Senior Citizens, Good Practice and Quality of Life in Residential Care Homes

This thesis is an examination of the definition and implementation of ‘good practice’ in residential care for senior citizens. The central contention is that ‘good practice’ is a term that has been variously defined. Different groups define it in different ways, and their definitions have changed over time. This reflexive qualitative study explores ‘good practice’ in local authority, voluntary and private residential care homes in Scotland from the perspective of policy, practice and the experience of senior citizens who live in them. The study is based on analysis of policy documents, historical studies, and reanalysed interview and survey data from two earlier studies conducted by the author and colleagues. The thesis shows that the notion of ‘good practice’ that emerges in policy and practice documents is a confused and often conflicting set of ideas. Historically, the earliest were driven by concerns over cost. In more modern times, statements about ‘good practice’ have had a more benevolent intent but are frequently flawed by paternalistic and ageist assumptions. It is shown that staff in residential homes typically adopt a different set of attitudes: their preoccupation is with safety and the avoidance of risk. Although benevolent in intention, these interpretations of ‘good practice’ are also at variance with what residents themselves actually want. Two particular models or styles of care are examined in detail. One of these is the use of ‘keyworkers’, often implemented in ways that fail to realise its potential. The other is the ‘hotel’ model of care. The potential of this model as an alternative to the statutory model is explored. The thesis concludes that it is a model that can realise the goal of enabling residents to exercise independence, choice and privacy while meeting their needs in residential care

SGK1 in the kidney: disrupted sodium transport in diabetes and beyond

Renal complications of diabetes can be severe; however, the mechanisms that underlie the development and progression of diabetic nephropathy are poorly understood. Recent evidence suggests that the serum and glucocorticoid induced kinase-1 (SGK1) may be key to this process. SGK1 expression and function are increased in models of diabetes and polymorphisms of the SGK1 gene are associated with type 2 diabetes mellitus. A key regulator of sodium transport within the renal epithelium of the distal nephron, SGK1 was originally isolated as a glucocorticoid-sensitive gene that regulated the epithelial sodium channel (ENaC; known also as the sodium channel, nonvoltage-gated 1, SCNN1). It is now apparent that SGK1 modulates sodium re-absorption by a number of sodium transporters/channels throughout the length of the nephron including; the Na+/H+ exchange isoform 3 (NHE3), the Na+Cl- co-transporter (NCC) and the Na+/K+-ATPase. In addition, SGK1 is regulated by a diverse range of factors including; insulin, glucose, intracellular calcium, transforming growth factor-beta1, flow rate and osmolality. This brief review examines the evidence supporting an involvement of SGK1 in diabetic nephropathy and discusses how dysregulated sodium transport may account for the development of secondary hypertension associated with the condition. Furthermore, the article examines how aberrant SGK1 expression and activity may be responsible for the cellular changes seen in the damaged nephron

Functional expression of TRPV4 channels in human collecting duct cells: implications for secondary hypertension in diabetic nephropathy

Background. The Vanilloid subfamily of transient receptor potential (TRPV) ion channels has been widely implicated in detecting osmotic and mechanical stress. In the current study, we examine the functional expression of TRPV4 channels in cell volume regulation in cells of the human collecting duct. Methods. Western blot analysis, siRNA knockdown, and microfluorimetry were used to assess the expression and function of TRPV4 in mediating Ca2+-dependent mechanical stimulation within a novel system of the human collecting duct (HCD). Results. Native and siRNA knockdown of TRPV4 protein expression was confirmed by western blot analysis. Touch was used as a cell-directed surrogate for osmotic stress. Mechanical stimulation of HCD cells evoked a transient increase in [Ca2+]i that was dependent upon thapsigargin-sensitive store release and Ca2+ influx. At 48 hrs, high glucose and mannitol (25 mM) reduced TRPV4 expression by 54% and 24%, respectively. Similar treatment doubled SGK1 expression. Touch-evoked changes were negated following TRPV4 knockdown. Conclusion. Our data confirm expression of Ca2+-dependent TRPV4 channels in HCD cells and suggest that a loss of expression in response to high glucose attenuates the ability of the collecting duct to exhibit regulatory volume decreases, an effect that may contribute to the pathology of fluid and electrolyte imbalance as observed in diabetic nephropathy

Senior citizens, good practice and quality of life in residential care homes

This thesis is an examination of the definition and implementation of ‘good practice’ in residential care for senior citizens. The central contention is that ‘good practice’ is a term that has been variously defined. Different groups define it in different ways, and their definitions have changed over time. This reflexive qualitative study explores ‘good practice’ in local authority, voluntary and private residential care homes in Scotland from the perspective of policy, practice and the experience of senior citizens who live in them. The study is based on analysis of policy documents, historical studies, and reanalysed interview and survey data from two earlier studies conducted by the author and colleagues. The thesis shows that the notion of ‘good practice’ that emerges in policy and practice documents is a confused and often conflicting set of ideas. Historically, the earliest were driven by concerns over cost. In more modern times, statements about ‘good practice’ have had a more benevolent intent but are frequently flawed by paternalistic and ageist assumptions. It is shown that staff in residential homes typically adopt a different set of attitudes: their preoccupation is with safety and the avoidance of risk. Although benevolent in intention, these interpretations of ‘good practice’ are also at variance with what residents themselves actually want. Two particular models or styles of care are examined in detail. One of these is the use of ‘keyworkers’, often implemented in ways that fail to realise its potential. The other is the ‘hotel’ model of care. The potential of this model as an alternative to the statutory model is explored. The thesis concludes that it is a model that can realise the goal of enabling residents to exercise independence, choice and privacy while meeting their needs in residential care.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Extracellular calcium-sensing receptor mediated signalling is involved in human vascular smooth muscle cell proliferation and apoptosis

Calcium-sensing receptor (CaSR) plays key role in vascular calcification in patients with chronic kidney disease (CKD). We investigated the role of CaSR in regulating smooth muscle cell (SMC) proliferation and apoptosis. Incubation with 300µM neomycin (CaSR agonist) resulted in 7.5-fold (p3-fold, which was reduced in CaSR knockdown cells (p<0.01) and further inhibited by PD98059 and U73122 (p<0.05). Apoptosis was not affected by neomycin treatment. U73122 produced 3.5-fold increase in HAoSMC apoptosis, which was further increased by CaSR knockdown (5-fold, p<0.05). In conclusion, stimulation of CaSR leads to activation of MEK1/ERK1,2 and PLC pathways and up-regulation of cell proliferation. CaSR-mediated PLC activation is important for SMC survival and protection against apoptosis

Calcium-sensing receptor in artery

UNLABELLED: Vascular calcification (VC) is common in chronic kidney disease (CKD) and contributes to cardiovascular mortality. The calcium-sensing receptor (CaSR) is present in human artery, senses extracellular calcium and may directly modulate VC. OBJECTIVE: to investigate the association between arterial cyclic strain, CaSR expression and VC. METHODS AND RESULTS: human aortic smooth muscle cells (HAoSMC) were cultured under static or strained conditions, with exposure to CaSR agonists, the calcimimetic R568, and after CaSR silencing and over-expression. High extracellular calcium reduced CaSR expression and promoted osteochondrogenic transformation and calcium deposition. This was partially prevented by cyclic strain and exposure to R568. CaSR silencing enhanced calcification and osteochondrogenic transformation, whereas CaSR over-expression attenuated this procalcific response, demonstrating a central role for the CaSR in the response to cyclic strain and regulation of VC. In arterial explants from CKD patients (n = 11) and controls (n = 9), exposure to R568 did not significantly alter calcium deposition, osteochondrogenic markers or total artery calcium content. CONCLUSIONS: physiological mechanical strain is important for arterial homeostasis and may protect arteries from VC. The beneficial effects of cyclic strain may be mediated via the CaSR.We are grateful to Professor A.R. Bradwell (Binding Site) for generating CaSR antibody and MRC Infrastructure Award (G4500017) 'Bioinformatics and Structural Biology in Life Sciences' for CaSR peptide design. R-568 and S-568 was a kind gift from Amgen USA.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.013883

High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

Impaired arterial vitamin D signaling occurs in the development of vascular calcification.

Funder: Abbott Laboratories; funder-id: http://dx.doi.org/10.13039/100001316Conflicting data exists as to whether vitamin D receptor agonists (VDRa) are protective of arterial calcification. Confounding this, is the inherent physiological differences between human and animal experimental models and our current fragmented understanding of arterial vitamin D metabolism, their alterations in disease states and responses to VDRa's. Herein, the study aims to address these problems by leveraging frontiers in human arterial organ culture models. Human arteries were collected from a total of 24 patients (healthy controls, n = 12; end-stage CKD, n = 12). Cross-sectional and interventional studies were performed using arterial organ cultures treated with normal and calcifying (containing 5mmol/L CaCl2 and 5mmol/L β-glycerophosphate) medium, ex vivo. To assess the role of VDRa therapy, arteries were treated with either calcitriol or paricalcitol. We found that human arteries express a functionally active vitamin D system, including the VDR, 1α-hydroxylase and 24-hydroxylase (24-OHase) components and these were dysregulated in CKD arteries. VDRa therapy increased VDR expression in healthy arteries (p<0.01) but not in CKD arteries. Arterial 1α-OHase (p<0.05) and 24-OHase mRNA and protein expression were modulated differentially in healthy and CKD arteries by VDRa therapy. VDRa exposure suppressed Runx2 and MMP-9 expression in CKD arteries, however only paricalcitol suppressed MMP-2. VDRa exposure did not modulate arterial calcification in all organ culture models. However, VDRa reduced expression of senescence associated β-galactosidase (SAβG) staining in human aortic-smooth muscle cells under calcifying conditions, in vitro. In conclusion, maladaptation of arterial vitamin D signaling components occurs in CKD. VDRa exposure can exert vasculo-protective effects and seems critical for the regulation of arterial health in CKD

The K2-HERMES Survey: Age and Metallicity of the Thick Disc

Asteroseismology is a promising tool to study Galactic structure and evolution because it can probe the ages of stars. Earlier attempts comparing seismic data from the {\it Kepler} satellite with predictions from Galaxy models found that the models predicted more low-mass stars compared to the observed distribution of masses. It was unclear if the mismatch was due to inaccuracies in the Galactic models, or the unknown aspects of the selection function of the stars. Using new data from the K2 mission, which has a well-defined selection function, we find that an old metal-poor thick disc, as used in previous Galactic models, is incompatible with the asteroseismic information. We show that spectroscopic measurements of [Fe/H] and [$\alpha$/Fe] elemental abundances from the GALAH survey indicate a mean metallicity of $\log (Z/Z_{\odot})=-0.16$ for the thick disc. Here $Z$ is the effective solar-scaled metallicity, which is a function of [Fe/H] and [$\alpha$/Fe]. With the revised disc metallicities, for the first time, the theoretically predicted distribution of seismic masses show excellent agreement with the observed distribution of masses. This provides an indirect verification of the asteroseismic mass scaling relation is good to within five percent. Using an importance-sampling framework that takes the selection function into account, we fit a population synthesis model of the Galaxy to the observed seismic and spectroscopic data. Assuming the asteroseismic scaling relations are correct, we estimate the mean age of the thick disc to be about 10 Gyr, in agreement with the traditional idea of an old $\alpha$-enhanced thick disc.Comment: 21 pages, submitted to MNRA