Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multifactorial and remain unclear. Here we examined DNA damage;p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93) --> Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2`-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This toxic activity of mutant SOD1 in the nucleus may play an important role in the complex mechanisms associated with motor neuron death observed in ALS pathogenesis. (C) 2010 Elsevier B.V. All rights reserved.

Health and quality of care from older peoples' and formal caregivers' perspective

Aim: The overall aim of this thesis was to gain a deeper understanding of older people's view of health and care while dependent on community care. Furthermore to describe and compare formal caregivers' perceptions of quality of care, working conditions, competence, general health, and factors associated with quality of care from the caregivers' perspective. Method: Qualitative interviews were conducted with 19 older people in community care who were asked to describe what health and ill health((I), good and bad care meant for them (II). Data were analyzed using content analysis (I) and a phenomenological analysis (II). The formal caregivers; 70 nursing assistants (NAs) 163 enrolled nurses (ENs) and 198 registered nurses (RNs), answered a questionnaire consisting of five instruments: quality of care from the patient's perspective modified to formal caregivers, creative climate questionnaire, stress of conscience, health index, sense of coherence and items on education and competence (III). Statistical analyses were performed containing descriptive statistics, and comparisons between the occupational groups were made using Kruskal-Wallis ANOVA, Mann-Whitney U-test and Pearson's Chi-square test (III). Pearson's  product moment correlation analysis and multiple regression analysis were performed studying the associations between organizational climate, stress of conscience, competence, general health and sense of coherence with quality of care (IV). Results: The older people's health and well-being were related to their own ability to adapt to and compensate for their disabilities and was described as negative and positive poles of autonomy vs. dependence, togetherness vs. being an onlooker, security vs. insecurity and tranquility vs. disturbance (I).  The meaning of good care (II) was that the formal caregivers respected the older people as unique individuals, having the opportunity to live their lives as usual and receiving a safe and secure care. Good care could be experienced when the formal caregivers had adequate knowledge and competence in caring for older people, adequate time and continuity in the care organization (II). Formal caregivers reported higher perceived quality of care in the dimensions medical-technical competence and physical-technical conditions than in identity-oriented approach and socio-cultural atmosphere (III). In the organizational climate three of the dimensions were close to the value of a creative climate and in seven near a stagnant climate. The formal caregivers reported low rate of stress of conscience. The RNs reported to a higher degree than the NAs/ENs a need to gain more knowledge, but the NAs and the ENs more often received training during working hours. The RNs reported lower emotional well-being than the NAs/ENs (III). The formal caregivers' occupation, organizational climate and stress of conscience were associated with perceived quality of care (IV). Implications: The formal caregivers should have an awareness of the importance of kindness and respect, supporting the older people to retain control over their lives. The nursing managers should employ highly competent and adequate numbers of skilled formal caregivers, organize formal caregivers having round the clock continuity. Improvements of organizational climate and stress of conscience are of importance for good quality of care.

Push or pull? : The relationship between quality of care and use of complementary and alternative medicine among patients with lung cancer in Sweden

Little is known about relationships between quality of care (QoC) and use of complementary and alternative medicine (CAM) among patients with lung cancer (LC). Purpose: This study examines CAM-use among patients with LC in Sweden, associations between QoC and CAM-use among these patients, and reported aspects of LC-care perceived as particularly positive and negative by patients, as well as suggestions for improving QoC. Methods: Survey data from 94 patient members of the Swedish LC patient organization about CAM-use and QoC as measured by the instrument “Quality from the patient’s perspective” were analyzed. Results: Fifty (53%) LC-patients used CAM, with 40 of the CAM-users reporting that CAM helped them. The most common CAMs used were dietary supplements and natural remedies, followed by prayer. Significantly more patients reported using prayer and meditation for cure than was the case for other types of CAM used. Less than half the CAM-users reported having spoken with staff from the biomedical health care system about their CAM-use. Patients provided numerous suggestions for improving LC-care in a variety of areas, aiming at a more effective and cohesive care trajectory. No differences in QoC were found between CAM-users and non-CAM-users, but differences in CAM-use i.e. type of CAM, reasons for using CAM, and CAM-provider consulted could be associated with different experiences of care. Conclusions: It is important to recognize that CAM-users are not a homogeneous group but might seek different types of CAMs and CAM-providers in different situations depending on experiences of care.

Formal caregivers' perceptions of quality of care for older people : associating factors

Background: Despite the growing number of studies concerning quality of care for older people, there is a lack of studies depicting factors associated with good quality of care from the formal caregivers' perspective. The aim was to describe formal caregivers' perceptions of quality of care for older people in the community and explore factors associated with these perceptions. In total, 70 nursing assistants, 163 enrolled nurses and 198 registered nurses from 14 communities in central Sweden participated in the study. They filled out the following questionnaires: a modified version of Quality from the Patient's Perspective, Creative Climate Questionnaire, Stress of Conscience Questionnaire, items regarding education and competence, Health Index and Sense of coherence questionnaire. The overall response rate was 57 % (n = 431). Results: In the perceived reality of quality of care respondents assessed the highest mean value in the dimension medical-technical competence and physical technical conditions and lower values in the dimensions; identity-oriented approach, socio-cultural atmosphere and in the context specific dimension. The caregivers estimated their competence and health rather high, had lower average values in sense of coherence and organizational climate and low values in stress of conscience. Conculsions: The PR of quality of care were estimated higher among NA/ENs compared to RNs. Occupation, organizational climate and stress of conscience were factors associated with quality of care that explained 42 % of the variance. Competence, general health and sense of coherence were not significantly associated to quality of care. The mentioned factors explaining quality of care might be intertwined and showed that formal caregivers' working conditions are of great importance for quality of care.

Depicting the interplay between organisational tiers in the use of a national quality registry to develop quality of care in Sweden

BACKGROUND: With a pending need to identify potential means to improved quality of care, national quality registries (NQRs) are identified as a promising route. Yet, there is limited evidence with regards to what hinders and facilitates the NQR innovation, what signifies the contexts in which NQRs are applied and drive quality improvement. Supposedly, barriers and facilitators to NQR-driven quality improvement may be found in the healthcare context, in the politico-administrative context, as well as with an NQR itself. In this study, we investigated the potential variation with regards to if and how an NQR was applied by decision-makers and users in regions and clinical settings. The aim was to depict the interplay between the clinical and the politico-administrative tiers in the use of NQRs to develop quality of care, examining an established registry on stroke care as a case study. METHODS: We interviewed 44 individuals representing the clinical and the politico-administrative settings of 4 out of 21 regions strategically chosen for including stroke units representing a variety of outcomes in the NQR on stroke (Riksstroke) and a variety of settings. The transcribed interviews were analysed by applying The Consolidated Framework for Implementation Research (CFIR). RESULTS: In two regions, decision-makers and/or administrators had initiated healthcare process projects for stroke, engaging the health professionals in the local stroke units who contributed with, for example, local data from Riksstroke. The Riksstroke data was used for identifying improvement issues, for setting goals, and asserting that the stroke units achieved an equivalent standard of care and a certain level of quality of stroke care. Meanwhile, one region had more recently initiated such a project and the fourth region had no similar collaboration across tiers. Apart from these projects, there was limited joint communication across tiers and none that included all individuals and functions engaged in quality improvement with regards to stroke care. CONCLUSIONS: If NQRs are to provide for quality improvement and learning opportunities, advances must be made in the links between the structures and processes across all organisational tiers, including decision-makers, administrators and health professionals engaged in a particular healthcare process.

A Model of Normative Power

A power describes the ability of an agent to act in some way. While this notion of power is critical in the context of organisational dynamics, and has been studied by others in this light, it must be constrained so as to be useful in any practical application. In particular, we are concerned with how power may be used by agents to govern the imposition and management of norms, and how agents may dynamically assign norms to other agents within a multi-agent system. We approach the problem by defining a syntax and semantics for powers governing the creation, deletion, or modification of norms within a system, which we refer to as normative powers. We then extend this basic model to accommodate more general powers that can modify other powers within the system, and describe how agents playing certain roles are able to apply powers, changing the system’s norms, and also the powers themselves. We examine how the powers found within a system may change as the status of norms change, and show how standard norm modification operations — such as the derogation, annulment and modification of norms— may be represented within our system.