112,460 research outputs found

    The effect of pathophysiology on pharmacokinetics in the critically ill patient - Concepts appraised by the example of antimicrobial agents

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    Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward

    A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

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    The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

    A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

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    Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    F-00249-2021R1 supplementary _figures_1_9

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    F-00249-2021R1 Supplementary _figures_1_9 showing original western blot data</p

    USPHS Psychologist F. M. Wickersham Utilizes the Ink Blot Test

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    At the USPHS Hospital, the psychologist, F. M. Wickersham, Ph.D., used many tests to determine personality characteristics and aptitudes, including the Rorshach or ink blot test which gauges a person\u27s capacity for abstract thinking and high-level organization. Published in the Fort Worth Star-Telegram morning edition, January 23, 1950.https://mavmatrix.uta.edu/specialcollections_startelegram1950s/1521/thumbnail.jp

    SDS-PAGE and Western blot analysis purified RSV F.

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    <p>Sf9 insect cells were infected at MOI = 1 with BV683 expressing modified full length RSV F and harvested 67 hr post infection and purified as described in the Methods. Purified RSV F protein was analyzed for purity by SDS-PAGE under non-reducing or reducing conditions to retain or disrupt intra-protein disulfide bond between F1 and F2 subunit. (A) Coomassie blue strained gel of replicate samples of non-reduced or reduced purified RSV F. (B) Western blot using anti-RSV F1 monoclonal antibody of non-reduced and reduced RSV F. The location of non-reduced polypeptide (F), reduced but full length (F0), and F1 and F2 polypeptides are indicated with protein marker molecular weight x 10<sup>3</sup> included in the first lane.</p

    Dot blot and Western blot assays.

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    Seven different strains of Aa-bacteria (Aa-A, Aa-B, Aa-C, Aa-D, Aa-E, Aa-F, Aa-X), Pg, Tf and E.coli bacteria are presented before (week 0) and after (week 15) immunization, together with MAA-BSA, BSA, and Aa-HSP60. Dot blot results are presented in Fig 5A. Western blot results are presented in Figs 5B and 5C. Samples were separated by SDS-PAGE and blotted by Western Blotting. Molecular weight marker in kilodaltons (kDa) is shown on the left. Fragments of the same original image were spliced together to re-order lanes to remove irrelevant lanes.</p

    [Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]

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    Newspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
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