904 research outputs found

    Predicting employees' commitment to and support for organisational change

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    This study aimed to identify factors that predict employees' commitment to and support for organisational change. The three components of Herscovitch and Meyer's (2002) commitment to organisational change model were hypothesised to mediate the relationship between organisational climate and behavioural support for organisational change. Data were collected from a Queensland government department (N = 342). Analysis of correlations revealed that organisational climate, commitment to change, and behavioural support for change variables were all significantly related. Structural equation modelling demonstrated that affective, normative, and continuance commitment to change were all predictors of behavioural support for organisational change. Positive work climate also contributed directly to the prediction of behavioural support for change over and above the indirect influence through commitment to organisational change, indicating a partial mediation effect. These findings support Herscovitch and Meyer's (2002) three-component model of commitment to organisational change and extend their nomological network by showing the relevance of two types of organisational climate to the core components of the model. Affective commitment to organisational change is a positive influence on employees' behavioural support for change and also reflects healthy aspects of the organisational climate. However, continuance commitment to organisational change is detrimental influence on employees' behavioural support for change and is linked with unhealthy dimensions of the organisational climate

    The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1

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    Following the current hypothesis that acute schizophrenic psychotic illness is associated with a triatal ‘hyperdopaminergic state’, presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photonemission- tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECTligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia

    The Transcription Factor NURR1 Exerts Concentration-Dependent Effects on Target Genes Mediating Distinct Biological Processes

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    The transcription factor NURR1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype in midbrain dopamine neurons. Conversely, decreased NURR1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson’s disease and drug addiction. In order to better understand the nature of NURR1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a human neural cellular background (SK-N-AS cells) in which to generate a number of stable clonal lines with graded NURR1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these NURR1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of NURR1-responsive genes and demonstrated the potential importance of concentration-dependent NURR1 effects in the differential regulation of distinct NURR1 target genes and biological pathways. These data support the promise of NURR1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons

    Intermediate filament–membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength

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    By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF–membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF–membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97166/1/jfo12080.pd

    Comparison of a nurse initiated insulin infusion protocol for intensive insulin therapy between adult surgical trauma, medical and coronary care intensive care patients

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    <p>Abstract</p> <p>Background</p> <p>Sustained hyperglycemia is a known risk factor for adverse outcomes in critically ill patients. The specific aim was to determine if a nurse initiated insulin infusion protocol (IIP) was effective in maintaining blood glucose values (BG) within a target goal of 100–150 mg/dL across different intensive care units (ICUs) and to describe glycemic control during the 48 hours after protocol discontinuation.</p> <p>Methods</p> <p>A descriptive, retrospective review of 366 patients having 28,192 blood glucose values in three intensive care units, Surgical Trauma Intensive Care Unit (STICU), Medical (MICU) and Coronary Care Unit (CCU) in a quaternary care hospital was conducted. Patients were > 15 years of age, admitted to STICU (n = 162), MICU (n = 110) or CCU (n = 94) over 8 months; October 2003-June 2004 and who had an initial blood glucose level > 150 mg/dL. We summarized the effectiveness and safety of a nurse initiated IIP, and compared these endpoints among STICU, MICU and CCU patients.</p> <p>Results</p> <p>The median blood glucose values (mg/dL) at initiation of insulin infusion protocol were lower in STICU (188; IQR, 162–217) than in MICU, (201; IQR, 170–268) and CCU (227; IQR, 178–313); <it>p </it>< 0.0001. Mean time to achieving a target glucose level (100–150 mg/dL) was similar between the three units: 4.6 hours in STICU, 4.7 hours in MICU and 4.9 hours in CCU (<it>p </it>= 0.27). Hypoglycemia (BG < 60 mg/dL) occurred in 7% of STICU, 5% of MICU, and 5% of CCU patients (<it>p </it>= 0.85). Protocol violations were uncommon in all three ICUs. Mean blood glucose 48 hours following IIP discontinuation was significantly different for each population: 142 mg/dL in STICU, 167 mg/dL in MICU, and 160 mg/dL in CCU (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>The safety and effectiveness of nurse initiated IIP was similar across different ICUs in our hospital. Marked variability in glucose control after the protocol discontinuation suggests the need for further research regarding glucose control in patients transitioning out of the ICU.</p

    Translational Model for External Volume Expansion in Irradiated Skin

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    Introduction: External Volume Expansion (EVE) treatment has gained popularity in breast reconstruction, enriching recipient sites for fat grafting. For patients receiving radiotherapy (XRT), results of EVE use vary, partly because the effects of EVE on irradiated tissue are not well understood. Based on our previous work with EVE and XRT, we developed a new translational model to investigate the effects of EVE in the setting of chronic radiation skin injury. Methods: Twenty-Eight SKH1-E mice received 50Gy of beta-radiation to each flank. Animals were monitored until chronic radiation fibrosis developed (8 weeks). EVE was then applied to one side for 6hrs on 5 consecutive days. The opposite side served as control. Hyperspectral Imaging (HSI) was used to assess perfusion changes before and after EVE. Mice were sacrificed at 5 days (n=14) and 15 days (n=14) after last application for histological analysis. Tissue samples were stained for vascularity (CD31) and collagen composition (Picro-Sirius red). Results: All animals developed skin fibrosis 8 weeks post-radiation, and changes in perfusion verified skin damage. EVE application induced edema on treated sides. Five days post-application, both sides were hypo-perfused as seen by HSI; with the EVE side 13% more ischemic than the untreated side (p\u3c0.001). Perfusion returned to control side levels by day 15. Blood vessels increased 20% by day 5 in EVE versus control. Collagen composition showed no difference in scar index analysis. Conclusion: EVE temporarily augments radiation-induced hypo-perfusion, likely due to transient edema. Fibrosis remained unchanged after EVE, possibly accounting for the limited expansion seen in patients. It appears that EVE induces angiogenic effect but does not affect dermal collagen composition. Future efforts should focus on reducing fibrosis post radiation to allow EVE to achieve its full potential, to benefit irradiated patients
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