM, Kumar K, Lees J, Stachel A, Fisher JC, Drlica K, Phillips M, Weiser JN, Planet PJ, Uhlemann AC, Altman DR, Sebra R, van Bakel H, Lighter J, Torres VJ, and Shopsin B
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Child, Chlorhexidine pharmacology, Community-Acquired Infections drug therapy, Genome, Bacterial genetics, Humans, Methicillin-Resistant Staphylococcus aureus drug effects, Mice, Microbial Sensitivity Tests methods, Mupirocin pharmacology, Phylogeny, Plasmids genetics, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Community-Acquired Infections microbiology, Methicillin-Resistant Staphylococcus aureus genetics, Virulence genetics
- Abstract
The past two decades have witnessed an alarming expansion of staphylococcal disease caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The factors underlying the epidemic expansion of CA-MRSA lineages such as USA300, the predominant CA-MRSA clone in the United States, are largely unknown. Previously described virulence and antimicrobial resistance genes that promote the dissemination of CA-MRSA are carried by mobile genetic elements, including phages and plasmids. Here, we used high-resolution genomics and experimental infections to characterize the evolution of a USA300 variant plaguing a patient population at increased risk of infection to understand the mechanisms underlying the emergence of genetic elements that facilitate clonal spread of the pathogen. Genetic analyses provided conclusive evidence that fitness (manifest as emergence of a dominant clone) changed coincidently with the stepwise emergence of ( i ) a unique prophage and mutation of the regulator of the pyrimidine nucleotide biosynthetic operon that promoted abscess formation and colonization, respectively, thereby priming the clone for success; and ( ii ) a unique plasmid that conferred resistance to two topical microbiocides, mupirocin and chlorhexidine, frequently used for decolonization and infection prevention. The resistance plasmid evolved through successive incorporation of DNA elements from non- S. aureus spp. into an indigenous cryptic plasmid, suggesting a mechanism for interspecies genetic exchange that promotes antimicrobial resistance. Collectively, the data suggest that clonal spread in a vulnerable population resulted from extensive clinical intervention and intense selection pressure toward a pathogen lifestyle that involved the evolution of consequential mutations and mobile genetic elements., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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28. Genome Plasticity of agr -Defective Staphylococcus aureus during Clinical Infection.
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Altman DR, Sullivan MJ, Chacko KI, Balasubramanian D, Pak TR, Sause WE, Kumar K, Sebra R, Deikus G, Attie O, Rose H, Lewis M, Fulmer Y, Bashir A, Kasarskis A, Schadt EE, Richardson AR, Torres VJ, Shopsin B, and van Bakel H
- Subjects
- Animals, Bacteremia microbiology, Bacterial Proteins metabolism, Female, Gene Expression Regulation, Bacterial, Humans, Mice, Mutation, Phylogeny, Staphylococcus aureus classification, Staphylococcus aureus pathogenicity, Trans-Activators metabolism, Virulence, Bacterial Proteins genetics, Genome, Bacterial, Staphylococcal Infections microbiology, Staphylococcus aureus genetics, Staphylococcus aureus metabolism, Trans-Activators genetics
- Abstract
Therapy for bacteremia caused by Staphylococcus aureus is often ineffective, even when treatment conditions are optimal according to experimental protocols. Adapted subclones, such as those bearing mutations that attenuate agr -mediated virulence activation, are associated with persistent infection and patient mortality. To identify additional alterations in agr -defective mutants, we sequenced and assembled the complete genomes of clone pairs from colonizing and infected sites of several patients in whom S. aureus demonstrated a within-host loss of agr function. We report that events associated with agr inactivation result in agr -defective blood and nares strain pairs that are enriched in mutations compared to pairs from wild-type controls. The random distribution of mutations between colonizing and infecting strains from the same patient, and between strains from different patients, suggests that much of the genetic complexity of agr -defective strains results from prolonged infection or therapy-induced stress. However, in one of the agr -defective infecting strains, multiple genetic changes resulted in increased virulence in a murine model of bloodstream infection, bypassing the mutation of agr and raising the possibility that some changes were selected. Expression profiling correlated the elevated virulence of this agr -defective mutant to restored expression of the agr -regulated ESAT6-like type VII secretion system, a known virulence factor. Thus, additional mutations outside the agr locus can contribute to diversification and adaptation during infection by S. aureus agr mutants associated with poor patient outcomes., (Copyright © 2018 Altman et al.)
- Published
- 2018
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29. A High-fidelity Tactile Hand Simulator as a Training Tool to Develop Competency in Percutaneous Pinning in Residents.
- Author
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Wu YY, Rajaraman M, Guth J, Salopek T, Altman D, Sangimino M, and Shimada K
- Abstract
Introduction: We developed an economical three-dimensional printed and casted simulator of the hand for the training of percutaneous pinning. This simulator augments the traditional "See one, do one, teach one" training model., Methods: To evaluate the simulator, five expert orthopaedic surgeons were recruited to perform percutaneous pinning on the simulator and then to complete a questionnaire on its realism and expected usefulness. Evaluation was based on responses to multiple-choice questions and a Likert-type scale., Results: All subjects expressed that the tactile hand simulator is useful for residency training. They would recommend the simulator to their colleagues and indicated interest in testing future iterations. Subjects rated highly the realism of the material, the purchase of the pin, and the cortical-cancellous bone interface., Conclusion: The learning of tactile skills in addition to visual cues on a tactile simulator is expected to benefit residents. It provides a low-cost and low-risk environment outside the operating room for residents to hone their skills.
- Published
- 2018
- Full Text
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30. Corrigendum to "Community-Acquired Cavitary Pseudomonas Pneumonia Linked to Use of a Home Humidifier".
- Author
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Woods EC, Cohen GM, Bressman E, Lin D, Zeitouni NE, Beckford C, Hamula C, van Bakel H, Sullivan M, Altman DR, and Caplivski D
- Abstract
[This corrects the article DOI: 10.1155/2017/5474916.].
- Published
- 2018
- Full Text
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31. Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance in a Case of Persistent Enterococcus faecium Bacteremia.
- Author
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Chacko KI, Sullivan MJ, Beckford C, Altman DR, Ciferri B, Pak TR, Sebra R, Kasarskis A, Hamula CL, and van Bakel H
- Subjects
- Aged, Drug Resistance, Multiple, Bacterial genetics, Drug Therapy, Combination, Humans, Male, Microbial Sensitivity Tests, Vancomycin Resistance genetics, Bacteremia microbiology, Daptomycin pharmacology, Enterococcus faecium drug effects, Enterococcus faecium genetics, Linezolid pharmacology, Vancomycin pharmacology
- Abstract
Whole-genome sequencing was used to examine a persistent Enterococcus faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in fabF , encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug., (Copyright © 2018 Chacko et al.)
- Published
- 2018
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32. Community-Acquired Cavitary Pseudomonas Pneumonia Linked to Use of a Home Humidifier.
- Author
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Woods E, Cohen G, Bressman E, Lin D, Zeitouni NE, Beckford C, Hamula C, van Bakel H, Sullivan M, Altman DR, and Caplivski D
- Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that rarely causes pneumonia in otherwise healthy patients. We describe a case of community-acquired P. aeruginosa pneumonia in a previously healthy individual who likely acquired the infection from a home humidifier.
- Published
- 2017
- Full Text
- View/download PDF
33. Whole-genome sequencing identifies emergence of a quinolone resistance mutation in a case of Stenotrophomonas maltophilia bacteremia.
- Author
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Pak TR, Altman DR, Attie O, Sebra R, Hamula CL, Lewis M, Deikus G, Newman LC, Fang G, Hand J, Patel G, Wallach F, Schadt EE, Huprikar S, van Bakel H, Kasarskis A, and Bashir A
- Subjects
- DNA, Bacterial genetics, Drug Resistance, Multiple, Bacterial genetics, Microbial Sensitivity Tests, Mutation, Genome, Bacterial genetics, Gram-Negative Bacterial Infections microbiology, Quinolones pharmacology, Stenotrophomonas maltophilia immunology
- Abstract
Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S. maltophilia strains during clinical therapy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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34. Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.
- Author
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Rose HR, Holzman RS, Altman DR, Smyth DS, Wasserman GA, Kafer JM, Wible M, Mendes RE, Torres VJ, and Shopsin B
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents pharmacology, Cell Line, Cell Survival drug effects, Culture Media toxicity, Female, Humans, Male, Methicillin-Resistant Staphylococcus aureus isolation & purification, Methicillin-Resistant Staphylococcus aureus pathogenicity, Middle Aged, Neutrophils drug effects, Vancomycin pharmacology, Virulence, Young Adult, Bacterial Toxins toxicity, Cross Infection microbiology, Cross Infection mortality, Methicillin-Resistant Staphylococcus aureus growth & development, Pneumonia, Staphylococcal microbiology, Pneumonia, Staphylococcal mortality, Virulence Factors analysis
- Abstract
The current study identified bacterial factors that may improve management of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Isolates were obtained from 386 patients enrolled in a randomized, controlled study of antibiotic efficacy. Isolates were screened for production of virulence factors and for vancomycin susceptibility. After adjustment for host factors such as severity of illness and treatment modality, cytotoxic activity was strongly and inversely associated with mortality; however, it had no effect on clinical cure. Isolates having low cytotoxicity, which were derived largely from healthcare-associated clones, exhibited a greater prevalence of vancomycin heteroresistance, and they were recovered more often from patients who were older and frailer. Additionally, a clone with low cytotoxic activity was associated with death and poor clinical improvement. Clone specificity and attenuated virulence appear to be associated with outcome. To our knowledge, these are the first correlations between MRSA virulence and mortality in nosocomial pneumonia., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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- View/download PDF
35. Transmission of methicillin-resistant Staphylococcus aureus via deceased donor liver transplantation confirmed by whole genome sequencing.
- Author
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Altman DR, Sebra R, Hand J, Attie O, Deikus G, Carpini KW, Patel G, Rana M, Arvelakis A, Grewal P, Dutta J, Rose H, Shopsin B, Daefler S, Schadt E, Kasarskis A, van Bakel H, Bashir A, and Huprikar S
- Subjects
- Adult, Cadaver, DNA, Bacterial genetics, Female, Humans, Methicillin-Resistant Staphylococcus aureus genetics, Sequence Analysis, DNA, Staphylococcal Infections microbiology, Genome, Bacterial, Liver Transplantation adverse effects, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections transmission, Tissue Donors
- Abstract
Donor-derived bacterial infection is a recognized complication of solid organ transplantation (SOT). The present report describes the clinical details and successful outcome in a liver transplant recipient despite transmission of methicillin-resistant Staphylococcus aureus (MRSA) from a deceased donor with MRSA endocarditis and bacteremia. We further describe whole genome sequencing (WGS) and complete de novo assembly of the donor and recipient MRSA isolate genomes, which confirms that both isolates are genetically 100% identical. We propose that similar application of WGS techniques to future investigations of donor bacterial transmission would strengthen the definition of proven bacterial transmission in SOT, particularly in the presence of highly clonal bacteria such as MRSA. WGS will further improve our understanding of the epidemiology of bacterial transmission in SOT and the risk of adverse patient outcomes when it occurs., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2014
- Full Text
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36. Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus.
- Author
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Shopsin B, Eaton C, Wasserman GA, Mathema B, Adhikari RP, Agolory S, Altman DR, Holzman RS, Kreiswirth BN, and Novick RP
- Subjects
- Cross Infection epidemiology, Gene Frequency, Hospitals, Urban, Humans, Methicillin-Resistant Staphylococcus aureus pathogenicity, Microbial Sensitivity Tests, Mutation, New York City, Staphylococcal Infections epidemiology, Virulence genetics, Bacterial Proteins genetics, Cross Infection microbiology, Methicillin-Resistant Staphylococcus aureus genetics, Quorum Sensing genetics, Staphylococcal Infections microbiology, Trans-Activators genetics
- Abstract
Staphylococcus aureus organisms vary in the function of the staphylococcal virulence regulator gene agr. To test for a relationship between agr and transmission in S. aureus, we determined the prevalence and genetic basis of agr dysfunction among nosocomial methicillin-resistant S. aureus (MRSA) in an area of MRSA endemicity. Identical inactivating agr mutations were not detected in epidemiologically unlinked clones within or between hospitals. Additionally, most agr mutants had single mutations, indicating that they were short lived. Collectively, the results suggest that agr dysfunction is adaptive for survival in the infected host but that it may be counteradaptive outside infected host tissues.
- Published
- 2010
- Full Text
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37. Public perception of food allergy.
- Author
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Altman DR and Chiaramonte LT
- Abstract
Although studies that use the double-blind placebo-controled food challenge (DBPCFC) suggest that the prevalence of food allergy is about 2%, public belief in food allergy appears to be considerably higher. The study was undertaken to determine the magnitude and features of the American public's belief in food allergy by surveying a large, demographically balanced population. A simple question about food allergy was incorporated into a broad, self-reported, mailed consumer questionnaire. Demographically representative American households (5000) were surveyed by means of quota sample in 1989, 1992, and 1993. The response rate was 79, 75, and 74%, respectively. Of responding households, 16.2, 16.6, and 13.9%, respectively, of responding households reported an average of 1.17 household members with food allergy. Individuals reported to be allergic to foods were more likely to be female, particularly adult women. Male individuals with reported food allergy tended to be young, whereas no such skew was noted among female subjects. Geographic differences were observed in reported food allergy, with the highest rate in the Pacific region. Milk and chocolate were the individual foods most frequently implicated in food allergy. Trends were consistent over the time period studied. Perceived food allergy is widespread and persistent. The characteristics and demographic patterns of this belief are not reflective of known food allergy epidemiology derived from studies in which the DBPCFC is used.
- Published
- 1997
- Full Text
- View/download PDF
38. Public perception of food allergy.
- Author
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Altman DR and Chiaramonte LT
- Subjects
- Adolescent, Adult, Aged, Data Collection, Female, Humans, Male, Middle Aged, Perception, Surveys and Questionnaires, United States, Food Hypersensitivity diagnosis, Food Hypersensitivity epidemiology
- Abstract
Background: Although studies that use the double-blind placebo-controlled food challenge suggest that the prevalence of food allergy is about 2%, public belief in food allergy appears to be considerably higher., Objective: The study was undertaken to determine the magnitude and features of the American public's belief in food allergy by surveying a large, demographically balanced population., Methods: A simple question about food allergy was incorporated into a broad, self-reported, mailed consumer questionnaire. Five thousand demographically representative American households were surveyed by means of quota sample in 1989, 1992, and 1993., Results: The response rates were 79%, 75%, and 74%, respectively. Of responding households, 16.2%, 16.6%, and 13.9%, respectively, reported an average of 1.17 household members with food allergy. Individuals reported to be allergic to foods were more likely to be female, particularly adult women. Male individuals with reported food allergy tended to be young, whereas no such skew was noted among female subjects. Geographic differences were observed in reported food allergy, with the highest rate in the Pacific region. Milk and chocolate were the individual foods most frequently implicated in food allergy. Trends were consistent over the period studied., Conclusions: Perceived food allergy is widespread and persistent. The characteristics and demographic patterns of this belief are not reflective of known food allergy epidemiology derived from studies in which the double-blind placebo-controlled food challenge is used.
- Published
- 1996
- Full Text
- View/download PDF
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