36 research outputs found

    Outsiders in the Experts’ World: A Grounded Theory Study of Consumers and the Social World of Health Care

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    © The Author(s) 2020. This article presents findings from a grounded theory study, which investigated interactions between health professionals and consumers. The authors used Corbin and Strauss’s evolved version of grounded theory, which is underpinned by symbolic interactionism. The study sample included 23 consumers and nine health professionals. Data collection methods included demographic questionnaires, interviews, consumer diaries, digital storytelling, observations, and field notes. Data analysis was conducted using essential grounded theory methods. The resultant grounded theory consists of five categories: (a) Unexpected entrance, (b) Learning a new role, (c) Establishing a presence, (d) Confronting the dichotomy of “us and them,” and (e) Tailored care. Findings suggest that despite consumers and health professionals’ roles, consumers are outsiders in the social world of health care. Progress toward empowered consumers who are in control of their health and health care is slow and care that is truly consumer-centered is still the exception not the rule

    The C-terminal domain of zDHHC2 contains distinct sorting signals that regulate intracellular localisation in neurons and neuroendocrine cells

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    The S-acyltransferase zDHHC2 mediates dynamic S-acylation of PSD95 and AKAP79/150, which impacts synaptic targeting of AMPA receptors. zDHHC2 is responsive to synaptic activity and catalyses the increased S-acylation of PSD95 that occurs following action potential blockade or application of ionotropic glutamate receptor antagonists. These treatments have been proposed to increase plasma membrane delivery of zDHHC2 via an endosomal cycling pathway, enhancing substrate accessibility. To generate an improved understanding of zDHHC2 trafficking and how this might be regulated by neuronal activity, we searched for intramolecular signals that regulate enzyme localisation. Two signals were mapped to the C-terminal tail of zDHHC2: a non-canonical dileucine motif [SxxxLL] and a downstream NP motif. Mutation of these signals enhanced plasma membrane accumulation of zDHHC2 in both neuroendocrine PC12 cells and rat hippocampal neurons, consistent with reduced endocytic retrieval. Furthermore, mutation of these signals also increased accumulation of the enzyme in neurites. Interestingly, several threonine and serine residues are adjacent to these sorting motifs and analysis of phospho-mimetic mutants highlighted a potential role for phosphorylation in regulating the efficacy of these signals. This study offers new molecular insight into the signals that determine zDHHC2 localisation and highlights a potential mechanism to regulate these trafficking signals

    Regional and developmental brain expression patterns of SNAP25 splice variants

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    SNAP25 is an essential SNARE protein for regulated exocytosis in neuronal cells. Differential splicing of the SNAP25 gene results in the expression of two transcripts, SNAP25a and SNAP25b. These splice variants differ by only 9 amino acids, and studies of their expression to date have been limited to analysis of the corresponding mRNAs. Although these studies have been highly informative, it is possible that factors such as differential turnover of the SNAP25 proteins could complicate interpretations based entirely on mRNA expression profiles

    Neuromuscular synaptic transmission in aged ganglioside-deficient mice

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    Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 degrees C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. (C) 2009 Elsevier Inc. All rights reserve

    Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion

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    Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0

    Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43.

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    Phosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43

    The academy for future science faculty:randomized controlled trial of theory-driven coaching to shape development and diversity of early-career scientists

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    Background: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level. Explanations for the absence of diversity in faculty ranks can be found in social science theories that reveal processes by which individuals develop identities, experiences, and skills required to be seen as legitimate within the profession. Methods/Design: Using the social science theories of Communities of Practice, Social Cognitive Career Theory, identity formation, and cultural capital, we have developed and are testing a novel coaching-based model to address some of the limitations of previous diversity approaches. This coaching intervention (The Academy for Future Science Faculty) includes annual in-person meetings of students and trained faculty Career Coaches, along with ongoing virtual coaching, group meetings and communication. The model is being tested as a randomized controlled trial with two cohorts of biomedical PhD students from across the U.S., one recruited at the start of their PhDs and one nearing completion. Stratification into the experimental and control groups, and to coaching groups within the experimental arms, achieved equal numbers of students by race, ethnicity and gender to the extent possible. A fundamental design element of the Academy is to teach and make visible the social science principles which highly influence scientific advancement, as well as acknowledging the extra challenges faced by underrepresented groups working to be seen as legitimate within the scientific communities. Discussion: The strategy being tested is based upon a novel application of the well-established principles of deploying highly skilled coaches, selected and trained for their ability to develop talents of others. This coaching model is intended to be a complement, rather than a substitute, for traditional mentoring in biomedical research training, and is being tested as such

    Sharing success – understanding barriers and enablers to secondary prophylaxis delivery for rheumatic fever and rheumatic heart disease

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    BACKGROUND: Rheumatic fever (RF) and rheumatic heart disease (RHD) cause considerable morbidity and mortality amongst Australian Aboriginal and Torres Strait Islander populations. Secondary antibiotic prophylaxis in the form of 4-weekly benzathine penicillin injections is the mainstay of control programs. Evidence suggests, however, that delivery rates of such prophylaxis are poor. METHODS: This qualitative study used semi-structured interviews with patients, parents/care givers and health professionals, to explore the enablers of and barriers to the uptake of secondary prophylaxis. Data from participant interviews (with 11 patients/carers and 11 health practitioners) conducted in four far north Queensland sites were analyzed using the method of constant comparative analysis. RESULTS: Deficits in registration and recall systems and pain attributed to injections were identified as barriers to secondary prophylaxis uptake. There were also varying perceptions regarding responsibility for ensuring injection delivery. Enablers of secondary prophylaxis uptake included positive patient-healthcare provider relationships, supporting patient autonomy, education of patients, care givers and healthcare providers, and community-based service delivery. CONCLUSION: The study findings provide insights that may facilitate enhancement of secondary prophylaxis delivery systems and thereby improve uptake of secondary prophylaxis for RF/RHD

    Practice nurses and cervical screening: A two-country review

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    The aim of this review is to explore the literature relating to the delivery of cervical screening by practice nurses (PNs) in the United Kingdom and Australia. Research relating to PNs began in earnest approximately 15 years ago in the UK context, and more recently, c.2005, in Australia. Although there is scant literature devoted specifically to the role of PNs in cervical screening, literature relating to the role of PNs provides evidence of the extent to which PNs in the United Kingdom and Australia are involved in the provision of cervical screening services. Findings from this review indicate that the role of PNs in the provision of cervical screening differs substantially between the United Kingdom and Australia. PNs in the United Kingdom provide a high percentage of cervical screening services, whereas in Australia general practitioners provide around 80% of all cervical smears, which account for only 0.6% of all procedures undertaken by PNs. Employment and funding models and inadequate multidisciplinary collaboration are contributing to the underutilization of PNs in Australia

    Nurses in Australian acute care settings: experiences with and outcomes of e-health. An integrative review

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    The World Health Organization (WHO) defines e-health as the "use of information and communication technology for health". The use of e-health, including electronic medical records (EMR), is a growing trend. This integrative review of the literature examines nurses' experiences of e-health in Australian acute care settings. A search of the literature identified 21 papers for inclusion in this review. Two discernable themes in the literature are apparent. Research to date largely focuses on nurses' experiences of e-health, including its usefulness in their work. Findings indicate that nurses' attitudes to e-health and computer usage are positive, however there are indications that nurses currently using e-health in practice are often dissatisfied with the implementation of new e-health systems in their workplace and that there are a number of barriers to its successful implementation. Secondly, a discernable gap in the literature regarding the impact of e-health, and in particular EMRs, on nursing outcomes is identified with research to date limited to findings related to nursing documentation and multi-disciplinary discharge planning. Future research that considers nurses' experiences in implementing e-health and applies focused strategies across a range of health settings, both in Australia and around the world, can influence successful adoption and implementation of e-health
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