| 41. |
- Deshpande, J, et al.
(författare)
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Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death.
- 1992
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Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - 0014-4819. ; 88:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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| 42. |
- Zhu, Changlian, 1964, et al.
(författare)
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X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants.
- 2007
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Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 26:12, s. 3402-10
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that X chromosome-linked inhibitor of apoptosis protein (XIAP) counteracts oxidative stress in two essentially different disease-related models of brain injury, hypoxia-ischemia and irradiation, as judged by lower expression of nitrotyrosine (5-fold) and 4-hydroxy-2-nonenal (10-fold) in XIAP-overexpressing compared with wild-type mice. XIAP overexpression induced up-regulation of at least three antioxidants residing in mitochondria, superoxide dismutase 2, thioredoxin 2 and lysine oxoglutarate reductase. Cytochrome c release from mitochondria was reduced in XIAP-overexpressing mice. Hence, in addition to blocking caspases, XIAP can regulate reactive oxygen species in the brain, at least partly through up-regulation of mitochondrial antioxidants. XIAP-induced prevention of oxidative stress was not secondary to tissue protection because although XIAP overexpression provides tissue protection after hypoxia-ischemia, it does not prevent tissue loss after irradiation. This is a previously unknown role of XIAP and may provide the basis for development of novel protective strategies for both acute and chronic neurodegenerative diseases, where oxidative stress is an integral component of the injury mechanisms involved.
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| 43. |
- Brayne, C. E., et al.
(författare)
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Dementia Research Fit for the Planet: Reflections on Population Studies of Dementia for Researchers and Policy Makers Alike
- 2020
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 54:2, s. 157-170
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past.
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| 44. |
- Lawrence, Maggie, et al.
(författare)
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Stroke secondary prevention, a non-surgical and non-pharmacological consensus definition: results of a Delphi study
- 2019
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Evidence supporting lifestyle modification in vascular risk reduction is limited, drawn largely from primary prevention studies. To advance the evidence base for non-pharmacological and non-surgical stroke secondary prevention (SSP), empirical research is needed, informed by a consensus-derived definition of SSP. To date, no such definition has been published. We used Delphi methods to generate an evidence-based definition of non-pharmacological and non-surgical SSP. RESULTS: The 16 participants were members of INSsPiRE (International Network of Stroke Secondary Prevention Researchers), a multidisciplinary group of trialists, academics and clinicians. The Elicitation stage identified 49 key elements, grouped into 3 overarching domains: Risk factors, Education, and Theory before being subjected to iterative stages of elicitation, ranking, discussion, and anonymous voting. In the Action stage, following an experience-based engagement with key stakeholders, a consensus-derived definition, complementing current pharmacological and surgical SSP pathways, was finalised: Non-pharmacological and non-surgical stroke secondary prevention supports and improves long-term health and well-being in everyday life and reduces the risk of another stroke, by drawing from a spectrum of theoretically informed interventions and educational strategies. Interventions to self-manage modifiable lifestyle risk factors are contextualized and individualized to the capacities, needs, and personally meaningful priorities of individuals with stroke and their families.
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| 45. |
- Simistira Liwicki, Foteini, et al.
(författare)
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Bimodal electroencephalography-functional magnetic resonance imaging dataset for inner-speech recognition
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The recognition of inner speech, which could give a ‘voice’ to patients that have no ability to speak or move, is a challenge for brain-computer interfaces (BCIs). A shortcoming of the available datasets is that they do not combine modalities to increase the performance of inner speech recognition. Multimodal datasets of brain data enable the fusion of neuroimaging modalities with complimentary properties, such as the high spatial resolution of functional magnetic resonance imaging (fMRI) and the temporal resolution of electroencephalography (EEG), and therefore are promising for decoding inner speech. This paper presents the first publicly available bimodal dataset containing EEG and fMRI data acquired nonsimultaneously during inner-speech production. Data were obtained from four healthy, right-handed participants during an inner-speech task with words in either a social or numerical category. Each of the 8-word stimuli were assessed with 40 trials, resulting in 320 trials in each modality for each participant. The aim of this work is to provide a publicly available bimodal dataset on inner speech, contributing towards speech prostheses.
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| 46. |
- Thorgeirsson, T. E., et al.
(författare)
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A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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| 47. |
- Palmqvist, Sebastian, et al.
(författare)
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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
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| 48. |
- Tseli, Elena, et al.
(författare)
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Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain : protocol for a systematic review and meta-analysis
- 2017
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Ingår i: Systematic Reviews. - : BioMed Central (BMC). - 2046-4053. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Chronic musculoskeletal pain is a major public health problem. Early prediction for optimal treatment results has received growing attention, but there is presently a lack of evidence regarding what information such proactive management should be based on. This study protocol, therefore, presents our planned systematic review and meta-analysis on important predictive factors for health and work-related outcomes following multidisciplinary rehabilitation (MDR) in patients with chronic musculoskeletal pain.METHODS: We aim to perform a synthesis of the available evidence together with a meta-analysis of published peer-reviewed original research that includes predictive factors preceding MDR. Included are prospective studies of adults with benign, chronic (> 3 months) musculoskeletal pain diagnoses who have taken part in MDR. In the studies, associations between personal and rehabilitation-based factors and the outcomes of interest are reported. Outcome domains are pain, physical functioning including health-related quality of life, and work ability with follow-ups of 6 months or more. We will use a broad, explorative approach to any presented predictive factors (demographic, symptoms-related, physical, psychosocial, work-related, and MDR-related) and these will be analyzed through (a) narrative synthesis for each outcome domain and (b) if sufficient studies are available, a quantitative synthesis in which variance-weighted pooled proportions will be computed using a random effects model for each outcome domain. The strength of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation.DISCUSSION: The strength of this systematic review is that it aims for a meta-analysis of prospective cohort or randomized controlled studies by performing an extensive search of multiple databases, using an explorative study approach to predictive factors, rather than building on single predictor impact on the outcome or on predefined hypotheses. In this way, an overview of factors central to MDR outcome can be made and will help strengthen the evidence base and inform a wide readership including health care practitioners and policymakers.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016025339.
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| 49. |
- Ozanne, Anneli, 1978, et al.
(författare)
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Symptom relief during last week of life in neurological diseases
- 2019
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to investigate symptom prevalence, symptom relief, and palliative care indicators during the last week of life, comparing them for patients with motor neuron disease (MND), central nervous system tumors (CNS tumor), and other neurological diseases (OND). Material & Methods Data were obtained from the Swedish Register for Palliative Care, which documents care during the last week of life. Logistic regression was used to compare patients with MND (n = 419), CNS tumor (n = 799), and OND (n = 1,407) as the cause of death. Results The most prevalent symptoms for all neurological disease groups were pain (52.7% to 72.2%) and rattles (58.1% to 65.6%). Compared to MND and OND, patients with CNS tumors were more likely to have totally relieved pain, shortness of breath, rattles, and anxiety. They were also more likely to have their pain assessed with a validated tool; to receive symptom treatment for anxiety, nausea, rattles, and pain; to have had family members receive end-of-life discussions; to have someone present at death; and to have had their family members offered bereavement support. Both patients with CNS tumor and MND were more likely than patients with OND to receive consultation with a pain unit and to have had end-of-life discussions. Conclusions The study reveals high symptom burden and differences in palliative care between the groups during the last week of life. There is a need for person-centered care planning based on a palliative approach, focused on improving symptom assessments, relief, and end-of-life conversations.
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| 50. |
- Rajda, Cecilia, et al.
(författare)
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Increased dopamine content in lymphocytes from high-dose L-Dopa-treated Parkinson's disease patients
- 2005
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Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1021-7401 .- 1423-0216. ; 12:2, s. 81-84:12, s. 81-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The intracellular (i.c.) content of dopamine and its metabolites was measured in the peripheral blood lymphocytes (PBLs) of Parkinson's disease (PD) patients and healthy controls. METHODS: Catecholamine levels of PBLs were measured using capillary electrophoresis in healthy controls and PD patients receiving different doses of L-dihydroxyphenylalanine (L-Dopa). RESULTS: Higher i.c. dopamine content was found in lymphocytes from PD patients receiving a high dose of L-Dopa (700 +/- 30 mg/day) as compared to lymphocytes from the healthy controls (p = 0.002) and from PD patients treated with a low dose of L-Dopa (400 +/- 30 mg/day) (p = 0.022). The dihydroxyphenylacetic acid to dopamine ratio was significantly lower in the high-dose L-Dopa-treated PD patients than in the controls (p = 0.013). CONCLUSIONS: These findings suggest that the dopamine content and metabolism in the peripheral lymphocytes of PD patients are influenced by L-Dopa administration. This is the first study in which a dose-related effect of L-Dopa treatment was found in lymphocytes from PD patients.
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