RESUMO
Human society is dependent on nature1,2, but whether our ecological foundations are at risk remains unknown in the absence of systematic monitoring of species' populations3. Knowledge of species fluctuations is particularly inadequate in the marine realm4. Here we assess the population trends of 1,057 common shallow reef species from multiple phyla at 1,636 sites around Australia over the past decade. Most populations decreased over this period, including many tropical fishes, temperate invertebrates (particularly echinoderms) and southwestern Australian macroalgae, whereas coral populations remained relatively stable. Population declines typically followed heatwave years, when local water temperatures were more than 0.5 °C above temperatures in 2008. Following heatwaves5,6, species abundances generally tended to decline near warm range edges, and increase near cool range edges. More than 30% of shallow invertebrate species in cool latitudes exhibited high extinction risk, with rapidly declining populations trapped by deep ocean barriers, preventing poleward retreat as temperatures rise. Greater conservation effort is needed to safeguard temperate marine ecosystems, which are disproportionately threatened and include species with deep evolutionary roots. Fundamental among such efforts, and broader societal needs to efficiently adapt to interacting anthropogenic and natural pressures, is greatly expanded monitoring of species' population trends7,8.
Assuntos
Antozoários , Recifes de Corais , Calor Extremo , Peixes , Aquecimento Global , Invertebrados , Oceanos e Mares , Água do Mar , Alga Marinha , Animais , Austrália , Peixes/classificação , Invertebrados/classificação , Aquecimento Global/estatística & dados numéricos , Alga Marinha/classificação , Dinâmica Populacional , Densidade Demográfica , Água do Mar/análise , Extinção Biológica , Conservação dos Recursos Naturais/tendências , Equinodermos/classificaçãoRESUMO
OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.
Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doenças Cardiovasculares , Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/epidemiologia , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/psicologia , Doença de Alzheimer/epidemiologiaRESUMO
INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/genética , Doenças de Pequenos Vasos Cerebrais/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.
Assuntos
Transtornos Cerebrovasculares , Demência Frontotemporal , Doenças Neurodegenerativas , Atividades Cotidianas , Cuidadores/psicologia , Humanos , OntárioRESUMO
Marine protected areas (MPAs) are a primary tool for the stewardship, conservation, and restoration of marine ecosystems, yet 69% of global MPAs are only partially protected (i.e., are open to some form of fishing). Although fully protected areas have well-documented outcomes, including increased fish diversity and biomass, the effectiveness of partially protected areas is contested. Partially protected areas may provide benefits in some contexts and may be warranted for social reasons, yet social outcomes often depend on MPAs achieving their ecological goals to distinguish them from open areas and justify the cost of protection. We assessed the social perceptions and ecological effectiveness of 18 partially protected areas and 19 fully protected areas compared with 19 open areas along 7000 km of coast of southern Australia. We used mixed methods, gathering data via semistructured interviews, site surveys, and Reef Life (underwater visual census) surveys. We analyzed qualitative data in accordance with grounded theory and quantitative data with multivariate and univariate linear mixed-effects models. We found no social or ecological benefits for partially protected areas relative to open areas in our study. Partially protected areas had no more fish, invertebrates, or algae than open areas; were poorly understood by coastal users; were not more attractive than open areas; and were not perceived to have better marine life than open areas. These findings provide an important counterpoint to some large-scale meta-analyses that conclude partially protected areas can be ecologically effective but that draw this conclusion based on narrower measures. We argue that partially protected areas act as red herrings in marine conservation because they create an illusion of protection and consume scarce conservation resources yet provide little or no social or ecological gain over open areas. Fully protected areas, by contrast, have more fish species and biomass and are well understood, supported, and valued by the public. They are perceived to have better marine life and be improving over time in keeping with actual ecological results. Conservation outcomes can be improved by upgrading partially protected areas to higher levels of protection including conversion to fully protected areas.
Análisis de la Efectividad Social y Ecológica de las Áreas Marinas Parcialmente Protegidas Resumen Las áreas marinas protegidas (AMPs) son una herramienta importante para la administración, conservación y restauración de los ecosistemas marinos; sin embargo, el 69% de las AMPs mundiales solamente están parcialmente protegidas (es decir, están abiertas a alguna forma de pesca). Aunque las áreas completamente protegidas tienen resultados bien documentados, incluyendo el incremento en la diversidad de peces y la biomasa, la efectividad de las áreas parcialmente protegidas está en disputa. Puede que las áreas parcialmente protegidas se justifiquen por razones sociales, aunque los resultados sociales con frecuencia dependen de que las AMPs alcancen sus metas ecológicas para distinguirlas de las áreas abiertas y justificar el costo de la protección. Analizamos las percepciones sociales y la efectividad ecológica de 18 áreas parcialmente protegidas y 19 áreas completamente protegidas a lo largo de 7000 km de costa en el sur de Australia. Usamos métodos mixtos, recopilando información por medio de entrevistas semiestructuradas, encuestas en sitio y censos Reef Life (censos visuales submarinos). Analizamos los datos cualitativos de acuerdo con la teoría fundamentada y los datos cuantitativos con modelos lineales de efectos mixtos multivariados y univariados. No encontramos beneficios sociales o ecológicos para las áreas parcialmente protegidas en relación con las áreas abiertas en nuestro estudio. Las áreas parcialmente protegidas no tuvieron más peces, invertebrados o algas que las áreas abiertas; los usuarios de la costa tenían poco entendimiento de ellas; no eran más atractivas que las áreas abiertas; y no eran percibidas como albergues de mejor vida marina que las áreas abiertas. Estos hallazgos proporcionan un contrapunto importante a algunos metaanálisis a gran escala que concluyen que las áreas parcialmente protegidas pueden ser ecológicamente efectivas, pero llegan a esta conclusión con base en medidas más reducidas. Discutimos que las áreas parcialmente protegidas funcionan como pistas falsas para la conservación marina pues crean una ilusión de estar protegidas y consumen pocos recursos para la conservación, pero proporcionan poca o ninguna ganancia ecológica o social en comparación con las áreas abiertas. Las áreas completamente protegidas, al contrario, tienen más especies de peces y biomasa y están bien comprendidas, respaldadas y valoradas por el público. Este tipo de AMPs son percibidas como albergues de mejor vida marina y como en constante mejora con el tiempo al mantenerse en regla con los resultados ecológicos actuales. Los resultados de la conservación pueden mejorarse si se eleva a las áreas parcialmente protegidas a niveles más altos de protección incluyendo la conversión a áreas completamente protegidas.
Assuntos
Ecossistema , Pesqueiros , Animais , Biomassa , Conservação dos Recursos Naturais , Peixes , Austrália do SulRESUMO
Rewilding is increasingly recognized as a conservation tool but is often context specific, which inhibits broad application. Rewilding in Australia seeks to enhance ecosystem function and promote self-sustaining ecosystems. An absence of large-bodied native herbivores means trophic rewilding in mainland Australia has focused on the restoration of functions provided by apex predators and small mammals. Because of the pervasive influence of introduced mesopredators, predator-proof fences, and establishment of populations on predator-free islands are common rewilding approaches. This sets Australian rewilding apart from most jurisdictions and provides globally relevant insights but presents challenges to restoring function to broader landscapes. Passive rewilding is of limited utility in arid zones. Although increasing habitat extent and quality in mesic coastal areas may work, it will likely be necessary to undertake active management. Because much of Australia's population is in urban areas, rewilding efforts must include urban areas to maximize effectiveness. Thus rewilding is not synonymous with wilderness and can occur over multiple scales. Rewilding efforts must recognize human effects on other species and benefit both nature and humans. Rewilding in Australia requires development of a shared vision and strategy and proof-of-concept projects to demonstrate the benefits. The repackaging of existing conservation activities as rewilding may confuse and undermine the success of rewilding programs and should be avoided. As elsewhere, rewilding in Australia should be viewed as an important conservation tool.
Una Perspectiva Australiana del Proceso de Resilvestrar Resumen El proceso de resilvestrar es reconocido cada vez más como una herramienta de conservación, pero con frecuencia depende del contexto ambiental, lo que inhibe su aplicación generalizada. En Australia, el proceso de resilvestrar busca mejorar la función ambiental y promover los ecosistemas auto-sustentables. Una ausencia de herbívoros nativos corpulentos significa que el resilvestreo trófico en la isla principal de Australia se ha enfocado en la restauración de las funciones que proporcionan los superdepredadores y los mamíferos pequeños. Debido a la influencia generalizada de los mesodepredadores introducidos, los cercos contra depredadores y el establecimiento de poblaciones en islas libres de depredadores son estrategias comunes de resilvestreo. Esto coloca al resilvestreo australiano aparte del que ocurre en muchas jurisdicciones y proporciona información relevante a nivel mundial, pero presenta retos para la restauración de la función en paisajes más amplios. El resilvestreo pasivo es de utilidad limitada en las zonas áridas. Aunque el aumento de la extensión del hábitat y la calidad en las áreas meso-costeras puede funcionar, probablemente sea necesario emprender un manejo activo. Ya que la mayoría de la población de Australia se encuentra en áreas urbanas, los esfuerzos de resilvestreo deben incluir a las áreas urbanas para maximizar su efectividad. Por lo tanto, el resilvestreo no es sinónimo de la naturaleza y puede ocurrir en múltiples escalas. Los esfuerzos de resilvestreo deben reconocer los efectos que los humanos tienen sobre otras especies y deben beneficiar a la naturaleza y a las personas. El resilvestreo en Australia requiere del desarrollo de una visión compartida y de proyectos con prueba de concepto para demostrar sus beneficios. La reinvención de las actividades de conservación existentes como resilvestreo podría confundir y debilitar el éxito de los programas de resilvestreo, por lo que debería evitarse. Como en todos lados, el proceso de resilvestrar en Australia debería verse como una herramienta importante de conservación.
Assuntos
Conservação dos Recursos Naturais , Ecossistema , Animais , Austrália , Biodiversidade , Humanos , Meio SelvagemRESUMO
BACKGROUND/OBJECTIVE: Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer's disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson's disease, and (5) vascular cognitive impairment. METHODS: Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases. RESULTS: Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy. CONCLUSION: This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Étude de variance génétique dans le cadre de l'initiative de recherche sur les maladies neurodégénératives en Ontario. Contexte/Objectif : L'apolipoprotéine E4 (ApoE4) constitue le principal facteur de risque génétique de la maladie d'Alzheimer. En raison de cette association systématique, il existe un intérêt certain à savoir dans quelle mesure cette classe d'apolipoprotéines peut influencer le risque d'autres maladies neurodégénératives. En outre, le milieu de la recherche n'a de cesse d'identifier d'autres biomarqueurs génétiques, par exemple les haplotypes H1 de la protéine tau associée aux microtubules, qui contribuent à certains phénotypes, Dans le cadre de cette étude, des participants à l'initiative de recherche sur les maladies neurodégénératives en Ontario ont été « génotypés ¼ afin de déterminer si l'ApoE4 ou l'haplotype H1 mentionné ci-dessus peuvent être associés à cinq maladies neurodégénératives : 1) la maladie d'Alzheimer et d'autres troubles cognitifs légers ; 2) la sclérose latérale amyotrophique ; 3) la démence fronto-temporale ; 4) la maladie de Parkinson ; 5) et finalement les déficits cognitifs d'origine vasculaire. Méthodes : Pour chaque participant, la cartographie des génotypes a été établie en fonction de leur ApoE4 respectif et de la présence d'haplotypes H1 de la protéine tau associée aux microtubules. Des analyses de régression logistique ont été ensuite effectuées dans le but d'identifier de possibles liens avec ces maladies neurodégénératives. Résultats : Nos travaux ont confirmé l'association entre l'ApoE4 et une plus grande occurrence de cas d'Alzheimer, et ce, en tenant compte de l'effet d'une dose de médicament. Ils ont aussi montré une association entre la seule ApoE4 et des troubles cognitifs légers. Cela dit, il convient de préciser que les quatre autres maladies n'ont pas été associées à cet allèle. Plus encore, nous avons trouvé que l'allèle E2 de l'apolipoprotéine était associé à une occurrence plus faible de cas d'Alzheimer et de troubles cognitifs légers. Fait à souligner, aucune association n'a été détectée entre l'haplotype H1 de la protéine tau associée aux microtubules et nos cohortes atteintes de maladies neurodégénératives. Toutefois, à la suite du sous-typage de la cohorte de participants atteints de démence fronto-temporale, il s'est avéré que l'haplotype H1 était associé de façon notable à la paralysie supra-nucléaire progressive. Conclusion : Il s'agit de la première étude à analyser simultanément, au moyen de critères de participation cohérents et d'une analyse phénotypique élargie, les associations entre les isoformes de l'ApoE, l'haplotype H1 de la protéine tau associée aux microtubules et cinq maladies neurodégénératives.
Assuntos
Apolipoproteínas E/genética , Predisposição Genética para Doença/genética , Doenças Neurodegenerativas/genética , Proteínas tau/genética , Idoso , Apolipoproteína E4/genética , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , OntárioRESUMO
NeuN is a nuclear protein expressed exclusively in mature neurons and has served for many years as a reliable neuronal marker in immunohistochemical labeling studies. In 2009, NeuN was identified as Fox3, one of three closely related RNA binding proteins important in pre-mRNA splicing. During the course of a previous study using G93A SOD1 mice, a model of amyotrophic lateral sclerosis (ALS), we observed that NeuN was significantly redistributed to the cytosol. Since altered splicing may be important in the pathogenesis of ALS, we compared the localization (predominantly nuclear or cytosolic) of all three Fox proteins in the lumbar spinal cord of wild-type and G93A SOD1 mice before and after the development of clinical signs of disease. The Fox proteins regulate their own splicing, and we also examined the major Fox protein isoforms in nuclear and cytosolic fractions of lumbar spinal cord by Western blotting. We report here that Fox3 and Fox2 undergo a major cytosolic relocalization in this ALS model that increases with age and that is associated with progressive alterations in the splicing profiles of all three Fox proteins.
Assuntos
Citosol/química , Neurônios Motores/química , Neurônios Motores/citologia , Proteínas do Tecido Nervoso/análise , Proteínas Nucleares/análise , Fatores de Processamento de RNA/análise , Animais , Citosol/metabolismo , Proteínas de Ligação a DNA , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Processamento de RNA/metabolismoRESUMO
MRI-negative anterior cingulate epilepsy is a rare entity. Herein, we describe a case of MRI and functional imaging-negative intractable frontal lobe epilepsy in which, initially, secondary bilateral synchrony of surface and intracranial EEG and non-lateralizing semiology rendered identification of the epileptogenic zone difficult. A staged bilateral stereotactic EEG exploration revealed a very focal, putative ictal onset zone in the right anterior cingulate gyrus, as evidenced by interictal and ictal high-frequency oscillations (at 250Hz) and induction of seizures from the same electrode contacts by 50-Hz low-intensity cortical stimulation. This was subsequently confirmed by ILAE class 1 outcome following resection of the ictal onset and irritative zones. Histopathological examination revealed focal cortical dysplasia type 1b (ILAE Commission, 2011) as the cause of epilepsy. The importance of anatomo-electro-clinical correlation is illustrated in this case in which semiological and electrophysiological features pointed to the anatomical localization of a challenging, MRI-negative epilepsy.
Assuntos
Epilepsias Parciais/diagnóstico , Epilepsia do Lobo Frontal/diagnóstico , Giro do Cíngulo/fisiopatologia , Malformações do Desenvolvimento Cortical/diagnóstico , Adulto , Anormalidades Craniofaciais , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
In this paper, a three-component decomposition algorithm is proposed for processing compact polarimetric SAR images. By using the correspondence between the covariance matrix and the Stokes vector, three-component scattering models for CTLR and DCP modes are established. The explicit expression of decomposition results is then derived by setting the contribution of volume scattering as a free parameter. The degree of depolarization is taken as the upper bound of the free parameter, for the constraint that the weighting factor of each scattering component should be nonnegative. Several methods are investigated to estimate the free parameter suitable for decomposition. The feasibility of this algorithm is validated by AIRSAR data over San Francisco and RADARSAT-2 data over Flevoland.
RESUMO
Amyotrophic lateral sclerosis (ALS) is proving intractable. Difficulties in pre-clinical studies contribute in small measure to this futility, but the chief reason for failure is an inadequate understanding of disease pathogenesis. Many acquired and inherited processes have been advanced as potential causes of ALS but, while they may predispose to disease, it seems increasingly likely that none leads directly to ALS. Rather, two recent overlapping considerations, both involving aberrant protein homeostasis, may provide a better explanation for a common disease phenotype and a common terminal pathogenesis. If so, therapeutic approaches will need to be altered and carefully nuanced, since protein homeostasis is essential and highly conserved. Nonetheless, these considerations provide new optimism in a difficult disease which has hitherto defied treatment.
Assuntos
Esclerose Lateral Amiotrófica/terapia , Proteínas/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Genótipo , Homeostase , Humanos , Fenótipo , Deficiências na Proteostase/genética , Deficiências na Proteostase/metabolismoRESUMO
BACKGROUND: The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis. RESULTS: Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture. CONCLUSIONS: Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro.
Assuntos
Proteínas Hedgehog/metabolismo , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Superóxido Dismutase/metabolismo , Esclerose Lateral Amiotrófica , Animais , Contagem de Células , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Imunofluorescência , Camundongos , Camundongos Transgênicos , Medula Espinal/citologia , Medula Espinal/embriologia , Medula Espinal/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase-1RESUMO
OBJECTIVE: The self-administered version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is used to monitor function and disease progression in individuals with amyotrophic lateral sclerosis (ALS). However, the performance of the self-administered ALSFRS-R has not been assessed using Rasch Measurement Theory. Therefore, the purpose of this study was to examine the psychometric properties of the self-administered ALSFRS-R using Rasch analysis. METHODS: Rasch analysis was performed on self-administered ALSFRS-R data from individuals with ALS across Canada. The following 6 aspects of Rasch analysis were examined using RUMM2030: fit via residuals and chi-square statistics, targeting via person-item threshold maps, dependency via item residual correlations, unidimensionality through principal components analysis of residuals, reliability via person separation index, and stability through differential item functioning analyses for sex, age, and language. RESULTS: Analysis was performed on 122 participants (mean age: 52.9 years; 62.8% men). The overall scale demonstrated good fit, reliability, and stability; however, multidimensionality was found. To address this issue, items were divided into 3 subscales (bulbar, motor, and respiratory function), and Rasch analysis was performed for each subscale. The subscales demonstrated good fit, reliability, stability, and unidimensionality. However, there were still issues with item dependency for all subscale and targeting for bulbar and respiratory subscales. CONCLUSIONS: The self-administered ALSFRS-R is reliable, internally valid, and stable across sex, age, and language subgroups; however, it is recommended that the ALSFRS-R be scored by subscale. Future studies can look at revising and/or adding items to tackle misfit, redundancy, and ceiling effects. IMPACT: Self-administered measures are simple to administer and inexpensive. The self-administered ALSFRS-R was found to be psychometrically sound and can be used as a tool to monitor disease progression and function in ALS.
Assuntos
Esclerose Lateral Amiotrófica , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Reprodutibilidade dos Testes , Idioma , Psicometria , Progressão da DoençaRESUMO
Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and cerebrovascular disease; n = 391, age 40-87) and healthy controls (n = 149, age 42-87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer's disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.
RESUMO
BACKGROUND: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. METHODS: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. RESULTS: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. CONCLUSIONS: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.
Assuntos
Transtornos Cerebrovasculares , Disfunção Cognitiva , Demência Frontotemporal , Doença de Parkinson , Substância Branca , Humanos , Feminino , Substância Branca/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Objective: The aim of this study was to refine the items of a preference-based amyotrophic lateral sclerosis health-related quality of life scale (PB-ALS HRQL scale) based on domains generated in a previous study. Methods: Survey methodology was used to assess item importance rating (IR) and independence. Median importance was calculated for each item and a rating of "very important" was required for the item to remain. Correlations were used to examine item independence. Highly correlated items (rs > 0.7) were considered for removal. Cognitive debriefing (CD) interviews, conducted by Zoom, telephone, or email based on participant preference and communication needs, were used to identify potential issues. Participants provided feedback about wording, clarity, response options, and recall period on randomly selected items. Items were considered finalized when three sequential CD participants approved the item with no revisions. Results: Thirty-four people with ALS (PALS, n = 16 females; age range 44-78 years; ALS Functional Rating Scale-Revised [ALSFRS-R] range 0-48) in Canada completed the survey; a subset of 18 PALS completed CD interviews (n = 8 female; age range 44-71 years; ALSFRS-R range 0-48). Four items were highly correlated with one or more items, were not rated as very important, or were not approved via CD and were removed. Conclusions: The final four-response option PB-ALS Scale includes eight items: recreation and leisure, mobility, interpersonal interactions and relationships, eating and swallowing, handling objects, communicating, routine activities, and mood. The next step is to translate the PB-ALS Scale into French and develop a scoring algorithm based on PALS' preferences.
Assuntos
Esclerose Lateral Amiotrófica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Esclerose Lateral Amiotrófica/psicologia , Qualidade de Vida , Inquéritos e Questionários , Deglutição/fisiologia , IdiomaRESUMO
Warming seas, marine heatwaves, and habitat degradation are increasingly widespread phenomena affecting marine biodiversity, yet our understanding of their broader impacts is largely derived from collective insights from independent localized studies. Insufficient systematic broadscale monitoring limits our understanding of the true extent of these impacts and our capacity to track these at scales relevant to national policies and international agreements. Using an extensive time series of co-located reef fish community structure and habitat data spanning 12 years and the entire Australian continent, we found that reef fish community responses to changing temperatures and habitats are dynamic and widespread but regionally patchy. Shifts in composition and abundance of the fish community often occurred within 2 years of environmental or habitat change, although the relative importance of these two mechanisms of climate impact tended to differ between tropical and temperate zones. The clearest of these changes on temperate and subtropical reefs were temperature related, with responses measured by the reef fish thermal index indicating reshuffling according to the thermal affinities of species present. On low latitude coral reefs, the community generalization index indicated shifting dominance of habitat generalist fishes through time, concurrent with changing coral cover. Our results emphasize the importance of maintaining local ecological detail when scaling up datasets to inform national policies and global biodiversity targets. Scaled-up ecological monitoring is needed to discriminate among increasingly diverse drivers of large-scale biodiversity change and better connect presently disjointed systems of biodiversity observation, indicator research, and governance.
Assuntos
Antozoários , Recifes de Corais , Animais , Antozoários/fisiologia , Austrália , Biodiversidade , Mudança Climática , Ecossistema , Peixes/fisiologiaRESUMO
BACKGROUND: Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. METHODS: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). RESULTS: In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1-5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7-11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. CONCLUSION: The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.
Assuntos
Variações do Número de Cópias de DNA , Doenças Neurodegenerativas , Éxons , Heterozigoto , Humanos , Doenças Neurodegenerativas/genética , FenótipoRESUMO
Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinson's disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.