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Participants' use of enacted scenes in research interviews: A method for reflexive analysis in health and social care. - Social science & medicine (1982)
In our study of a workforce intervention within a health and social care context we found that participants who took part in longitudinal research interviews were commonly enacting scenes from their work during one-to-one interviews. Scenes were defined as portions of the interviews in which participants directly quoted the speech of at least two actors. Our analysis in this paper focuses on these enacted scenes, and compares the content of them before and after the intervention. We found that, whilst the tensions between consistency and change, and change management, were common topics for scene enactment in both pre and post-intervention data, following the intervention participants were much more likely to present themselves as active agents in that change. Post-intervention enacted scenes also showed participants' reports of taking a service user perspective, and a focus on their interactions with service users that had been absent from pre-intervention data. In addition, descriptions of positive feeling and emotions were present in the post-intervention enacted scenes. We suggest that this analysis confirms the importance of enacted scenes as an analytic resource, and that this importance goes beyond their utility in identifying the impact of this specific intervention. Given the congruence between the themes prominent in enacted scenes, and those which emerged from a more extensive qualitative analysis of these data, we argue that enacted scenes may also be of wider methodological importance. The possibility of using scene enactment as an approach to the validation of inductive analysis in health and social care settings could provide a useful methodological resource in settings where longitudinal ethnographic observation of frontline care staff is impossible or impractical.Copyright Â© 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2. - The American journal of pathology
The differentiation factor NEL-like molecule-1 (NELL-1) has been reported as osteoinductive in multiple inÂ vivo preclinical models. Bone morphogenetic protein (BMP)-2 is used clinically for skeletal repair, but inÂ vivo administration can induce abnormal, adipose-filled, poor-quality bone. We demonstrate that NELL-1 combined with BMP2 significantly optimizes osteogenesis in a rodent femoral segmental defect model by minimizing the formation of BMP2-induced adipose-filled cystlike bone. InÂ vitro studies using the mouse bone marrow stromal cell line M2-10B4 and human primary bone marrow stromal cells have confirmed that NELL-1 enhances BMP2-induced osteogenesis and inhibits BMP2-induced adipogenesis. Importantly, the ability of NELL-1 to direct BMP2-treated cells toward osteogenesis and away from adipogenesis requires intact canonical Wnt signaling. Overall, these studies establish the feasibility of combining NELL-1 with BMP2 to improve clinical bone regeneration and provide mechanistic insight into canonical Wnt pathway activity during NELL-1 and BMP2 osteogenesis. The novel abilities of NELL-1 to stimulate Wnt signaling and to repress adipogenesis may highlight new treatment approaches for bone loss in osteoporosis.Copyright Â© 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Workability and Requests for Flexible Work Arrangements Among Older Adults: The Role of a Time and Place Management Intervention. - Journal of applied gerontology : the official journal of the Southern Gerontological Society
This article investigates the effect of an intervention on the workability of older adults (i.e., the competence, health, and other mental and physical characteristics that workers need to meet the demands of their jobs). We used data from health care workers (N = 437) who participated in a "time and place management" (TPM) intervention. Although related to flexible work options that aim to give workers more choice and control over the time and place of their work, TPM is conceptually distinct in that it focuses on the processes and guidelines necessary to the successful management of choice and control rather than the options alone. We focused on how the TPM intervention moderated the relationship between age and workability over time, with a particular focus on variation by baseline workability. Our results indicated that the intervention can benefit older workers with low workability.Â© The Author(s) 2016.
Compound Heterozygous Triadin Mutation Causing Cardiac Arrest in Two Siblings. - Pacing and clinical electrophysiology : PACE
We present the case of 2 siblings who both presented with an out-of-hospital cardiac arrest at 2 years of age. Both siblings underwent ICD implantation and both had recurrent episodes of ventricular fibrillation. A compound heterozygous mutation in the triadin gene was discovered; one of these mutations has been described previously in the homozygous state, and the other one is unreported. The combination of these mutations has resulted in a particularly arrhythmogenic phenotype, with cardiac arrest occurring at a very young age and recurrent episodes of ventricular fibrillation despite Î²-blockade. Flecainide seems to have been very effective in preventing clinical arrhythmias for this particular mutation. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Blood cytotoxic/inflammatory mediators in non-eosinophilic asthma. - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Non-eosinophilic asthma (NEA) is a distinct, often corticosteroid-resistant inflammatory asthma phenotype. NK and NKT-like cells are effector lymphocytes that we have shown, like CD28null T cells, to be relatively resistant to steroids and major sources of pro-inflammatory/cytotoxic mediators. We hypothesized that these cells and mediators would be increased in peripheral blood in NEA.Adults with severe asthma and variable airflow obstruction, poorly controlled despite maintenance therapy with inhaled glucocorticosteroids and long-acting bronchodilators, were recruited. Blood was assessed in those with eosinophilic asthma (nÂ =Â 12), NEA (nÂ =Â 25) and healthy non-smoking controls (nÂ =Â 30). We applied flow cytometry to measure T, CD28null, NK and NKT-like cells and their expression of granzyme B, perforin, and killer inhibitory/activating receptors CD94(Kp43), CD158b and CD107A. Intracellular pro-inflammatory cytokine production (IFN-Î³ and TNF-Î±) was assessed in 18 controls and 10 patients with asthma/group.In NEA, there was increased expression of granzyme B by CD8+ T cells vs.There was increased expression of granzyme B and CD158 and decreased CD94 on NK cells, vs. healthy controls and those with eosinophilic asthma. IFN-Î³ production by NK cells and TNF-Î± production by NKT-like cells in NEA were significantly increased vs.In both eosinophilic and NEA phenotypes, there were significant increases in CD4+28null T cells (72% and 81% increases, respectively, vs. controls) and their expression of pro-inflammatory cytokines. Significant correlations were noted between blood CD4+28null T cells and neutrophil numbers in induced sputum, and between corticosteroid dose and blood NKT-like cells, and their production of granzyme B and TNF-Î± and NK IFN-Î³.In poorly controlled asthma, altered expression of cytotoxic/pro-inflammatory mediators can be seen on a variety of lymphocyte subsets in the peripheral blood; these changes are most apparent in NEA. Whether this pattern of expression is a marker of treatment responsiveness and future risk of exacerbations remains to be determined.Â© 2015 John Wiley & Sons Ltd.
Care-limiting decisions in acute stroke and association with survival: analyses of UK national quality register data. - International journal of stroke : official journal of the International Stroke Society
Prognosis after intracerebral hemorrhage (ICH) is poor and care-limiting decisions may worsen outcomes.To determine whether in current UK stroke practice, key acute care decisions are associated with stroke subtype (ICH/ischemic) and whether these decisions are independently associated with survival.We extracted data describing all stroke patients included in a UK quality register between 1 April 2013 and 31 March 2014. Key care decisions in our analyses were transfer to higher level care on admission and palliation in the first 72â€‰h. We used multivariable regression models to test for associations between stroke subtype (ICH/ischemic), key care decisions, and survival.A total of 65,818 patients were included in the final analysis. After ICH (nâ€‰=â€‰7020/65,818, 10.7%), 10.5% were palliated on the day of admission and 19.3% by 72â€‰h (vs. 0.7% and 3.3% for ischemic stroke). Although a greater proportion were admitted directly to higher level care after ICH (3.7% vs. 1.5% for ischemic stroke), ICH was not independently associated with the decision to admit to higher level care (adjusted odds ratio (OR): 1.12, 95% confidence interval (95%CI): 0.95-1.31, pâ€‰=â€‰0.183). However, ICH was strongly associated with the decision to commence palliative care on the day of admission (OR: 7.27, 95%CI: 6.31-8.37, pâ€‰<â€‰0.001). Palliative care was independently associated with risk of death by 30 days regardless of stroke subtype.When compared to ischemic stroke, patients with ICH are much more likely to commence palliative care during the first 72â€‰h of their care, independent of level of consciousness, age, and premorbid health.Â© 2016 World Stroke Organization.
Reduced interleukin-2 responsiveness impairs the ability of Treg cells to compete for IL-2 in nonobese diabetic mice. - Immunology and cell biology
Enhancement of regulatory T cell (Treg cell) frequency and function is the goal of many therapeutic strategies aimed at treating type 1 diabetes (T1D). The IL-2 pathway, which has been strongly implicated in T1D susceptibility in both humans and mice, is a master regulator of Treg cell homeostasis and function. We investigated how IL-2 pathway defects impact Treg cells in T1D susceptible nonobese diabetic (NOD) mice in comparison to protected C57BL/6 and NOD congenic mice. NOD Treg cells were reduced in frequency specifically in the lymph nodes and expressed lower levels of CD25 and CD39/CD73 immunosuppressive molecules. In the spleen and blood, Treg cell frequency was preserved through expansion of CD25(low), effector phenotype Treg cells. Reduced CD25 expression led to decreased IL-2 signaling in NOD Treg cells. In vivo, treatment with IL-2-anti-IL-2 antibody complexes led to effective upregulation of suppressive molecules on NOD Treg cells in the spleen and blood, but had reduced efficacy on lymph node Treg cells. In contrast, NOD CD8(+) and CD4(+) effector T-cells were not impaired in their response to IL-2 therapy. We conclude that NOD Treg cells have an impaired responsiveness to IL-2 that reduces their ability to compete for a limited supply of IL-2.Immunology and Cell Biology accepted article preview online, 14 January 2016. doi:10.1038/icb.2016.7.
Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes. - Stem cells (Dayton, Ohio)
Rodent-based studies have shown that the membrane properties of oligodendrocytes play prominent roles in their physiology and shift markedly during their maturation from the oligodendrocyte precursor cell (OPC) stage. However, the conservation of these properties and maturation processes in human oligodendrocytes remains unknown, despite their dysfunction being implicated in human neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Here, we have defined the membrane properties of human oligodendrocytes derived from pluripotent stem cells as they mature from the OPC stage, and have identified strong conservation of maturation-specific physiological characteristics reported in rodent systems. We find that as human oligodendrocytes develop and express maturation markers, they exhibit a progressive decrease in voltage-gated sodium and potassium channels and a loss of tetrodotoxin-sensitive spiking activity. Concomitant with this is an increase in inwardly rectifying potassium channel activity, as well as a characteristic switch in AMPA receptor composition. All these steps mirror the developmental trajectory observed in rodent systems. Oligodendrocytes derived from mutant C9ORF72-carryng ALS patient induced pluripotent stem cells did not exhibit impairment to maturation and maintain viability with respect to control lines despite the presence of RNA foci, suggesting that maturation defects may not be a primary feature of this mutation. Thus, we have established that the development of human oligodendroglia membrane properties closely resemble those found in rodent cells and have generated a platform to enable the impact of human neurodegenerative disease-causing mutations on oligodendrocyte maturation to be studied. Stem Cells 2016.Â© 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43. - Cardiovascular research
Increasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDL). HDL binding to receptors at the surface of cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate the pathways by which the Sphingosine-1-Phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischemia/reperfusion (I/R).Apolipoprotein M (ApoM) transgenic (Apom-Tg) mice, in which plasma S1P is increased by 296%, and wild-type (WT) mice were subjected to in vivo I/R. Infarct size, neutrophil infiltration into the infarcted area and serum Troponin I were less pronounced in Apom-Tg mice. In vitro experiments suggest that this cardioprotection depends on direct effects of S1P on cardiomyocytes, whereas leukocyte recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce ischemia/reperfusion injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap junction protein Connexin43 (Cx43) on Serine368, which was mediated by S1P2 and S1P3, but not by S1P1, receptors in cardiomyocytes. Finally, S1P-induced reduction of infarct size after ex vivo I/R was lost in hearts of mice with a truncated C-terminus of Cx43 (Cx43(K258/KO)) or in which the Serine368 is mutated to a non-phosphorylatable Alanine (Cx43(S368A/S368A)).Our study reveals an important molecular pathway by which modulating the apoM/S1P axis has a therapeutic potential in the fight against ischemia/reperfusion injury in the heart.Published on behalf of the European Society of Cardiology. All rights reserved. Â© The Author 2016. For permissions please email: firstname.lastname@example.org.
Acute necrotising encephalopathy in a child with H1N1 influenza infection: a clinicoradiological diagnosis and follow-up. - BMJ case reports
Acute necrotising encephalopathy of childhood (ANEC) is a fulminant disorder with rapid progressive encephalopathy, seizures and poor outcome. It has been reported in association with various viral infections. We describe the clinicoradiological findings and short-term follow-up in a child with H1N1 influenza-associated ANEC. Laminar, target or tricolour pattern of involvement of the thalami was seen on apparent diffusion coefficient images. Our patient had significant morbidity at discharge despite early diagnosis and management with oseltamivir and immunoglobulin. Repeat imaging after 3â€…months had shown significant resolution of thalamic swelling, but there was persistence of cytotoxic oedema involving bilateral thalami. She was pulsed with intravenous steroids and maintained on a tapering schedule of oral steroids. This report emphasises the need for a high index of suspicion to establish early diagnosis, promotion of widespread immunisation strategies to prevent influenza outbreak, and more research to establish standard treatment protocols for this under-recognised entity.2016 BMJ Publishing Group Ltd.
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