Necroptosis is a form of programmed cell death that depends on the activation of receptor interacting protein kinase-1 (RIPK1) and RIPK3 by receptors such as tumor necrosis factor (TNF) receptor-1. ...Structural studies indicate that activation of RIPK3 by RIPK1 involves the formation of oligomers via interactions of the RIP homotypic interaction motif (RHIM) domains shared by both proteins; however, the molecular mechanisms by which this occurs are not fully understood. To gain insight into this process, we constructed versions of RIPK3 that could be induced to dimerize or oligomerize in response to a synthetic drug. Using this system, we find that although the formation of RIPK3 dimers is itself insufficient to trigger cell death, this dimerization seeds a RHIM-dependent complex, the propagation and stability of which is controlled by caspase-8 and RIPK1. Consistent with this idea, we find that chemically enforced oligomerization of RIPK3 is sufficient to induce necroptosis, independent of the presence of the RHIM domain, TNF stimulation or RIPK1 activity. Further, although RIPK1 contributes to TNF-mediated RIPK3 activation, we find that RIPK1 intrinsically suppresses spontaneous RIPK3 activation in the cytosol by controlling RIPK3 oligomerization. Cells lacking RIPK1 undergo increased spontaneous RIPK3-dependent death on accumulation of the RIPK3 protein, while cells containing a chemically inhibited or catalytically inactive form of RIPK1 are protected from this form of death. Together, these data indicate that RIPK1 can activate RIPK3 in response to receptor signaling, but also acts as a negative regulator of spontaneous RIPK3 activation in the cytosol.
Background: Counterproductive behavior costs organizations and their members which will ultimately affect work-related outcomes and organizational success. Organizational justice has the potential to ...affect the level of counter productive behavior. However, there is a paucity of studies to show the link between counterproductive behavior and organizational justice dimensions in the Ethiopian health care system context. Therefore, the purpose of this research was to look into the link between organizational justice, and counterproductive work behavior among health care professionals. Methods: The 395 study participants were chosen using a facility-based cross-sectional study methodology. A proportionate stratified systematic random sampling technique was deployed to select study participants from health facilities. Data was gathered using a structured self-report questionnaire by CWB Scale that was developed by Spector and Fox (2005) with Cronbach's alpha of an average of (0.84-0.87). Data was obtained, cleaned, and entered by Epidata3.1. Finally, for descriptive and inferential statistical analysis, the data was exported to SPSS version 23.0. Results: According to the findings, 159 (40.3%) of the study participants engaged in counterproductive job activities. Organizational justice was assumed to be fair by about half of the respondents, 202 (52.2%). Distributive Justice (=-0.141, p.05) was found to be a significant and negative predictor of counterproductive work behavior in the regression analysis. Age (beta=-0.014, p< 0.05), the average number of hours worked every week (beta=-0.009, p< 0.05), and experience (beta=0.016, p< 0.05) were found to be significant predictors of the counterproductive work behaviors. Conclusion and Recommendation: This study indicated that distributive justice show significant contribution in reduction of counterproductive work behaviour.As a result, improving organizational justice can aid to reduce counterproductive work behavior which in turn increases the facility's productivity. Keywords: counterproductive, work behavior, organizational justice, health care professional, Ethiopia
Abstract
Background
Hospitals across Australia are implementing Clinical Information Systems, e.g. Electronic Medication Management Systems (EMMS) at a rapid pace to moderate health services. The ...benefits of the EMMS depend on the acceptance of the system by the clinicians. The study hospital used a unique patient-centric implementation strategy that was based on the guiding principle of “one patient, one chart” to avoid a patient being on a hybrid medication chart. This paper aims to study the factors facilitating or hindering the adoption of the EMMS as viewed by clinicians and the implementation team.
Methods
Four focus groups (FG), one each for (1) doctors, (2) nurses, (3) pharmacists, and (4) implementation team, were conducted. A guide for the FG was based on the Unified Theory of Acceptance and Use of Technology (UTAUT).
Results
A total of 23 unique subthemes were identified and were grouped into five main themes (1) implementation strategy, (2) organisational outcome of EMMS, (3) individual impact of EMMS, (4) IT product, and (5) organisational culture. Clinicians reported improvement in their workflow efficiency post-EMMS implementation. They also reported some challenges in using the EMMS that centered around the area of infrastructure, technical and design issues. Additionally, the implementation team highlighted two crucial factors influencing the success of EMMS implementation, namely: (1) the patient-centric implementation strategy, and (2) the organisation readiness.
Conclusion
Overall, this study outlines the implementation process of the EMMS in a large healthcare facility from the clinicians’ and the implementation team’s perspectives using UTAUT model. The result suggests that clinicians’ acceptance of the EMMS was highly influenced by the unique implementation strategy (namely, patient-centric approach and clinical leadership in the implementation team). Whereas the level of adoption of EMMS by clinicians was determined by their level of perceived and realised benefits. On the other hand, a number of barriers to the adoption of EMMS were discovered, namely, general training instead of customised training based on local needs, technical and design issues and lack of availability of computer systems. It is suggested that promptly resolving these issues can improve the adoption of the EMMS.
This study attempts to understand the factors that influence clinician resistance to the implementation of health information technology in a mandatory setting.
A survey study was conducted with 202 ...clinicians regarding their perceptions of the implementation of electronic medication management systems (eMMS) in an Australian hospital. The data was collected during the initial roll-out of eMMS for model validation and quantitative analysis.
The overall results indicated that performance expectancy, switching costs, and facilitating conditions are direct predictors of clinician resistance, whereas effort expectancy and social influence showed indirect effects on clinician resistance through performance expectancy or switching costs.
The study is among the first study that investigates passive clinician resistance to the implementation of health information technology in a health organisation. This study also focused on opposition behaviour among under-examined degrees of resistance.
This study provides some insights to the hospital management on how to mitigate clinician resistance in the implementation of health information technology.
Other types of clinician resistance, such as postponement and rejection, are not examined in this study. Future research on postponement behaviour and rejection behaviour is needed to have a more comprehensive view of clinician resistance.
Many IS studies focus on initial user perceptions as drivers of initial IS success, but these perceptions may change over time. This study aims to examine whether there is any difference in the ...drivers of IS success between the initial adoption and the initial assimilation stages. With the Expectation Confirmation Model as the theoretical lens, a repeated cross-sectional study was conducted regarding clinicians’ perceptions of the implementation of electronic medication management systems (eMMS) in an Australian hospital, one at the time of implementation and another one at one year after the implementation. The results indicated that the means of perceived usefulness, perceived ease of use, social influence, clinician satisfaction, and organizational benefits are significantly higher in the initial assimilation stage than in the initial adoption stage, which means that expectations have been positively confirmed in the initial assimilation stage. More importantly, while perceived usefulness and social influence remain important one year after the implementation, perceived ease of use and facilitating conditions are moving toward a decrease in importance to the success of eMMS. This study provides a better understanding of how the importance of the factors influencing eMMS success changes over time.
Response Sahasrabuddhe, V. V.; Gunja, M. Z.; Graubard, B. I. ...
JNCI : Journal of the National Cancer Institute,
05/2013, Volume:
105, Issue:
9
Journal Article
In the present study, we have employed a unique breast cancer cell line (Met-1, which was derived from a high metastatic potential tumor in transgenic mice expressing polyomavirus middle T oncogene) ...to study the role of CD44 variant isoform(s) in the regulation of metastatic breast tumor cell behavior. The results of reverse transcriptase-polymerase chain reaction, Southern blot, nucleotide sequencing, immunoprecipitation, and immunoblot analyses indicated that these cells express a major CD44 isoform (molecular weight approximately 260 kDa) containing a v3,8-10 exon insertion (designated as CD44v3,8-10). In addition, we have determined that CD44v3,8-10 binds specifically to the cytoskeletal proteins such as ankyrin. Biochemical analyses, using competition binding assays and a synthetic peptide identical to NGGNGTVEDRKPSEL (a sequence located between aa480 and aa494 of CD44v3,8-10) indicate that this 15-amino acid peptide binds specifically to the cytoskeletal protein ankyrin (but not to fodrin or spectrin). This peptide competes effectively for ankyrin binding to CD44v3,8-10. Therefore, we believe that the sequence 480NGGNGTVEDRKPSE494L, located at the cytoplasmic domain of CD44v3,8-10, is required for the ankyrin binding. We have also detected that CD44v3,8-10-containing Met-1 cells are capable of forming membrane spikes or "invadopodia" structures and undergo active migration processes. Treatments of Met-1 cells with certain agents including anti-CD44v3 antibody, cytochalasin D (a microfilament inhibitor), and W-7 (a calmodulin antagonist), but not colchicine (a microtubule disrupting agent) effectively inhibit "invadopodia" formation and subsequent tumor cell migration. Further analyses using zymography assays and double immunofluorescence staining indicated that CD44v3,8-10 is closely associated with the active form of matrix metalloproteinase, MMP-9, in a complex within "invadopodia" structures. These findings suggest that CD44v3,8-10 plays an important role in linking ankyrin to the membrane-associated actomyosin contractile system required for "invadopodia" formation (coupled with matrix degradation activities) and tumor cell migration during breast cancer progression.
Severe ischemic injury or infarction of myocardium may cause activation of matrix metalloproteinases (MMPs) and damage the interstitial matrix. However, it is unknown whether MMP activation and ...matrix damage occur after moderate ischemia and reperfusion that result in myocardial stunning without infarction, and if so whether such changes contribute to postischemic myocardial expansion and contractile dysfunction. To address these questions, open-chest anesthetized pigs underwent 90 min of regional ischemia (subendocardial blood flow 0.4 +/- 0.1 ml. g(-1). min(-1)) and 90 min of reperfusion. After ischemia plus reperfusion, histological and ultrastructural examination revealed no myocardial infarction or inflammatory cell infiltration. Myocardial MMP-9 content increased threefold with a fourfold increase in the active form (P < 0.001). Myocardial collagenase content doubled (P < 0.01) but remained in latent form. MMP-2 and tissue inhibitors of metalloproteinases were unaffected. Despite increases in MMPs, collagen ultrastructure (assessed by cell maceration scanning electron microscopy) was unaltered. Intracoronary administration of the MMP inhibitor GM-2487 did not prevent or attenuate myocardial expansion (assessed by regional diastolic dimensions at near-zero left ventricular pressure) or contractile dysfunction. We conclude that although moderate ischemia and reperfusion alter myocardial MMP content and activity, these effects do not result in damage to interstitial collagen, nor do they contribute to myocardial expansion or contractile dysfunction.
La utilización de los estudios de montaña requiere de narrativas integradoras para la geoalfabetización sobre paisajes socioecológicos productivos y motiva más investigaciones transdisciplinares en ...el campo de la montología. Concebimos este artículo como la confluencia de la experiencia individual y el razonamiento colectivo hacia la formación de grupos de investigación sinérgicos que se ocupan de la ciencia de montaña convergente, para hacer avanzar la montología a un nuevo nivel, mediante el cual el pensamiento innovador sobre la ciencia de la sustentabilidad y el desarrollo regenerativo incorpora propuestas alternativas para el mantenimiento, la mejora, o regeneración de las condiciones de vida de los paisajes de montaña. Buscamos utilizar este marco contemporáneo de sustentabilidad y restauración ecológica como el ímpetu para comprender mejor las relaciones de la naturaleza y la cultura, desde una perspectiva transdisciplinar, en montañas habitadas que operan en cuatro dimensiones (largo, ancho, alto y tiempo). El artículo está orientado a potenciar la transversalidad de temáticas en torno a las montañas como sistemas socioecológicos productivos, en una nueva disciplina académica institucionalizada y convergente. Concluimos con un llamado a un desarrollo regenerativo, sustentable y consiliente en las montañas del mundo.
The balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) determines the extent of connective tissue degradation and remodeling.
To determine ...whether pterygium, characterized by fibrovascular invasion into the cornea, may in part be mediated by an increased activity of MMPs.
Expression of transcripts and proteins of MMPs, TIMPs, and urokinase plasminogen activator (uPA) by cultured human pterygium head, body, and subconjunctival fibroblasts, and normal corneal and conjunctival fibroblasts were determined by Northern hybridization, enzyme-linked immunosorbent assay, Western blotting, zymography, and quantitative collagenase assay, respectively.
Compared with normal conjunctival fibroblasts from 6 subjects, the expression of MMP-1 and MMP-3 transcripts was dramatically increased in pterygium head fibroblasts of 8 patients, but not in pterygium body fibroblasts of 6 patients. The protein levels and collagenolytic and caseinolytic activities of MMP-1 and/or MMP-3 were also markedly increased in pterygium head fibroblasts. The MMP-1 and MMP-3 proteins and activity decreased in order from pterygium head to body to subconjunctival fibroblasts. There was no difference in the transcript and protein expression of MMP-2, TIMP-1, TIMP-2, and uPA among these groups.
Pterygium head fibroblasts express increased mRNA, protein, and activities of MMP-1 and MMP-3.
Overexpression of MMP-1 and MMP-3, a phenotype previously linked with UV exposure in dermal fibroblasts to explain the pathologic finding of elastotic degeneration, suggests that pterygium head fibroblasts might be intrinsically altered by UV, which might be responsible for corneal invasion.
PDF
