Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, >= 1 major criteria), 'probable' (n = 10, >= 2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (> 12 arbitrary units) and the lactate-to-creatine ratio (L/Cr > 0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. MRS-detected brain tissue lactate levels can be quantified. MRS lactate and lactate/Cr are increased in children with mitochondrial disease. CSF lactate is less suitable as marker of mitochondrial disease

The ConCom Safety Management Scale:Developing and testing a measurement instrument for control-based and commitment-based safety management approaches in hospitals

Background Nursing management is considered important for patient safety. Prior research has predominantly focused on charismatic leadership styles, although it is questionable whether these best characterise the role of nurse managers. Managerial control is also relevant. Therefore, we aimed to develop and test a measurement instrument for control-based and commitment-based safety management of nurse managers in clinical hospital departments. Methods A cross-sectional survey design was used to test the newly developed questionnaire in a sample of 2378 nurses working in clinical departments. The nurses were asked about their perceptions of the leadership behaviour and management practices of their direct supervisors. Psychometric properties were evaluated using confirmatory factor analysis and reliability estimates. Results The final 33-item questionnaire showed acceptable goodness-of-fit indices and internal consistency (Cronbach’s α of the subscales range: 0.59–0.90). The factor structure revealed three subdimensions for control-based safety management: (1) stressing the importance of safety rules and regulations; (2) monitoring compliance; and (3) providing employees with feedback. Commitment-based management consisted of four subdimensions: (1) showing role modelling behaviour; (2) creating safety awareness; (3) showing safety commitment; and (4) encouraging participation. Construct validity of the scale was supported by high factor loadings and provided preliminary evidence that control-based and commitment-based safety management are two distinct yet related constructs. The findings were reconfirmed in a cross-validation procedure. Conclusion The results provide initial support for the construct validity and reliability of our ConCom Safety Management Scale. Both management approaches were found to be relevant for managing patient safety in clinical hospital departments. The scale can be used to deepen our understanding of the influence of patient safety management on healthcare professionals’ safety behaviour as well as patient safety outcomes

Elderly patients' decision-making embedded in the social context

BACKGROUND: Older patients are increasingly encouraged to be actively involved but how they perceive their role in the decision-making process varies according to their health care providers and their health situation. Their role could be influenced by their social context but more specifically by subjective norms (i.e. patients' view of the role that significant others expect them to play in the decision-making process) and perceived soc

Disparate Effects of p24α and p24δ on Secretory Protein Transport and Processing

Contains fulltext : 34883.pdf ( ) (Open Access)BACKGROUND: The p24 family is thought to be somehow involved in endoplasmic reticulum (ER)-to-Golgi protein transport. A subset of the p24 proteins (p24alpha(3), -beta(1), -gamma(3) and -delta(2)) is upregulated when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated to produce vast amounts of their major secretory cargo, the prohormone proopiomelanocortin (POMC). METHODOLOGY/PRINCIPAL FINDINGS: Here we find that transgene expression of p24alpha(3 )or p24delta(2) specifically in the Xenopus melanotrope cells in both cases causes an effective displacement of the endogenous p24 proteins, resulting in severely distorted p24 systems and disparate melanotrope cell phenotypes. Transgene expression of p24alpha(3) greatly reduces POMC transport and leads to accumulation of the prohormone in large, ER-localized electron-dense structures, whereas p24delta(2)-transgenesis does not influence the overall ultrastructure of the cells nor POMC transport and cleavage, but affects the Golgi-based processes of POMC glycomaturation and sulfation. CONCLUSIONS/SIGNIFICANCE: Transgenic expression of two distinct p24 family members has disparate effects on secretory pathway functioning, illustrating the specificity and non-redundancy of our transgenic approach. We conclude that members of the p24 family furnish subcompartments of the secretory pathway with specific sets of machinery cargo to provide the proper microenvironments for efficient and correct secretory protein transport and processing

A framework and a measurement instrument for sustainability of work practices in long-term care

<p>Abstract</p> <p>Background</p> <p>In health care, many organizations are working on quality improvement and/or innovation of their care practices. Although the effectiveness of improvement processes has been studied extensively, little attention has been given to sustainability of the changed work practices after implementation. The objective of this study is to develop a theoretical framework and measurement instrument for sustainability. To this end sustainability is conceptualized with two dimensions: routinization and institutionalization.</p> <p>Methods</p> <p>The exploratory methodological design consisted of three phases: a) framework development; b) instrument development; and c) field testing in former improvement teams in a quality improvement program for health care (N _teams= 63, N _individual= 112). Data were collected not until at least one year had passed after implementation.</p> <p>Underlying constructs and their interrelations were explored using Structural Equation Modeling and Principal Component Analyses. Internal consistency was computed with Cronbach's alpha coefficient. A long and a short version of the instrument are proposed.</p> <p>Results</p> <p>The χ²- difference test of the -2 Log Likelihood estimates demonstrated that the hierarchical two factor model with routinization and institutionalization as separate constructs showed a better fit than the one factor model (p < .01). Secondly, construct validity of the instrument was strong as indicated by the high factor loadings of the items. Finally, the internal consistency of the subscales was good.</p> <p>Conclusions</p> <p>The theoretical framework offers a valuable starting point for the analysis of sustainability on the level of actual changed work practices. Even though the two dimensions routinization and institutionalization are related, they are clearly distinguishable and each has distinct value in the discussion of sustainability. Finally, the subscales conformed to psychometric properties defined in literature. The instrument can be used in the evaluation of improvement projects.</p

Perspective Chapter: A Renewed Perspective on Lean Six Sigma in Healthcare – People and Performance

The Lean Six Sigma (LSS) approach has taken a central role in healthcare quality management, and many studies report positive effects of the method on performance of healthcare organizations. However, LSS in healthcare is also unbalanced because the human side of the method is undervalued. A more balanced application of LSS in healthcare includes an interrelated approach of both “soft” and “hard” LSS practices, broad perspective on employee well-being, “soft” HR approach related to LSS, and “soft” climate for LSS. This leads to a renewed perspective on LSS in healthcare that considers both people and performance and where the interplay between “hard” and “soft” factors is addressed

Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells

Contains fulltext : 76028.pdf (publisher's version ) (Open Access)8 p

Psychometric test of the Team Climate Inventory-short version investigated in Dutch quality improvement teams

Abstract BACKGROUND: Although some studies have used the Team Climate Inventory within teams working in health care settings, none of these included quality improvement teams. The aim of our study is to investigate the psychometric properties of the 14-item version of the Team Climate Inventory in healthcare quality improvement teams participating in a Dutch quality collaborative. METHODS: This study included quality improvement teams participating in the Care for Better improvement program for home care, care for the handicapped and the elderly in the Netherlands between 2006 and 2008. As part of a larger evaluation study 270 written questionnaires from team members were collected at baseline and 139 questionnaires at end measurement. Confirmatory factor analyses, reliability, Pearson correlations and paired samples t-tests were conducted to investigate construct validity, reliability, predictive validity and temporal stability. RESULTS: Confirmatory factor analyses revealed the expected four-factor structure and good fit indices. For the four subscales--vision, participative safety, task orientation and support for innovation--acceptable Cronbach's alpha coefficients and high inter-item correlations were found. The four subscales all proved significant predictors of perceived team effectiveness, with participatory safety being the best predictor. As expected the four subscales were found to be stable over time; i.e. without significant changes between baseline and end measurement. CONCLUSION: The psychometric properties of the Dutch version of the TCI-14 are satisfactory. Together these results show that the TCI-14 is a useful instrument to assess to what extent aspects of team climate influence perceived team effectiveness of quality improvement teams

Structure-activity relationship study of itraconazole, a broad-range inhibitor of picornavirus replication that targets oxysterol-binding protein (OSBP)

Itraconazole (ITZ) is a well-known, FDA-approved antifungal drug that is also in clinical trials for its anticancer activity. ITZ exerts its anticancer activity through several disparate targets and pathways. ITZ inhibits angiogenesis by hampering the functioning of the vascular endothelial growth receptor 2 (VEGFR2) and by indirectly inhibiting mTOR signaling. Furthermore, ITZ directly inhibits the growth of several types of tumor cells by antagonizing Hedgehog signaling. Recently, we reported that ITZ also has broad-spectrum antiviral activity against enteroviruses, cardioviruses and hepatitis C virus, independent of established ITZ-activities but instead via a novel target, oxysterol-binding protein (OSBP), a cellular lipid shuttling protein. In this study, we analyzed which structural features of ITZ are important for the OSBP-mediated antiviral activity. The backbone structure, consisting of five rings, and the sec-butyl chain are important for antiviral activity, whereas the triazole moiety, which is critical for antifungal activity, is not. The features required for OSBP-mediated antiviral activity of ITZ overlap mostly with published features required for inhibition of VEGFR2 trafficking, but not Hh signaling. Furthermore, we use in silico studies to explore how ITZ could bind to OSBP. Our data show that several pharmacological activities of ITZ can be uncoupled, which is a critical step in the development of ITZ-based antiviral compounds with greater specificity and reduced off-target effects