9 research outputs found

    The CD40-CD40L Dyad in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

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    The CD40-CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40-CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40-CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Both proteins are therefore attractive therapeutic candidates to modulate aberrant inflammatory responses in MS. Here, we discuss the genetic, experimental and clinical studies on the role of CD40 and CD40L interactions in EAE and MS and we explore novel approaches to therapeutically target this dyad to combat neuroinflammatory diseases

    Teaching Systematic Viewing to Final-Year Medical Students Improves Systematicity but Not Coverage or Detection of Radiologic Abnormalities

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    Purpose Systematic viewing of images is widely advocated in radiology; it is expected to lead to complete coverage of images and consequently more detection of abnormalities. Evidence on the efficacy of teaching systematic viewing to students is conflicting. The aim of this study was to investigate the effects of teaching systematic viewing to final-year medical students on systematicity of viewing behavior, coverage of the image, and detection. Methods Final-year medical students (n = 60) viewed 10 chest radiographs in a first series before training and another 10 radiographs in a second series after training. Between series, students were taught basic chest radiographic viewing, in either a systematic or a nonsystematic manner. With eye tracking, systematicity (Levenshtein distances), coverage (percentage of image viewed), and detection (sensitivity and specificity) were measured. Results In a mixed two-by-two design, significantly higher sensitivity was found after training compared with before training (F1,55 = 6.68, P = .012, ηp2 = .11) but no significant effect for type of training (F1,55 = 1.24, P = .30) and no significant interaction effect (F1,55 = 0.12, P = .73). Thus, training in systematic viewing was not superior to training in nonsystematic viewing. A significant interaction of training type and time of viewing was found on systematicity (F1,49 = 20.0, P <.01, ηp2 = .29) in favor of the systematic viewing group. No significant interaction was found for coverage (F1,49 = 0.43, P = .51) or specificity (F1,55 = .124, P = .73). Conclusions Both training types showed similar increases in sensitivity. Therefore, it might be advisable to pay less attention to systematic viewing and more attention to content, such as the radiologic appearances of diseases

    Teaching Systematic Viewing to Final-Year Medical Students Improves Systematicity but Not Coverage or Detection of Radiologic Abnormalities

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    Purpose Systematic viewing of images is widely advocated in radiology; it is expected to lead to complete coverage of images and consequently more detection of abnormalities. Evidence on the efficacy of teaching systematic viewing to students is conflicting. The aim of this study was to investigate the effects of teaching systematic viewing to final-year medical students on systematicity of viewing behavior, coverage of the image, and detection. Methods Final-year medical students (n = 60) viewed 10 chest radiographs in a first series before training and another 10 radiographs in a second series after training. Between series, students were taught basic chest radiographic viewing, in either a systematic or a nonsystematic manner. With eye tracking, systematicity (Levenshtein distances), coverage (percentage of image viewed), and detection (sensitivity and specificity) were measured. Results In a mixed two-by-two design, significantly higher sensitivity was found after training compared with before training (F1,55 = 6.68, P = .012, ηp2 = .11) but no significant effect for type of training (F1,55 = 1.24, P = .30) and no significant interaction effect (F1,55 = 0.12, P = .73). Thus, training in systematic viewing was not superior to training in nonsystematic viewing. A significant interaction of training type and time of viewing was found on systematicity (F1,49 = 20.0, P <.01, ηp2 = .29) in favor of the systematic viewing group. No significant interaction was found for coverage (F1,49 = 0.43, P = .51) or specificity (F1,55 = .124, P = .73). Conclusions Both training types showed similar increases in sensitivity. Therefore, it might be advisable to pay less attention to systematic viewing and more attention to content, such as the radiologic appearances of diseases

    The CD40–CD40L Dyad in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

    No full text
    The CD40–CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40–CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40–CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Both proteins are therefore attractive therapeutic candidates to modulate aberrant inflammatory responses in MS. Here, we discuss the genetic, experimental and clinical studies on the role of CD40 and CD40L interactions in EAE and MS and we explore novel approaches to therapeutically target this dyad to combat neuroinflammatory diseases

    Assessing the long-term health impact of Q-fever in the Netherlands: a prospective cohort study started in 2007 on the largest documented Q-fever outbreak to date

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    Contains fulltext : 109847.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Between 2007 and 2011, the Netherlands experienced the largest documented Q-fever outbreak to date with a total of 4108 notified acute Q-fever patients. Previous studies have indicated that Q-fever patients may suffer from long-lasting health effects, such as fatigue and reduced quality of life. Our study aims to determine the long-term health impact of Q-fever. It will also compare the health status of Q-fever patients with three reference groups: 1) healthy controls, 2) patients with Legionnaires' disease and 3) persons with a Q-fever infection but a-specific symptoms. METHODS/DESIGN: Two groups of Q-fever patients were included in a prospective cohort study. In the first group the onset of illness was in 2007-2008 and participation was at 12 and 48 months. In the second group the onset of illness was in 2010-2011 and participation was at 6 time intervals, from 3 to 24 months. The reference groups were included at only one time interval. The subjective health status, fatigue status and quality of life of patients will be assessed using two validated quality of life questionnaires. DISCUSSION: This study is the largest prospective cohort study to date that focuses on the effects of acute Q-fever. It will determine the long-term (up to 4 years) health impact of Q-fever on patients and compare this to three different reference groups so that we can present a comprehensive assessment of disease progression over time

    Predicting treatment response to vancomycin using bacterial DNA load as a pharmacodynamic marker in premature and very low birth weight neonates: A population PKPD study

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    Background: While positive blood cultures are the gold standard for late-onset sepsis (LOS) diagnosis in premature and very low birth weight (VLBW) newborns, these results can take days, and early markers of possible treatment efficacy are lacking. The objective of the present study was to investigate whether the response to vancomycin could be quantified using bacterial DNA loads (BDLs) determined by real-time quantitative polymerase chain reaction (RT-qPCR). Methods: VLBW and premature neonates with suspected LOS were included in a prospective observational study. Serial blood samples were collected to measure BDL and vancomycin concentrations. BDLs were measured with RT-qPCR, whereas vancomycin concentrations were measured by LC-MS/MS. Population pharmacokinetic–pharmacodynamic modeling was performed with NONMEM. Results: Twenty-eight patients with LOS treated with vancomycin were included. A one-compartment model with post-menstrual age (PMA) and weight as covariates was used to describe the time PK profile of vancomycin concentrations. In 16 of these patients, time profiles of BDL could be described with a pharmacodynamic turnover model. The relationship between vancomycin concentration and first-order BDL elimination was described with a linear-effect model. Slope S increased with increasing PMA. In 12 patients, no decrease in BDL over time was observed, which corresponded with clinical non-response. Discussion: BDLs determined through RT-qPCR were adequately described with the developed population PKPD model, and treatment response to vancomycin using BDL in LOS can be assessed as early as 8 h after treatment initiation

    Predicting treatment response to vancomycin using bacterial DNA load as a pharmacodynamic marker in premature and very low birth weight neonates: A population PKPD study

    No full text
    Background: While positive blood cultures are the gold standard for late-onset sepsis (LOS) diagnosis in premature and very low birth weight (VLBW) newborns, these results can take days, and early markers of possible treatment efficacy are lacking. The objective of the present study was to investigate whether the response to vancomycin could be quantified using bacterial DNA loads (BDLs) determined by real-time quantitative polymerase chain reaction (RT-qPCR). Methods: VLBW and premature neonates with suspected LOS were included in a prospective observational study. Serial blood samples were collected to measure BDL and vancomycin concentrations. BDLs were measured with RT-qPCR, whereas vancomycin concentrations were measured by LC-MS/MS. Population pharmacokinetic–pharmacodynamic modeling was performed with NONMEM. Results: Twenty-eight patients with LOS treated with vancomycin were included. A one-compartment model with post-menstrual age (PMA) and weight as covariates was used to describe the time PK profile of vancomycin concentrations. In 16 of these patients, time profiles of BDL could be described with a pharmacodynamic turnover model. The relationship between vancomycin concentration and first-order BDL elimination was described with a linear-effect model. Slope S increased with increasing PMA. In 12 patients, no decrease in BDL over time was observed, which corresponded with clinical non-response. Discussion: BDLs determined through RT-qPCR were adequately described with the developed population PKPD model, and treatment response to vancomycin using BDL in LOS can be assessed as early as 8 h after treatment initiation

    Clinical advantages and disadvantages of anabolic bone therapies targeting the WNT pathway

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    Diabetes mellitus: pathophysiological changes and therap

    Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles

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