Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown ...benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC.
MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE
secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl
-induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model.
IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl
-induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB
), ucMSC(Starv + VitB
) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC.
The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.
Burnout in Belgian physicians and nurses Vandenbroeck, S; Van Gerven, E; De Witte, H ...
Occupational medicine (Oxford),
2017-Oct-01, 2017-10-01, Letnik:
67, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Burnout in healthcare is a worldwide problem. However, most studies focus narrowly on work-related factors and outcomes in one health profession or speciality.
To investigate the prevalence of ...burnout and its association with job demands, job resources, individual well-being, work-related attitudes and behaviour in physicians and nurses across different specialties.
Multi-centre cross-sectional study of physicians and nurses working in Belgian hospitals. An electronic questionnaire was used to assess job demands (e.g. workload), job resources (e.g. autonomy) and indicators of well-being, work-related attitudes and behaviours. Structural equation modelling was used to examine interrelationships between explanatory variables and outcomes.
1169 physicians and 4531 nurses participated; response rate 26%. High scores (>75th percentile in reference group of Dutch health care workers) were seen in 6% of the sample on three burnout dimensions (i.e. emotional exhaustion, depersonalization and personal competence) and in 13% for at least two dimensions. In contrast to the other dimensions, emotional exhaustion strongly related to almost all variables examined in the model. Positive associations were seen with workload, role conflicts, emotional burden and work-home interference and negative associations with learning and development opportunities and co-worker support. Emotional exhaustion correlated negatively with well-being, turnover intention, being prepared and able to work until retirement age, medication use, absenteeism and presenteeism.
Work-related factors were critical correlates of emotional exhaustion, which strongly related to poor health and turnover intention. Randomized controlled trials are suggested to underpin the effectiveness of interventions tackling job stressors and promoting job resources.
Mesenchymal stem or stromal cells (MSC) are under investigation as a potential immunotherapy. MSC are usually administered via intravenous infusion, after which they are trapped in the lungs and die ...and disappear within a day. The fate of MSC after their disappearance from the lungs is unknown and it is unclear how MSC realize their immunomodulatory effects in their short lifespan. We examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Tracking viable and dead human umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were present in the lungs immediately after infusion. Twenty‐four hours later, the majority of ucMSC were dead and found in the lungs and liver where they were contained in monocytic cells of predominantly non‐classical Ly6Clow phenotype. Monocytes containing ucMSC were also detected systemically. In vitro experiments confirmed that human CD14++/CD16‐ classical monocytes polarized toward a non‐classical CD14++CD16+CD206+ phenotype after phagocytosis of ucMSC and expressed programmed death ligand‐1 and IL‐10, while TNF‐α was reduced. ucMSC‐primed monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte reactions. These results demonstrate that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes, which subsequently modulate cells of the adaptive immune system. It can be concluded that monocytes play a crucial role in mediating, distributing, and transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602–615
Overview of the interaction of monocytic cells with infused mesenchymal stem or stromal cells (MSCs). Umbilical cord MSC (ucMSC) get entrapped in the lungs after intravenous infusion and are rapidly cleared from the system through phagocytosis by neutrophils, lung resident macrophages, and circulating monocytes. Monocytes containing ucMSC migrate via the blood stream to other sites, in particular to the liver. In addition, debris of ucMSC ends up in the liver where it is phagocytosed by liver‐resident Kupffer cells. Phagocytosis of ucMSC induces an immunomodulatory phenotype in monocytes and ucMSC‐primed monocytes induces Foxp3+CD25hiCD127‐CD4+ regulatory T cells.
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are ...characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions. Mature B cells were obtained from spleens by CD43
selection. B cells were co-cultured with MSC and stimulated with anti-IgM, anti-CD40, and IL-2; and after 7 days, B cell proliferation, phenotype, Immunoglobulin-G (IgG), and IL-10 production were analyzed. MSC did not inhibit B cell proliferation but increased the percentage of CD38
CD24
B cells (Bregs) and IL-10 production, while MSC-IFN-γ significantly reduced B cell proliferation and inhibited IgG production by B cells in a more potent fashion but did not induce Bregs or IL-10 production. Both MSC and MSC-IFN-γ required proximity to target cells and being metabolically active to exert their effects. Indoleamine 2,3 dioxygenase expression was highly induced in MSC-IFN-γ and was responsible of the anti-proliferative and Breg reduction since addition of tryptophan (TRP) restored MSC properties. Immunological conditions dictate the effect of MSC on B cell function. Under immunological quiescent conditions, MSC stimulate Breg induction; whereas, under inflammatory conditions, MSC inhibit B cell proliferation and maturation through depletion of TRP. This knowledge is useful for customizing MSC therapy for specific purposes by appropriate pretreatment of MSC.
Dealing with contaminants in Coulomb excitation of radioactive beams Morrison, L; Hadyńska-Klęk, K; Podolyák, Zs ...
27th International Nuclear Physics Conference, INPC 2019,Glasgow, United Kingdom,2019-07-29 - 2019-08-02,
12/2020, Letnik:
1643, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
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Data analysis of the Coulomb excitation experiment of the exotic 206Hg nucleus, recently performed at CERN's HIE-ISOLDE facility, needs to account for the contribution to target excitation due to the ...strongly-present beam contaminant 130Xe. In this paper, the contamination subtraction procedure is presented.
The aim of this study was to identify developmental patterns of job insecurity, taking into account quantitative as well as qualitative job insecurity, and to examine if these groups vary with regard ...to different work-related learning aspects, that is, occupational self-efficacy, learning from supervisor and colleagues, and acquired knowledge and skills (KSAOs). We conducted latent class growth analysis using three-wave data of 1366 Dutch employees. Five job insecurity patterns were identified: (1) high stable (n = 132), (2) moderate-low stable (n = 555), (3) low stable (n = 217), (4) decreasing (n = 357) and (5) increasing (n = 105). In every class, the change pattern was similar for quantitative and qualitative job insecurity. Those in trajectories with high initial levels of job insecurity had lower initial levels of occupational self-efficacy, learning from others, and KSAOs than those with low initial levels of job insecurity. Additionally, job insecurity trajectories differed in the development of occupational self-efficacy over time. The findings indicate that there are distinct trajectories of the combination of quantitative and qualitative job insecurity, and that these demonstrate a substantial amount of heterogeneity concerning work-related learning.
The directed transfer function (DTF) and the partial directed coherence (PDC) are frequency-domain estimators that are able to describe interactions between cortical areas in terms of the concept of ...Granger causality. However, the classical estimation of these methods is based on the multivariate autoregressive modelling (MVAR) of time series, which requires the stationarity of the signals. In this way, transient pathways of information transfer remains hidden. The objective of this study is to test a time-varying multivariate method for the estimation of rapidly changing connectivity relationships between cortical areas of the human brain, based on DTF/PDC and on the use of adaptive MVAR modelling (AMVAR) and to apply it to a set of real high resolution EEG data. This approach will allow the observation of rapidly changing influences between the cortical areas during the execution of a task. The simulation results indicated that time-varying DTF and PDC are able to estimate correctly the imposed connectivity patterns under reasonable operative conditions of signal-to-noise ratio (SNR) ad number of trials. An SNR of Ave and a number of trials of at least 20 provide a good accuracy in the estimation. After testing the method by the simulation study, we provide an application to the cortical estimations obtained from high resolution EEG data recorded from a group of healthy subject during a combined foot-lips movement and present the time-varying connectivity patterns resulting from the application of both DTF and PDC. Two different cortical networks were detected with the proposed methods, one constant across the task and the other evolving during the preparation of the joint movement.
We investigated decays of K 51 , 52 , 53 at the ISOLDE Decay Station at CERN in order to understand the mechanism of the β -delayed neutron-emission ( β n ) process. The experiment quantified neutron ...and γ -ray emission paths for each precursor. We used this information to test the hypothesis, first formulated by Bohr in 1939, that neutrons in the β n process originate from the structureless “compound nucleus.” The data are consistent with this postulate for most of the observed decay paths. The agreement, however, is surprising because the compound-nucleus stage should not be achieved in the studied β decay due to insufficient excitation energy and level densities in the neutron emitter. In the K 53 β n decay, we found a preferential population of the first excited state in Ca 52 that contradicted Bohr’s hypothesis. The latter was interpreted as evidence for direct neutron emission sensitive to the structure of the neutron-unbound state. We propose that the observed nonstatistical neutron emission proceeds through the coupling with nearby doorway states that have large neutron-emission probabilities. The appearance of “compound-nucleus” decay is caused by the aggregated small contributions of multiple doorway states at higher excitation energy. Published by the American Physical Society 2024
This paper addresses the construct and predictive validity of two methods for classifying respondents as victims of workplace bullying. Although bullying is conceived as a complex phenomenon, the ...dominant method used in bullying surveys, the operational classification method, only distinguishes two groups: victims versus non-victims. Hence, the complex nature of workplace bullying may not be accounted for. Therefore a latent class cluster approach is suggested to model the data, which was obtained by using the Negative Acts Questionnaire (NAQ) administered to employees in Belgium (n=6,175). Latent class modelling is a method of analysis that does not appear to have been used in occupational health psychology before. In this study, six latent classes emerged: "not bullied," "limited work criticism," "limited negative encounters," "sometimes bullied," "work related bullied," and "victims." The results show that compared to the traditional operational classification method, the latent class cluster approach shows higher construct and higher predictive validity with respect to self-assessments and indicators of strain and well-being at work. The consequences of these results for theory, future research, and practice are discussed.
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