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  • 1
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 9 ( 2023-09-21), p. e2334889-
    Abstract: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. Objective To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. Design, Setting, and Participants This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Interventions Near-infrared spectroscopy monitoring of Csat and Msat. Main Outcomes and Measures Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score & amp;lt;85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. Results A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower–hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher–hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO 2 ) in either group (0.2% vs −0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P  = .03). Conclusions and Relevance In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO 2 . Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia. Trial Registration ClinicalTrials.gov Identifier: NCT01702805
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 10 ( 2023-05-18), p. 8941-
    Abstract: Diversity of phage propagation, physical properties, and assembly promotes the use of phages in ecological studies and biomedicine. However, observed phage diversity is incomplete. Bacillus thuringiensis siphophage, 0105phi-7-2, first described here, significantly expands known phage diversity, as seen via in-plaque propagation, electron microscopy, whole genome sequencing/annotation, protein mass spectrometry, and native gel electrophoresis (AGE). Average plaque diameter vs. plaque-supporting agarose gel concentration plots reveal unusually steep conversion to large plaques as agarose concentration decreases below 0.2%. These large plaques sometimes have small satellites and are made larger by orthovanadate, an ATPase inhibitor. Phage head–host-cell binding is observed by electron microscopy. We hypothesize that this binding causes plaque size-increase via biofilm evolved, ATP stimulated ride-hitching on motile host cells by temporarily inactive phages. Phage 0105phi7-2 does not propagate in liquid culture. Genomic sequencing/annotation reveals history as temperate phage and distant similarity, in a virion-assembly gene cluster, to prototypical siphophage SPP1 of Bacillus subtilis. Phage 0105phi7-2 is distinct in (1) absence of head-assembly scaffolding via either separate protein or classically sized, head protein-embedded peptide, (2) producing partially condensed, head-expelled DNA, and (3) having a surface relatively poor in AGE-detected net negative charges, which is possibly correlated with observed low murine blood persistence.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2009
    In:  Archives of Psychiatric Nursing Vol. 23, No. 5 ( 2009-10), p. 366-375
    In: Archives of Psychiatric Nursing, Elsevier BV, Vol. 23, No. 5 ( 2009-10), p. 366-375
    Type of Medium: Online Resource
    ISSN: 0883-9417
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 2049085-9
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  • 4
    Online Resource
    Online Resource
    American Society for Microbiology ; 2015
    In:  EcoSal Plus Vol. 6, No. 2 ( 2015-10-23)
    In: EcoSal Plus, American Society for Microbiology, Vol. 6, No. 2 ( 2015-10-23)
    Abstract: DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils into DNA. Because of their essentiality in all cells and the fact that their reactions proceed via DNA breaks, topoisomerases have become important drug targets; the bacterial enzymes are key targets for antibacterial agents. This article discusses the structure and mechanism of topoisomerases and their roles in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors, including antibiotics in clinical use, is also discussed.
    Type of Medium: Online Resource
    ISSN: 2324-6200
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 159-159
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 159-159
    Abstract: Introduction: Previous research has shown that persons living with sickle cell disease (SCD) are at risk for frequent emergency department (ED) encounters, either with or without an associated inpatient stay. The disease manifests as acute onset vaso-occlusive crises or other severe and unpredictable complications that require immediate care. However, day hospital or other appropriate care settings to manage these health care events are not available to most of the population with SCD. Previous observations suggest that-while ED usage is high overall for this population-this usage is also episodic, with periods of high use interspersed with relatively low usage. We here seek to characterize both high-use and quiescent periods among patients seen in California non-federal hospitals over a 12-year period. Methods: The California Sickle Cell Data Collection project is a statewide effort to use a wide range of administrative, clinical, and other data sources to describe the population living with SCD, their health outcomes, and health care utilization patterns. The data here include 2005-2016 inpatient encounters and ED encounters (with or without an associated inpatient stay) linked by patient identifiers across data set and year. A validated case definition that suggests a high probability of a true SCD 'case' was applied: three or more occurrences of a SCD specific International Classification of Disease Code (version 9 or 10, depending on the year) within any 5 year period between 2005-2016. Only patients who met this case definition and had one year or more of follow-up time in the cohort were included in these analyses. We tabulated the numbers of encounters (inpatient and ED) for each patient for non-overlapping 4-week periods and used Poisson mixture models to evaluate whether encounter frequency could be characterized as a mixture of one or more discrete distributions. Based on these findings, we examined the timing and duration of periods of ED utilization for patients over the course of the study. Quiescent periods are defined as lengths of time in which a person has zero or near zero encounters in ED or inpatient settings. Occasional and high use periods of ED utilization are defined quantitatively by the model (as below). Results: There were 5,090 patients meeting the case definition with one year or more of time in follow up. Patients were followed for a median of 9.8 years (range 1.0 to 11.0). There were 94,196 ED encounters without and 59,064 ED encounters with an associated inpatient stay. A 3-component model best combined predictive power, parsimony, and clinical relevance (Figure 1, upper left), including quiescent periods (mean 0.09 encounters; 88.8% of 4-week periods); occasional-use periods (mean 1.28encounters; 10.8% of 4-week periods); and high-use periods (mean 7.48 encounters; 0.5% of 4-week periods). All but two of the subjects experienced at least one quiescent period during the study, 75.9% experienced at least one occasional-use period, and 8.0% experienced at least one high-use period. Spells of occasional- or high-use lasted a median of 8 weeks regardless of patient age, and 3.6% of these included at least some very high-use. Median lengths of quiescent periods were 24 weeks for patients aged less than 20 years, 16 weeks for those 20 years of age and older. Examples of distribution of utilization over time by certain patients are shown in Figure 1, upper right and both lower panels. Conclusions: The majority of patients with sickle cell disease experience discrete periods during which ED and inpatient hospital encounters are not uncommon, separated by somewhat longer periods with few-to-no encounters. The experiences of -8.0% of patients further include periods during which encounters were very frequent. Patients aged 20 years and older are more likely to experience these high frequency episodes. Further research is planned to identify whether particular health related events or patient characteristics are associated with these high-utilization spells. Figure 1 Figure 1. Disclosures Paulukonis: Bioverativ Inc.: Research Funding; Pfizer Inc.: Research Funding; Global Blood Therapeutics Inc.: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    American Astronomical Society ; 2018
    In:  The Astrophysical Journal Vol. 864, No. 2 ( 2018-09-10), p. 139-
    In: The Astrophysical Journal, American Astronomical Society, Vol. 864, No. 2 ( 2018-09-10), p. 139-
    Type of Medium: Online Resource
    ISSN: 1538-4357
    Language: Unknown
    Publisher: American Astronomical Society
    Publication Date: 2018
    detail.hit.zdb_id: 2207648-7
    detail.hit.zdb_id: 1473835-1
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  • 7
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 8
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 31 ( 2008-08-05), p. 10961-10966
    Abstract: CD4 + T cell responses to aerosol Mycobacterium tuberculosis (Mtb) infection are characterized by the relatively delayed appearance of effector T cells in the lungs. This delay in the adaptive response is likely critical in allowing the bacteria to establish persistent infection. Because of limitations associated with the detection of low frequencies of naïve T cells, it had not been possible to precisely determine when and where naïve antigen-specific T cells are first activated. We have addressed this problem by using early secreted antigenic target 6 (ESAT-6)-specific transgenic CD4 T cells to monitor early T cell activation in vivo . By using an adoptive transfer approach, we directly show that T cell priming to ESAT-6 occurs only after 10 days of infection, is initially restricted to the mediastinal lymph nodes, and does not involve other lymph nodes or the lungs. Primed CD4 T cells rapidly differentiated into proliferating effector cells and ultimately acquired the ability to produce IFN-γ and TNF-α ex vivo . Initiation of T cell priming was enhanced by two full days depending on the magnitude of the challenge inoculum, which suggests that antigen availability is a factor limiting the early CD4 T cell response. These data define a key period in the adaptive immune response to Mtb infection.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Rockefeller University Press ; 2010
    In:  Journal of Experimental Medicine Vol. 207, No. 6 ( 2010-06-07), p. 1153-1160
    In: Journal of Experimental Medicine, Rockefeller University Press, Vol. 207, No. 6 ( 2010-06-07), p. 1153-1160
    Abstract: After respiratory virus infections, memory CD8+ T cells are maintained in the lung airways by a process of continual recruitment. Previous studies have suggested that this process is controlled, at least in the initial weeks after virus clearance, by residual antigen in the lung-draining mediastinal lymph nodes (MLNs). We used mouse models of influenza and parainfluenza virus infection to show that intranasally (i.n.) primed memory CD8+ T cells possess a unique ability to be reactivated by residual antigen in the MLN compared with intraperitoneally (i.p.) primed CD8+ T cells, resulting in the preferential recruitment of i.n.-primed memory CD8+ T cells to the lung airways. Furthermore, we demonstrate that the inability of i.p.-primed memory CD8+ T cells to access residual antigen can be corrected by a subsequent i.n. virus infection. Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2010
    detail.hit.zdb_id: 1477240-1
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  • 10
    Online Resource
    Online Resource
    JSTOR ; 1980
    In:  Notes Vol. 36, No. 4 ( 1980-06), p. 899-
    In: Notes, JSTOR, Vol. 36, No. 4 ( 1980-06), p. 899-
    Type of Medium: Online Resource
    ISSN: 0027-4380
    RVK:
    Language: Unknown
    Publisher: JSTOR
    Publication Date: 1980
    detail.hit.zdb_id: 2231049-6
    detail.hit.zdb_id: 2066781-4
    SSG: 24,1
    SSG: 9,2
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