Family carers' perspectives of managing activities of daily living and use of mHealth applications in dementia care: A qualitative study

Calleja, P ORCiD: 0000-0001-5674-1404Aim: To examine the needs, barriers and challenges experienced by family carers of people with dementia concerning the management of their care recipients' functional disabilities, and their experiences and opinions of using mobile health (mHealth) applications in health information seeking. Background: Functional disability is a significant problem among people with dementia and management can be challenging for family carers. Evidence suggests that mHealth applications can support knowledge needs of patients and families. Design: A qualitative descriptive exploratory study. Methodology: In-depth interviews were conducted with a purposive sample of family carers using a semi-structured interview guide. An inductive thematic analysis method was used. The COREQ reporting guideline was followed. Results: Five spousal and five child carers participated in this study. Four key themes were identified: (a) Challenges faced that contribute to psychological distress and burden; (b) Essential role of support systems in dementia care; (c) Information and educational needs of family carers, and (d) Experiences and attitudes of mHealth applications as an educational and supportive resource. Conclusion: Providing functional care is demanding, challenging and stressful, and leads to carer burden. The complexity of dementia is a barrier in the organisation of functional care and access to a support network is vital to care provision. The information needs of family carers can potentially be addressed through an mHealth application. Relevance to clinical practice: This study provides important information on family carers' needs, and the barriers and challenges related to functional care for people with dementia. Findings from this study can assist nurses and other health professionals in the planning of educational and supportive programs for family carers. Furthermore, the use of mHealth applications could positively contribute to the delivery of these programs. © 2019 John Wiley & Sons Lt

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Knowledge and awareness of the general public and perception of pharmacists about antibiotic resistance

Background Antibiotic resistance (AR) continues to be a serious problem. Many factors contribute to AR, including inappropriate use of antibiotics, in which both healthcare professionals and patients play a contributing role. This study aimed to assess the awareness and knowledge of antibiotic usage and AR among the general public (in affluent and deprived areas) and community pharmacists' (CPs') in Greater London. Methods A cross-sectional survey involving members of the public was conducted between July 2014 and February 2015. Stage one involved members of the public (N = 384) residing in affluent areas of London. The second stage targeted public (N = 384) in deprived areas of London. In addition, CPs (N = 240) across the same areas were also surveyed. Data analysis was performed using Microsoft Excel and SPSS Software packages. Results Response rate: 36% (n = 139/384) and 57% (n = 220/384) and 25% (n = 60/240) of public residing in affluent areas, deprived areas and of CPs respectively was achieved. Definitive trends in knowledge of how antibiotics work could not be drawn to distinguish between affluent and deprived areas. However, public respondents residing in affluent areas possessed better understanding of AR and prudent use of antibiotics, and this was statistically significant in both cases (p < 0.05). Exposure to an antibiotic campaign (32% in affluent areas, 17% in deprived areas) did not raise public respondents' knowledge on AR and only partially raised their general knowledge on antibiotics usage. Only 20% of public residing in deprived areas received counselling from a CP, among them 74% had an antibiotic prescribed on at least one previous occasion. Those who received counselling displayed better knowledge about concordance/adherence with respect to antibiotic usage (p < 0.05) whereas exposure to an antibiotic campaign made no significant impact on knowledge about concordance/adherence. Conclusion The study highlights that there has been no change in the status quo with respect to awareness of antibiotic usage and AR even after the implementation of several awareness campaigns in England. Those who benefited from CP counselling showed a significant better knowledge towards prudent antibiotic usage which stresses the importance of CPs' counselling on antibiotic prescription

Inhibition of Hen Brain Acetylcholinesterase and Neurotoxic Esterase by Chlorpyrifos in Vivo and Kinetics of Inhibition by Chlorpyrifos Oxon in Vitro: Application to Assessment of Neuropathic Risk

Inhibition of Hen Brain Acetylcholinesterase and Neurotoxic Esterase by Chlorpyrifos in Vivo and Kinetics of Inhibition by Chlorpyrifos Oxon in Vitro : Application to Assessment of Neuropathic Risk. Richardson, R. J., Moore, T. B., Kayyali, U. S., Fowke, J. H., and Randall, J. C. (1993). Fundam. Appl. Toxicol. 20, 273-279.Chlorpyrifos (CPS; O,O-diethyl 3,5,6-trichloro-2-pyridyl phosphorothionate; Dursban) is a widely used broad-spectrum organophosphorus (OP) insecticide. Because some OP compounds can cause a sensory-motor distal axonopathy called OP compound-induced delayed neurotoxicity (OPIDN), CPS has been evaluated for this paralytic effect. Early studies of the neurotoxicity of CPS in young and adult hens reported reversible leg weakness but failed to detect OPIDN. More recently, a human case of mild OPIDN was reported to result from ingestion of a massive dose (about 300 mg/kg) in a suicide attempt. Subsequent experiments in adult hens (the currently accepted animal model of choice for studies of OPIDN) showed that doses of CPS in excess of the LD50 in atropine-treated animals inhibited brain neurotoxic esterase (NTE) and produced mild to moderate ataxia. Considering the extensive use of CPS and its demonstrated potential for causing OPIDN at supralethal doses, additional data are needed to enable quantitative estimates to be made of the neuropathic risk of this compound. Previous work has shown that the ability of OP insecticides to cause acute cholinergic toxicity versus OPIDN can be predicted from their relative tendency to inhibit the intended target, acetylcholinesterase (ACHE), versus the putative neuropathic target, NTE, in brain tissue. The present study was designed to clarify the magnitude of neuropathic risk associated with CPS exposures by measuring hen brain AChE and NTE inhibition following dosing in vivo and determining the bimolecular rate constant of inhibition (ki) for each enzyme by the active metabolite, CPS oxon (CPO), in vitro. CPS administered to atropine-treated adult hens at 0, 75, 150, and 300 mg/kg po in corn oil produced mean values for brain AChE inhibition 4 days after dosing of 0, 58, 75, and 86%, respectively, and mean values for brain NTE inhibition of 0, 21, 40, and 77%, respectively. Only the high dose (six times the unprotected LD50 in hens) produced NTE inhibition above the presumed threshold of 70%, and these animals were in extremis from cholinergic toxicity at the time of euthanization despite continual treatment with atropine. When 150 mg/kg CPS po in corn oil was given to atropine-treated hens on Day 0, inhibition on Days 1, 2, 4, 8, and 16 for brain AChE was 86, 82, 72, 44, and 29%, respectively, and for brain NTE was 30, 28, 38, 29, and 6%, respectively. No signs of OPIDN were observed in any of the animals during the 16-day study period. Kinetic studies of the inhibition of hen brain AChE and NTE by CPO in vitro demonstrated that CPO exhibits high potency and extraordinary selectivity for its intended target, ACHE. The ki values were 15.5 [mu]M-1 min-1 for AChE and 0.145 [mu]M-1 min-1 for NTE. The calculated fixed-time (20-min) I50 values were 2.24 nM for AChE and 239 nM for NTE, yielding an I50 ratio for NTE/AChE of 107. These results may be compared with data compiled for other OP compounds with respect to NTE/AChE I50 ratios and the corresponding doses required to produce OPIDN relative to the LD50. In general, NTE/AChE I50 ratios greater than 1 indicate that the dose required to produce OPIDN is greater than the LD50. Taken together, the results of this study indicate that acute exposures to CPS would not be expected to cause OPIDN except under extreme conditions such as attempted suicides involving medically assisted survival of doses considerably in excess of the LD50.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30877/1/0000541.pd

Transforming Growth Factor-β1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src

Transforming growth factor (TGF)-β1 activity has been shown to increase vascular endothelial barrier permeability, which is believed to precede several pathologic conditions, including pulmonary edema and vessel inflammation. In endothelial monolayers, TGF-β1 increases permeability, and a number of studies have demonstrated the alteration of cell–cell contacts by TGF-β1. We hypothesized that focal adhesion complexes also likely contribute to alterations in endothelial permeability. We examined early signal transduction events associated with rapid changes in monolayer permeability and the focal adhesion complex of bovine pulmonary artery endothelial cells. Western blotting revealed rapid tyrosine phosphorylation of focal adhesion kinase (FAK) and Src kinase in response to TGF-β1; inhibition of both of these kinases using pp2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), ameliorates TGF-β1–induced monolayer permeability. Activation of FAK/Src requires activation of the epidermal growth factor receptor downstream of the TGF-β receptors, and is blocked by the epidermal growth factor receptor inhibitor AG1478. Immunohistochemistry showed that actin and the focal adhesion proteins paxillin, vinculin, and hydrogen peroxide–inducible clone-5 (Hic-5) are rearranged in response to TGF-β1; these proteins are released from focal adhesion complexes. Rearrangement of paxillin and vinculin by TGF-β1 is not blocked by the FAK/Src inhibitor, pp2, or by SB431542 inhibition of the TGF-β type I receptor, anaplastic lymphoma kinase 5; however, pp1 (4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), which inhibits both type I and type II TGF-β receptors, does block paxillin and vinculin rearrangement. Hic-5 protein rearrangement requires FAK/Src activity. Together, these results suggest that TGF-β1–induced monolayer permeability involves focal adhesion and cytoskeletal rearrangement through both FAK/Src-dependent and -independent pathways