Pub Date : 2019-05-21DOI: 10.12688/AMRCOPENRES.12873.2
S. Northcott, A. Simpson, Shirley A. Thomas, S. Hirani, C. Flood, K. Hilari
Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.
{"title":"Solution Focused brief therapy In post-stroke Aphasia (SOFIA Trial): protocol for a feasibility randomised controlled trial","authors":"S. Northcott, A. Simpson, Shirley A. Thomas, S. Hirani, C. Flood, K. Hilari","doi":"10.12688/AMRCOPENRES.12873.2","DOIUrl":"https://doi.org/10.12688/AMRCOPENRES.12873.2","url":null,"abstract":"Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.","PeriodicalId":72183,"journal":{"name":"AMRC open research","volume":"389 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41280824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-15DOI: 10.12688/amrcopenres.12875.1
I. Rajkovic, Raymond Wong, Eloise Lemarchand, R. Tinker, S. Allan, E. Pinteaux
Introduction: The acute phase protein pentraxin 3 (PTX3) is known for its anti-inflammatory effects through downregulating neutrophil transmigration during peripheral inflammation. Furthermore, we have previously demonstrated a neuroprotective and neuroreparative effect of PTX3 after cerebral ischaemia. Here we investigated, to our knowledge for the first time, the role of PTX3 in neutrophil transmigration and neurotoxicity following lipopolysaccharide (LPS)-induced cerebral inflammation and cerebral ischaemia. Methods: Neutrophil transmigration through interleukin-1β (IL-1β) activated brain endothelium and neurotoxicity of neutrophils isolated from wild-type (WT) or PTX3 knock-out (KO) mice was assessed in vitro. Primary cortical neuronal death after treatment with transmigrated neutrophils was quantified by lactate dehydrogenase (LDH) assay. Cerebral inflammation or ischemia was induced in WT and PTX3 KO mice via intrastriatal LPS injection or by transient middle cerebral artery occlusion (MCAo) respectively. Subsequent neutrophil infiltration in the brain was assessed by immunohistochemistry and the expression of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1β by enzyme-linked immunosorbent assay (ELISA). Results: Neutrophils isolated from WT mice after intrastriatal LPS injection transmigrated significantly more through IL-1β activated brain endothelium compared to neutrophils from PTX3 KO mice. Transmigrated WT and PTX3 KO neutrophils were significantly more neurotoxic than corresponding non-transmigrated neutrophils; however, no significant differences in neurotoxicity between genotypes were observed. PTX3 reduced the number of transmigrated neutrophils to the brain after intrastriatal LPS injection. Furthermore, PTX3 KO mice showed significantly increased levels of neutrophils in the brain after LPS administration or in the ischaemic hemisphere after MCAo, compared to WT mice. Conclusion: Our study shows that PTX3 regulates neutrophil transmigration in the CNS during neuroinflammation, demonstrating the potential of PTX3 as an effective therapeutic target in neuroinflammatory conditions.
{"title":"Pentraxin 3 regulates neutrophil infiltration to the brain during neuroinflammation","authors":"I. Rajkovic, Raymond Wong, Eloise Lemarchand, R. Tinker, S. Allan, E. Pinteaux","doi":"10.12688/amrcopenres.12875.1","DOIUrl":"https://doi.org/10.12688/amrcopenres.12875.1","url":null,"abstract":"Introduction: The acute phase protein pentraxin 3 (PTX3) is known for its anti-inflammatory effects through downregulating neutrophil transmigration during peripheral inflammation. Furthermore, we have previously demonstrated a neuroprotective and neuroreparative effect of PTX3 after cerebral ischaemia. Here we investigated, to our knowledge for the first time, the role of PTX3 in neutrophil transmigration and neurotoxicity following lipopolysaccharide (LPS)-induced cerebral inflammation and cerebral ischaemia. Methods: Neutrophil transmigration through interleukin-1β (IL-1β) activated brain endothelium and neurotoxicity of neutrophils isolated from wild-type (WT) or PTX3 knock-out (KO) mice was assessed in vitro. Primary cortical neuronal death after treatment with transmigrated neutrophils was quantified by lactate dehydrogenase (LDH) assay. Cerebral inflammation or ischemia was induced in WT and PTX3 KO mice via intrastriatal LPS injection or by transient middle cerebral artery occlusion (MCAo) respectively. Subsequent neutrophil infiltration in the brain was assessed by immunohistochemistry and the expression of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1β by enzyme-linked immunosorbent assay (ELISA). Results: Neutrophils isolated from WT mice after intrastriatal LPS injection transmigrated significantly more through IL-1β activated brain endothelium compared to neutrophils from PTX3 KO mice. Transmigrated WT and PTX3 KO neutrophils were significantly more neurotoxic than corresponding non-transmigrated neutrophils; however, no significant differences in neurotoxicity between genotypes were observed. PTX3 reduced the number of transmigrated neutrophils to the brain after intrastriatal LPS injection. Furthermore, PTX3 KO mice showed significantly increased levels of neutrophils in the brain after LPS administration or in the ischaemic hemisphere after MCAo, compared to WT mice. Conclusion: Our study shows that PTX3 regulates neutrophil transmigration in the CNS during neuroinflammation, demonstrating the potential of PTX3 as an effective therapeutic target in neuroinflammatory conditions.","PeriodicalId":72183,"journal":{"name":"AMRC open research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45212456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-19DOI: 10.12688/AMRCOPENRES.12861.1
Kelly Hares, S. Miners, N. Scolding, S. Love, A. Wilkins
Background: Early disturbances in axonal transport, before the onset of gross neuropathology, occur in a spectrum of neurodegenerative diseases including Alzheimer’s disease. Kinesin superfamily motor proteins (KIFs) are responsible for anterograde protein transport within the axon of various cellular cargoes, including synaptic and structural proteins. Dysregulated KIF expression has been associated with AD pathology and genetic polymorphisms within kinesin-light chain-1 (KLC1) have been linked to AD susceptibility. We examined the expression of KLC1 in AD, in relation to that of the KLC1 motor complex (KIF5A) and to susceptibility genotypes. Methods: We analysed KLC1 and KIF5A gene and protein expression in midfrontal cortex from 47 AD and 39 control brains. Results: We found that gene expression of both KIF5A and KLC1 increased with Braak tangle stage (0-II vs III-IV and V-VI) but was not associated with significant change at the protein level. We found no effect of KLC1 SNPs on KIF5A or KLC1 expression but KIF5A SNPs that had previously been linked to susceptibility in multiple sclerosis were associated with reduced KIF5A mRNA expression in AD cortex. Conclusions: Future in vitro and in vivo studies are required to understand the cause of upregulated KIF5A and KLC-1 gene expression in AD and any potential downstream consequences on pathogenesis, including any contribution of genetic polymorphisms within the KIF5A gene locus.
背景:轴突运输的早期紊乱，在总体神经病理学发病之前，发生在包括阿尔茨海默病在内的一系列神经退行性疾病中。运动蛋白超家族运动蛋白(KIFs)负责各种细胞货物轴突内的蛋白质顺行运输，包括突触和结构蛋白。失调的KIF表达与阿尔茨海默病病理有关，而激酶-轻链-1 (KLC1)内的遗传多态性与阿尔茨海默病易感性有关。我们检测了KLC1在AD中的表达，以及KLC1运动复合物(KIF5A)和易感基因型的表达。方法:对47例AD患者和39例对照患者中额叶皮层KLC1和KIF5A基因及蛋白表达进行分析。结果:我们发现KIF5A和KLC1的基因表达随着Braak缠结期(0-II vs III-IV和V-VI)的增加而增加，但在蛋白水平上没有显著变化。我们没有发现KLC1 snp对KIF5A或KLC1表达的影响，但先前与多发性硬化症易感性相关的KIF5A snp与AD皮质中KIF5A mRNA表达减少有关。结论:需要进一步的体外和体内研究来了解AD中KIF5A和KLC-1基因表达上调的原因，以及对发病机制的任何潜在下游影响，包括KIF5A基因位点内遗传多态性的任何贡献。
{"title":"KIF5A and KLC1 expression in Alzheimer’s disease: relationship and genetic influences","authors":"Kelly Hares, S. Miners, N. Scolding, S. Love, A. Wilkins","doi":"10.12688/AMRCOPENRES.12861.1","DOIUrl":"https://doi.org/10.12688/AMRCOPENRES.12861.1","url":null,"abstract":"Background: Early disturbances in axonal transport, before the onset of gross neuropathology, occur in a spectrum of neurodegenerative diseases including Alzheimer’s disease. Kinesin superfamily motor proteins (KIFs) are responsible for anterograde protein transport within the axon of various cellular cargoes, including synaptic and structural proteins. Dysregulated KIF expression has been associated with AD pathology and genetic polymorphisms within kinesin-light chain-1 (KLC1) have been linked to AD susceptibility. We examined the expression of KLC1 in AD, in relation to that of the KLC1 motor complex (KIF5A) and to susceptibility genotypes. Methods: We analysed KLC1 and KIF5A gene and protein expression in midfrontal cortex from 47 AD and 39 control brains. Results: We found that gene expression of both KIF5A and KLC1 increased with Braak tangle stage (0-II vs III-IV and V-VI) but was not associated with significant change at the protein level. We found no effect of KLC1 SNPs on KIF5A or KLC1 expression but KIF5A SNPs that had previously been linked to susceptibility in multiple sclerosis were associated with reduced KIF5A mRNA expression in AD cortex. Conclusions: Future in vitro and in vivo studies are required to understand the cause of upregulated KIF5A and KLC-1 gene expression in AD and any potential downstream consequences on pathogenesis, including any contribution of genetic polymorphisms within the KIF5A gene locus.","PeriodicalId":72183,"journal":{"name":"AMRC open research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43782795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-19DOI: 10.12688/AMRCOPENRES.12862.2
B. Drozdowska, C. Celis-Morales, D. Lyall, T. Quinn
Background: Findings from studies in older adult populations suggest that measures of social engagement may be associated with health outcomes, including cognitive function. Plausibly the magnitude and direction of this association may differ in stroke. The disabling nature of stroke increases the likelihood of social isolation and stroke survivors are at high risk of cognitive decline. We assessed the association between social engagement and cognitive function in a sample of stroke survivors. Methods: We included available data from stroke survivors in the UK Biobank (N=8776; age range: 40-72; 57.4% male). In a series of regression models, we assessed cross-sectional associations between proxies of social engagement (frequency of family/friend visits, satisfaction with relationships, loneliness, opportunities to confide in someone, participation in social activities) and performance on domain specific cognitive tasks: reaction time, verbal-numerical reasoning, visual memory and prospective memory. We adjusted for demographics, health-, lifestyle-, and stroke-related factors. Accounting for multiple testing, we set our significance threshold at p<0.003. Results: After adjusting for covariates, we found independent associations between faster reaction times and monthly family visits as compared to no visit (standardised beta=-0.32, 99.7% CI: -0.61 to -0.03, N=4,930); slower reaction times and religious group participation (standardised beta=0.25, 99.7% CI 0.07 to 0.44, N=4,938); and poorer performance on both verbal-numerical reasoning and prospective memory tasks with loneliness (standardised beta=-0.19, 99.7% CI: -0.34 to -0.03, N=2,074; odds ratio=0.66, 99.7% CI: 0.46 to 0.94, N=2,188; respectively). In models where all proxies of social engagement were combined, no associations remained significant. Conclusions: We found limited task-specific associations between cognitive performance and proxies of social engagement, with only loneliness related to two tasks. Further studies are necessary to confirm and improve our understanding of these relationships and investigate the potential to target psychosocial factors to support cognitive function in stroke survivors.
{"title":"Social engagement after stroke – is it relevant to cognitive function? A cross-sectional analysis of UK Biobank data","authors":"B. Drozdowska, C. Celis-Morales, D. Lyall, T. Quinn","doi":"10.12688/AMRCOPENRES.12862.2","DOIUrl":"https://doi.org/10.12688/AMRCOPENRES.12862.2","url":null,"abstract":"Background: Findings from studies in older adult populations suggest that measures of social engagement may be associated with health outcomes, including cognitive function. Plausibly the magnitude and direction of this association may differ in stroke. The disabling nature of stroke increases the likelihood of social isolation and stroke survivors are at high risk of cognitive decline. We assessed the association between social engagement and cognitive function in a sample of stroke survivors. Methods: We included available data from stroke survivors in the UK Biobank (N=8776; age range: 40-72; 57.4% male). In a series of regression models, we assessed cross-sectional associations between proxies of social engagement (frequency of family/friend visits, satisfaction with relationships, loneliness, opportunities to confide in someone, participation in social activities) and performance on domain specific cognitive tasks: reaction time, verbal-numerical reasoning, visual memory and prospective memory. We adjusted for demographics, health-, lifestyle-, and stroke-related factors. Accounting for multiple testing, we set our significance threshold at p<0.003. Results: After adjusting for covariates, we found independent associations between faster reaction times and monthly family visits as compared to no visit (standardised beta=-0.32, 99.7% CI: -0.61 to -0.03, N=4,930); slower reaction times and religious group participation (standardised beta=0.25, 99.7% CI 0.07 to 0.44, N=4,938); and poorer performance on both verbal-numerical reasoning and prospective memory tasks with loneliness (standardised beta=-0.19, 99.7% CI: -0.34 to -0.03, N=2,074; odds ratio=0.66, 99.7% CI: 0.46 to 0.94, N=2,188; respectively). In models where all proxies of social engagement were combined, no associations remained significant. Conclusions: We found limited task-specific associations between cognitive performance and proxies of social engagement, with only loneliness related to two tasks. Further studies are necessary to confirm and improve our understanding of these relationships and investigate the potential to target psychosocial factors to support cognitive function in stroke survivors.","PeriodicalId":72183,"journal":{"name":"AMRC open research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46981718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-19DOI: 10.12688/AMRCOPENRES.12855.1
K. Flemming, K. Atkin, C. Ward, I. Watt
Background: There is an increasing emphasis on the importance of the palliative and end-of-life care being provided in the community. Key to the success of this is the availability of information and educational support to facilitate carers in their role. The aim of the paper is to explore the educational needs of adult carers providing physical and other care to people at the end of life Methods: A qualitative evidence synthesis was conducted using meta-ethnography. Five electronic databases were searched to January 2014, combining terms for: cancer, chronic obstructive pulmonary disease, neurodegenerative conditions, renal disease, heart failure and dementia, with terms for carers and education. Results: A total of 35 papers were included in the review, reporting the experiences of over 900 carers. Throughout the illness trajectory carers were either enabled or hindered in their role by the nature and way information and education were provided. Enabling factors included: a sense of trust in health professionals; timely and accurate information delivered compassionately; access to professionals for information and support particularly during out-of-hours. Where carers experienced a lack of information or support this added to the strain of caring. Carers then felt the need to take on a more active role, acting both as an advocate and decision maker. Conclusions: Carers express information and educational needs throughout the illness trajectory. The quality of health professionals’ communication with carers was fundamental in ensuring carers felt confident and supported. Timely access to information and support from appropriately qualified health professionals should be made available to carers, including the out-of-hours period.
{"title":"Adult family carers’ perceptions of their educational needs when providing end-of-life care: a systematic review of qualitative research","authors":"K. Flemming, K. Atkin, C. Ward, I. Watt","doi":"10.12688/AMRCOPENRES.12855.1","DOIUrl":"https://doi.org/10.12688/AMRCOPENRES.12855.1","url":null,"abstract":"Background: There is an increasing emphasis on the importance of the palliative and end-of-life care being provided in the community. Key to the success of this is the availability of information and educational support to facilitate carers in their role. The aim of the paper is to explore the educational needs of adult carers providing physical and other care to people at the end of life Methods: A qualitative evidence synthesis was conducted using meta-ethnography. Five electronic databases were searched to January 2014, combining terms for: cancer, chronic obstructive pulmonary disease, neurodegenerative conditions, renal disease, heart failure and dementia, with terms for carers and education. Results: A total of 35 papers were included in the review, reporting the experiences of over 900 carers. Throughout the illness trajectory carers were either enabled or hindered in their role by the nature and way information and education were provided. Enabling factors included: a sense of trust in health professionals; timely and accurate information delivered compassionately; access to professionals for information and support particularly during out-of-hours. Where carers experienced a lack of information or support this added to the strain of caring. Carers then felt the need to take on a more active role, acting both as an advocate and decision maker. Conclusions: Carers express information and educational needs throughout the illness trajectory. The quality of health professionals’ communication with carers was fundamental in ensuring carers felt confident and supported. Timely access to information and support from appropriately qualified health professionals should be made available to carers, including the out-of-hours period.","PeriodicalId":72183,"journal":{"name":"AMRC open research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44477456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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