172 research outputs found
Self-reflection, rehabilitation and returning to fitness: an interpretative phenomenological analysis of stroke survivors’ experiences
Each year, over 100,000 individuals suffer strokes in the United Kingdom alone, and it is estimated that by 2035, not only will there be a 59% increase in the number of first-time strokes amongst individuals of 45 years and over, but also that there will be a significant increase in the proportion of survivors thereby requiring effective rehabilitation (Sentinel Stroke National Audit Programme (SSNAP)). Contemporary research has indicated, however, that many of the rehabilitation schemes currently provided can be somewhat variable in approach, and often focus strongly upon regaining physiological function at the expense of assisting patients with the more psychological and social elements essential to their recovery. Indeed, stroke survivors have reported particular dissatisfaction with their rehabilitation in terms of a lack of help with stress-management and access to social support mechanisms. There is, thus, further research needed into the complex experiences of individuals who have undergone stroke rehabilitation in order to better understand their nuanced needs, and how these were met (or not met) by the services provided. Therefore, this study aimed to explore extended, semi-structured interviews, reflecting on personal experiences of stroke and subsequent rehabilitation, with the purpose of drawing conclusions to potentially form a basis for further research. The reported study used Interpretative Phenomenological Analysis (IPA) to explore interviews with n=4 individuals (2 males and 2 females) who have (a) experienced a stroke in the last five years, and have (b) now fully completed their formal rehabilitation programmes, i.e. are no longer under regular NHS care. These participants are, thus, in an ideal position to provide a full account of, and reflection upon, their journey through the rehabilitation process. All interviews were conducted and recorded via telephone, while all collected data were handled in strict accordance with the institutional ethical conditions set-out for the project, stored in line with General Data Protection regulation (GDPR), and analysed using the standard conventions of IPA. Although analysis remains in progress at this time, it is currently clear that, for the participants, the rehabilitative experience was influenced by the manner in which they conceptualized their pre-stroke identities. Perceived difficulties within the process were most notable where participants felt that they were not being identified as an individual. Given such observations, it is contended that the results and subsequent conclusions made could potentially influence further research into the structure and delivery of stroke rehabilitation
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Metallothionein-I/II expression associates with the astrocyte DNA damage response and not Alzheimer-type pathology in the ageing brain
Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer’s disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and –II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS)
aging population-representative neuropathology cohort, and examined H2O2-modulation of MT transcription by human astrocytes. MT-I/II is primarily expressed by astrocytes in the aging brain, but is also associated with pyramidal neurons in a small proportion of cases. Astrocyte expression of MT-I/II does not correlate with Alzheimer-type pathology (Aβ plaques and neurofibrillary tangles) but does relate to astrocyte oxidative DNA damage (rs= 0.312, p= 0.006) and the astrocyte response to oxidative DNA damage in vivo (rs= 0.238, p= 0.04), and MT gene expression is significantly induced in human astrocytes response to oxidative stress in vitro (p=0.01). In contrast, neuronal MT-I/II does not relate to oxidative DNA damage or the neuronal DNA damage response, but is significantly higher in cases with high levels of local tangle pathology (p=0.007). As MT-I/II is neuroprotective against
oxidative stress, modulation of MT-I/II expression is a potential therapeutic target to treat the onset and progression of cognitive impairment
Almost a spider: a 305-million-year-old fossil arachnid and spider origins
Spiders are an important animal group, with a long history. Details of their origins remain limited, with little knowledge of their stem group, and no insights into the sequence of character acquisition during spider evolution. We describe a new fossil arachnid, Idmonarachne brasieri gen. et sp. nov. from the Late Carboniferous (Stephanian, ca 305–299 Ma) of Montceau-les-Mines, France. It is three-dimensionally preserved within a siderite concretion, allowing both laboratory- and synchrotron-based phase-contrast computed tomography reconstruction. The latter is a first for siderite-hosted fossils and has allowed us to investigate fine anatomical details. Although distinctly spider-like in habitus, this remarkable fossil lacks a key diagnostic character of Araneae: spinnerets on the underside of the opisthosoma. It also lacks a flagelliform telson found in the recently recognized, spider-related, Devonian–Permian Uraraneida. Cladistic analysis resolves our new fossil as sister group to the spiders: the spider stem-group comprises the uraraneids and I. brasieri. While we are unable to demonstrate the presence of spigots in this fossil, the recovered phylogeny suggests the earliest character to evolve on the spider stem-group is the secretion of silk. This would have been followed by the loss of a flagelliform telson, and then the ability to spin silk using spinnerets. This last innovation defines the true spiders, significantly post-dates the origins of silk, and may be a key to the group's success. The Montceau-les-Mines locality has previously yielded a mesothele spider (with spinnerets). Evidently, Late Palaeozoic spiders lived alongside Palaeozoic arachnid grades which approached the spider condition, but did not express the full suite of crown-group autapomorphies
NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology in the Ageing Brain.
Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer's disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response
Sedimentary DNA from a submerged site reveals wheat in the British Isles 8000 years ago
YesThe Mesolithic-to-Neolithic transition marked the time when a hunter-gatherer economy gave way to agriculture, coinciding with rising sea levels. Bouldnor Cliff, is a submarine archaeological site off the Isle of Wight in the United Kingdom that has a well-preserved Mesolithic paleosol dated to 8000 years before the present. We analyzed a core obtained from sealed sediments, combining evidence from microgeomorphology and microfossils with sedimentary ancient DNA (sedaDNA) analyses to reconstruct floral and faunal changes during the occupation of this site, before it was submerged. In agreement with palynological analyses, the sedaDNA sequences suggest a mixed habitat of oak forest and herbaceous plants. However, they also provide evidence of wheat 2000 years earlier than mainland Britain and 400 years earlier than proximate European sites. These results suggest that sophisticated social networks linked the Neolithic front in southern Europe to the Mesolithic peoples of northern Europe
Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.
AIMS: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS: Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis. RESULTS: Two thousand three hundred seventy-eight genes were significantly differentially expressed (1690 up-regulated, 688 down-regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up-regulation of glycogen synthase kinase 3β. Candidate genes were validated by quantitative real-time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)-hydroxycholesterol associated with neuronal DDR across all Braak stages (rs = 0.30, P = 0.03). CONCLUSIONS: A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3β, thereby contributing to neuronal dysfunction independent of Alzheimer-type pathology in the ageing brain
Seed polyphenols in a diverse tropical plant community
1.Polyphenols are one of the most common groups of secondary metabolites in plants and thought to play a key role in enhancing plant fitness by protecting plants against enemies. Although enemy‐inflicted mortality at the seed stage can be an important regulator of plant populations and a key determinant of community structure, few studies have assessed community‐level patterns of polyphenol content in seeds. 2.We describe the distribution of the main seed polyphenol groups across 196 tree and liana species on Barro Colorado Island (Panama) and community‐level patterns in two aspects of their biological activity (protein precipitation and oxidative capacity). Taking advantage of substantial variation in morphological and ecological traits in the studied plant community, we test for correlations and trade‐offs between seed polyphenols and nonchemical plant traits hypothesised to make plant species more or less likely to invest in polyphenol production. 3.The majority of species have polyphenols in their seeds. The incidence and concentrations of polyphenols were related to a set of nonchemical plant traits. Polyphenols were most likely to be present (and where present, to be expressed in high concentrations) in species with large seeds, short seed dormancy times, low investment in mechanical seed defences, high wood density, high leaf mass per area, tough leaves and slow growth rates. 4.Synthesis. Our study reveals a potential trade‐off between chemical and mechanical seed defences and shows that plant species that invest in physical defences at later life stages (high wood density and tough leaves) tend not to invest in physical defences of seeds but instead produce secondary metabolites likely to act as seed defences. Overall, our results conform to predictions from the resource availability hypothesis, which states that species in resource‐limited environments (such as slow‐growing shade‐tolerant tree species) will invest more in defences than fast‐growing pioneer species. </p
Ethical, Legal, and Policy Challenges in Field-Based Neuroimaging Research Using Emerging Portable MRI Technologies: Guidance for Investigators and for Oversight
Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG’s consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control
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