TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Despite the potential benefits of total quality management (TQM), many healthcare organisations encountered difficulties in its implementation. The purpose of this paper is to explore the barriers to successful implementation of TQM in healthcare organisations of Iran.', 'This study involved a mixed research design. In-depth interviews were conducted with TQM practitioners to explore TQM implementation obstacles in Iranian healthcare organisations. In addition, this study involved survey-based research on the obstacles associated with successful TQM transformation.', "TQM implementation and its impact depend on the ability of managers to adopt and adapt its values and concepts in professional healthcare organisations. Unsuccessful TQM efforts in Iranian healthcare organisations can be attributed to the non-holistic approach adopted in its implementation, inadequate knowledge of managers' about TQM implementation, frequent top management turnover, poor planning, vague and short-termed improvement goals, lack of consistent managers' and employees' commitment to and involvement in TQM implementation, lack of a corporate quality culture, lack of team orientation, lack of continuous education and training and lack of customer focus. Human resource problems, cultural and strategic problems were the most important obstacles to TQM successful implementation, respectively.\Question: Does why TQM work in Iranian healthcare organisations?

SOLUTION: Understanding the factors that are likely to obstruct TQM implementation would enable managers to develop more viable strategies for achieving business excellence.

PROBLEM: Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\u2009<\u20090.05 and FC\u2009≥\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\u2009=\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.\Question: Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?

SOLUTION: For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.

PROBLEM: Context: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics.', 'Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR. Immunohistochemistry and flow cytometry assays were used to assess the expression of the protein phosphatase PP5 in endobronchial biopsies and ASM cells.', 'The production of CCL11 and CCL5 by TNF-α was insensitive to both fluticasone and dexamethasone in ASM cells from severe asthmatic compared to that in healthy subjects. Fluticasone-induced GRα nuclear translocation, phosphorylation at serine 211 and expression of GC-induced leucine zipper (GILZ) were significantly reduced in ASM cells from severe asthmatics compared to responses in healthy subjects. Levels of PP5 were increased in ASM cells from severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressive action on chemokine production and its ability to induce GRα nuclear translocation and GRE-dependent GILZ expression. In vivo PP5 expression was also increased in the ASM bundles in endobronchial biopsies in severe asthmatics.\Question: Does protein phosphatase 5 mediate corticosteroid insensitivity in airway smooth muscle in patients with severe asthma?

SOLUTION:
PP5-dependent impairment of GRα function represents a novel mechanism driving GC insensitivity in ASM in severe asthma.

