Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
EClinicalMedicine ; 69: 102437, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38544796

RESUMO

Background: Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. Methods: In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Findings: Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. Interpretation: These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. Funding: The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

2.
Chemosphere ; 349: 140890, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072201

RESUMO

There is much interest in developing metal-free halogenated graphene such as fluorinated graphene for various catalytic applications. In this work, a fluorine-doped graphene oxide photocatalyst was investigated for photocatalytic oxidation (PCO) of a volatile organic compound (VOC), namely gaseous methanol. The fluorination process of graphene oxide (GO) was carried out via a novel and facile solution-based photoirradiation method. The fluorine atoms were doped on the surface of the GO in a semi-ionic C-F bond configuration. This presence of the semi-ionic C-F bonds induced a dramatic 7-fold increment of the hole charge carrier density of the photocatalyst. The fluorinated GO photocatalyst exhibited excellent photodegradation up to 93.5% or 0.493 h-1 according pseudo-first order kinetics for methanol. In addition, 91.7% of methanol was mineralized into harmless carbon dioxide (CO2) under UV-A irradiation. Furthermore, the photocatalyst demonstrated good stability in five cycles of methanol PCO. Besides methanol, other VOCs such as acetone and formaldehyde were also photodegraded. This work reveals the potential of fluorination in producing effective graphene-based photocatalyst for VOC removal.


Assuntos
Grafite , Compostos Orgânicos Voláteis , Grafite/química , Metanol/química , Flúor/química
3.
JAMA Neurol ; 81(2): 134-142, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38147328

RESUMO

Importance: There is limited information on modifiable risk factors for young-onset dementia (YOD). Objective: To examine factors that are associated with the incidence of YOD. Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023. Exposures: A total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic factors (apolipoprotein E), lifestyle factors (physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage), environmental factors (nitrogen oxide, particulate matter, pesticide, and diesel), blood marker factors (vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin), cardiometabolic factors (stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use), psychiatric factors (depression, anxiety, benzodiazepine use, delirium, and sleep problems), and other factors (traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength). Main Outcome and Measures: Multivariable Cox proportional hazards regression was used to study the association between the risk factors and incidence of YOD. Factors were tested stepwise first within domains and then across domains. Results: Of 356 052 included participants, 197 036 (55.3%) were women, and the mean (SD) age at baseline was 54.6 (7.0) years. During 2 891 409 person-years of follow-up, 485 incident YOD cases (251 of 485 men [51.8%]) were observed, yielding an incidence rate of 16.8 per 100 000 person-years (95% CI, 15.4-18.3). In the final model, 15 factors were significantly associated with a higher YOD risk, namely lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression. Conclusions and Relevance: In this study, several factors, mostly modifiable, were associated with a higher risk of YOD. These modifiable risk factors should be incorporated in future dementia prevention initiatives and raise new therapeutic possibilities for YOD.


Assuntos
Alcoolismo , Demência , Diabetes Mellitus , Perda Auditiva , Cardiopatias , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Alcoolismo/complicações , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , Proteína C-Reativa , Força da Mão , Demência/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Cardiopatias/complicações , Apolipoproteínas , Perda Auditiva/complicações
4.
Curr Neurol Neurosci Rep ; 23(11): 801-813, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37957525

RESUMO

PURPOSE OF REVIEW: To review the literature examining the relationship between sleep and cognition, specifically examining the sub-domain of executive function. We explore the impact of sleep deprivation and the important question of how much sleep is required for optimal cognitive performance. We consider how other sleep metrics, such as sleep quality, may be a more meaningful measure of sleep. We then discuss the putative mechanisms between sleep and cognition followed by their contribution to developing dementia. RECENT FINDINGS: Sleep duration and executive function display a quadratic relationship. This suggests an optimal amount of sleep is required for daily cognitive processes. Poor sleep efficiency and sleep fragmentation are linked with poorer executive function and increased risk of dementia during follow-up. Sleep quality may therefore be more important than absolute duration. Biological mechanisms which may underpin the relationship between sleep and cognition include brain structural and functional changes as well as disruption of the glymphatic system. Sleep is an important modifiable lifestyle factor to improve daily cognition and, possibly, reduce the risk of developing dementia. The impact of optimal sleep duration and sleep quality may have important implications for every ageing individual.


Assuntos
Demência , Função Executiva , Humanos , Adulto , Duração do Sono , Cognição , Sono , Privação do Sono/complicações , Privação do Sono/psicologia , Demência/etiologia
5.
Alzheimers Dement ; 19(12): 5952-5969, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837420

RESUMO

INTRODUCTION: A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding. METHODS: ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field. RESULTS: Risk-profiling tools may help identify high-risk populations for clinical trials; however, their performance needs improvement. New risk-profiling and trial-recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug-repurposing efforts and prioritization of disease-modifying therapeutics. DISCUSSION: ML is not yet widely used but has considerable potential to enhance precision in dementia prevention. HIGHLIGHTS: Artificial intelligence (AI) is not widely used in the dementia prevention field. Risk-profiling tools are not used in clinical practice. Causal insights are needed to understand risk factors over the lifespan. AI will help personalize risk-management tools for dementia prevention. AI could target specific patient groups that will benefit most for clinical trials.


Assuntos
Inteligência Artificial , Demência , Humanos , Aprendizado de Máquina , Fatores de Risco , Desenvolvimento de Medicamentos , Demência/prevenção & controle
6.
Biochim Biophys Acta Rev Cancer ; 1878(5): 188949, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37399979

RESUMO

Leukemia is a malignancy of the hematopoietic system, and as its pathogenesis has become better understood, three generations of tyrosine kinase inhibitors (TKIs) have been developed. Ponatinib is the third-generation breakpoint cluster region (BCR) and Abelson (ABL) TKI, which has been influential in the leukemia therapy for a decade. Moreover, ponatinib is a potent multi-target kinase inhibitor that acts on various kinases, such as KIT, RET, and Src, making it a promising treatment option for triple-negative breast cancer (TNBC), lung cancer, myeloproliferative syndrome, and other diseases. The drug's significant cardiovascular toxicity poses a significant challenge to its clinical use, requiring the development of strategies to minimize its toxicity and side effects. In this article, the pharmacokinetics, targets, therapeutic potential, toxicity and production mechanism of ponatinib will be reviewed. Furthermore, we will discuss methods to reduce the drug's toxicity, providing new avenues for research to improve its safety in clinical use.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Proteínas de Fusão bcr-abl/farmacologia , Proteínas de Fusão bcr-abl/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Antineoplásicos/uso terapêutico
7.
JAMA Neurol ; 80(5): 445-454, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36972059

RESUMO

Importance: Epilepsy has been associated with cognitive impairment and potentially dementia in older individuals. However, the extent to which epilepsy may increase dementia risk, how this compares with other neurological conditions, and how modifiable cardiovascular risk factors may affect this risk remain unclear. Objective: To compare the differential risks of subsequent dementia for focal epilepsy compared with stroke and migraine as well as healthy controls, stratified by cardiovascular risk. Design, Setting, and Participants: This cross-sectional study is based on data from the UK Biobank, a population-based cohort of more than 500 000 participants aged 38 to 72 years who underwent physiological measurements and cognitive testing and provided biological samples at 1 of 22 centers across the United Kingdom. Participants were eligible for this study if they were without dementia at baseline and had clinical data pertaining to a history of focal epilepsy, stroke, or migraine. The baseline assessment was performed from 2006 to 2010, and participants were followed up until 2021. Exposures: Mutually exclusive groups of participants with epilepsy, stroke, and migraine at baseline assessment and controls (who had none of these conditions). Individuals were divided into low, moderate, or high cardiovascular risk groups based on factors that included waist to hip ratio, history of hypertension, hypercholesterolemia, diabetes, and smoking pack-years. Main Outcomes and Measures: Incident all-cause dementia; measures of executive function; and brain total hippocampal, gray matter, and white matter hyperintensity volumes. Results: Of 495 149 participants (225 481 [45.5%] men; mean [SD] age, 57.5 [8.1] years), 3864 had a diagnosis of focal epilepsy only, 6397 had a history of stroke only, and 14 518 had migraine only. Executive function was comparable between participants with epilepsy and stroke and worse than the control and migraine group. Focal epilepsy was associated with a higher risk of developing dementia (hazard ratio [HR], 4.02; 95% CI, 3.45 to 4.68; P < .001), compared with stroke (HR, 2.56; 95% CI, 2.28 to 2.87; P < .001), or migraine (HR, 1.02; 95% CI, 0.85 to 1.21; P = .94). Participants with focal epilepsy and high cardiovascular risk were more than 13 times more likely to develop dementia (HR, 13.66; 95% CI, 10.61 to 17.60; P < .001) compared with controls with low cardiovascular risk. The imaging subsample included 42 353 participants. Focal epilepsy was associated with lower hippocampal volume (mean difference, -0.17; 95% CI, -0.02 to -0.32; t = -2.18; P = .03) and lower total gray matter volume (mean difference, -0.33; 95% CI, -0.18 to -0.48; t = -4.29; P < .001) compared with controls. There was no significant difference in white matter hyperintensity volume (mean difference, 0.10; 95% CI, -0.07 to 0.26; t = 1.14; P = .26). Conclusions and Relevance: In this study, focal epilepsy was associated with a significant risk of developing dementia, to a greater extent than stroke, which was magnified substantially in individuals with high cardiovascular risk. Further findings suggest that targeting modifiable cardiovascular risk factors may be an effective intervention to reduce dementia risk in individuals with epilepsy.


Assuntos
Doenças Cardiovasculares , Demência , Epilepsias Parciais , Epilepsia , Transtornos de Enxaqueca , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Feminino , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Fatores de Risco de Doenças Cardíacas , Epilepsias Parciais/epidemiologia , Epilepsia/epidemiologia , Demência/epidemiologia , Demência/etiologia , Transtornos de Enxaqueca/epidemiologia
8.
JAMA Ophthalmol ; 141(1): 84-91, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394831

RESUMO

Importance: Several ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA). Objective: To perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease. Data Sources: MEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched. Study Selection: Systematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk Of Bias in Systematic reviews tool was used to assess review quality. Main Outcomes and Measures: The prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference. Results: From the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88). Conclusions and Relevance: This umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Estudos Transversais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/complicações , Retina , Biomarcadores
9.
Lancet Healthy Longev ; 3(6): e428-e436, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35711612

RESUMO

Background: Individual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes. Methods: We examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006-10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics. Findings: The dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39-9·08, p<0·0001, and 1·68, 1·53-1·84, p<0·0001, respectively). Participants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia (HR 5·74, 95% CI 4·26-7·74, p<0·0001), compared with those with a low genetic risk and no cardiometabolic conditions. Crucially, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume (F2, 12 110 = 10·70; p<0·0001) and total grey matter volume (F2, 12 236 = 55·65; p<0·0001). Interpretation: Cardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk. Funding: Wellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.


Assuntos
Demência , Diabetes Mellitus , Humanos , Multimorbidade , Estudos Prospectivos , Fatores de Risco , Estados Unidos
10.
Commun Biol ; 5(1): 201, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241774

RESUMO

Sleep is essential for life, including daily cognitive processes, yet the amount of sleep required for optimal brain health as we grow older is unclear. Poor memory and increased risk of dementia is associated with the extremes of sleep quantity and disruption of other sleep characteristics. We examined sleep and cognitive data from the UK Biobank (N = 479,420) in middle-to-late life healthy individuals (age 38-73 years) and the relationship with brain structure in a sub-group (N = 37,553). Seven hours of sleep per day was associated with the highest cognitive performance which decreased for every hour below and above this sleep duration. This quadratic relationship remained present in older individuals (>60 years, N = 212,006). Individuals who sleep between six-to-eight hours had significantly greater grey matter volume in 46 of 139 different brain regions including the orbitofrontal cortex, hippocampi, precentral gyrus, right frontal pole and cerebellar subfields. Several brain regions showed a quadratic relationship between sleep duration and volume while other regions were smaller only in individuals who slept longer. These findings highlight the important relationship between the modifiable lifestyle factor of sleep duration and cognition as well as a widespread association between sleep and structural brain health.


Assuntos
Função Executiva , Imageamento por Ressonância Magnética , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Substância Cinzenta , Humanos , Pessoa de Meia-Idade , Sono
11.
ChemMedChem ; 17(3): e202100676, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34773680

RESUMO

In this study, a series of curcumin derivatives containing 1,2,3-triazole were designed and synthesized, and their inhibitory activities against the proliferation of lung cancer cells were studied. Compound 5 k (3,4-dichlorobenzyltriazole methyl curcumin) had the best activity against A549 cells, with a half-maximal inhibitory concentration (IC50 ) of 2.27 µM, which was approximately 10 times higher than that of the lead curcumin and higher than that of gefitinib (IC50 =8.64 µM). Western blotting revealed that 5 k increased the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Compound 5 k also promoted the expression of the inhibitor of nuclear factor-κB (IκBα) and decreased that of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and ß-catenin. Therefore, 5 k suppresses A549 cell proliferation by activating the mitogen-activated protein kinases and suppressing NF-κB/STAT3 signaling pathways. So, 5 k can potentially be used for treating non-small cell lung cancer.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Curcumina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Triazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Curcumina/síntese química , Curcumina/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Picratos/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química , Peixe-Zebra
12.
Epilepsy Behav ; 123: 108261, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481281

RESUMO

The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. OBJECTIVES: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. METHODS: We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. RESULTS: Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. CONCLUSION: Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic.


Assuntos
COVID-19 , Epilepsia , Brasil/epidemiologia , Epilepsia/epidemiologia , Humanos , Pandemias , SARS-CoV-2
13.
Int J Biol Macromol ; 189: 124-134, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34419536

RESUMO

Polyporus umbellatus (Pers.) Fries, a well-known medicinal fungus, has been reported to exhibit important functions of diuresis and dampness infiltration in traditional Chinese Medicine. Accumulating evidences have demonstrated that the P. umbellatus polysaccharides (PUPs) are the main and representative pharmacologically active ingredients and display multiple bioactivities both in vivo and in vitro methods, such as those of antioxidant, immunomodulatory, antitumor, anti-proliferative and hepatoprotective. Besides, many PUPs have been isolated from the different sources of P. umbellatus, including sclerotia, fruiting body, mycelia and fermentation liquid of this fungus. The purpose of the present review is to comprehensively and systematically reorganize the available information related to the extraction, purification, modification, structure characterization and to discuss diverse biological activities of PUPs to support their potential application value in pharmaceuticals field, functional foods and cosmetics areas. In addition, new invaluable insights on the future research with PUPs have also been proposed in the important areas of structural characterization and pharmacological activities.


Assuntos
Polyporus/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Fenômenos Químicos , Humanos , Fatores Imunológicos/farmacologia , Polissacarídeos/ultraestrutura
14.
Trials ; 22(1): 508, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332638

RESUMO

BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Animais , Estudos Cross-Over , Método Duplo-Cego , Humanos , Levetiracetam/efeitos adversos , Camundongos , Estudo de Prova de Conceito , Qualidade de Vida
15.
Nat Commun ; 11(1): 4340, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895386

RESUMO

Healthy cognitive ageing is a societal and public health priority. Cerebrovascular risk factors increase the likelihood of dementia in older people but their impact on cognitive ageing in younger, healthy brains is less clear. The UK Biobank provides cognition and brain imaging measures in the largest population cohort studied to date. Here we show that cognitive abilities of healthy individuals (N = 22,059) in this sample are detrimentally affected by cerebrovascular risk factors. Structural equation modelling revealed that cerebrovascular risk is associated with reduced cerebral grey matter and white matter integrity within a fronto-parietal brain network underlying executive function. Notably, higher systolic blood pressure was associated with worse executive cognitive function in mid-life (44-69 years), but not in late-life (>70 years). During mid-life this association did not occur in the systolic range of 110-140 mmHg. These findings suggest cerebrovascular risk factors impact on brain structure and cognitive function in healthy people.


Assuntos
Encéfalo/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Envelhecimento Saudável , Adulto , Idoso , Pressão Sanguínea , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Estudos de Coortes , Função Executiva/fisiologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Substância Branca/fisiopatologia
16.
Microorganisms ; 8(2)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102406

RESUMO

Understanding the effects of pollution on ecological communities and the underlying mechanisms that drive them will helpful for selecting a method to mediate polluted ecosystems. Quantifying the relative importance of deterministic and stochastic processes is a very important issue in ecology. However, little is known about their effects on the succession of microbial communities in different pollution levels rural ponds. Also, the processes that govern bacterial communities in polluted ponds are poorly understood. In this study, the microbial communities in water and sediment from the ponds were investigated by using the 16S rRNA gene high-throughput sequencing technology. Meanwhile, we used null model analyses based on a taxonomic and phylogenetic metrics approach to test the microbial community assembly processes. Pollution levels were found to significantly alter the community composition and diversity of bacteria. In the sediment samples, the bacterial diversity indices decreased with increasing pollutant levels. Between-community analysis revealed that community assembly processes among water and sediment samples stochastic ratio both gradually decreased with the increased pollution levels, indicating a potential deterministic environmental filtering that is elicited by pollution. Our results identified assemblage drivers of bacterial community is important for improving the efficacies of ecological evaluation and remediation for contaminated freshwater systems.

17.
FEMS Microbiol Ecol ; 96(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32016365

RESUMO

The plant-microbe interaction can affect ecosystem function, and many studies have demonstrated that plant species influence relevant microorganisms. In this study, microbial communities in bulk soil, rhizosphere soil and phyllosphere from different maize varieties were investigated using high-throughput sequencing method. Results demonstrated that cultivar Gaoneng 1 (G1) showed higher bacterial diversity in soil (both bulk and rhizosphere soils) and lower bacterial diversity in the phyllosphere, while cultivar Gaoneng 2 (G2) had lower fungal diversity in both the soil and phyllosphere compare to the other cultivars. The bacterial community structure of soils among the three varieties was significantly different; however, no significant differences were found in the soil fungal community and phyllosphere bacterial and fungal community. The soil networks from cultivar G1 and phyllosphere networks from cultivar Zhengdan (ZD) have the highest complexity in contrast to the other two cultivars. In conclusion, the bacterial community structure in bulk soil of different cultivars was significantly different, so do the co-occurrence ecological networks of phyllosphere bacterial community. This study comprehensively analyzed the microbial community among different maize cultivars and could be useful for guiding practices, such as evaluation of new plant cultivars and quality predictions of these varieties at the microbial level.


Assuntos
Micobioma , Rizosfera , Raízes de Plantas , Solo , Microbiologia do Solo , Zea mays
18.
RSC Adv ; 10(62): 37905-37915, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-35515183

RESUMO

Graphene oxide (GO) and reduced graphene oxide (rGO) can act as metal-free photocatalysts to remove aqueous dye pollutants under light illumination. However, there is some disparity in past reports on the origin of the photoactivity of GO and rGO for photodegradation of dye pollutants. In this work, the photoactivity of GO and rGO for methylene blue (MB) dye photodegradation were investigated with photoelectrochemical (PEC) measurements. The optimized rGO sample (G-2) exhibited a stable photocatalytic rate, which was 2.5 times higher than that of pure GO. PEC measurements revealed that the photocatalytic activity of G-2 was elevated due to higher photocurrent density, higher charge carrier density, and better charge separation. The changes in band gap and band positions of rGO were determined through optical characterization and Mott-Schottky (M-S) plots. Finally, the photocatalytic degradation mechanism of GO and rGO on MB dye was determined.

19.
Sci Total Environ ; 667: 691-700, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30849609

RESUMO

Bioremediation of organic pollutants has been identified as an economically efficient and environmentally friendly method. Here, a pot experiment was conducted to evaluate the bioremediation efficiency of dibutyl phthalate (DBP) by Gordonia phthalatica sp. nov. QH-11 in agricultural soils, along with the effect of this exogenous organism on the native microbial community and ecosystem functions during the bioremediation process. The results showed that inoculation with strain QH-11 accelerated DBP degradation in the soil and decreased DBP accumulation in plants, thereby reducing the health risks associated with vegetables grown in those soils. High-throughput sequencing demonstrated that both DBP contamination and the bioremediation process significantly altered prokaryotic community composition, structure, and network interactions; however, these effects were greatly reduced after 30 d. Dibutyl phthalate affected the prokaryotic community by influencing soil properties rather than directly impacting on microorganisms. In addition, ecosystem functions, like the nitrogen cycle, were significantly altered. Contamination with DBP promoted nitrogen fixation and the denitrification processes while inhibiting nitrification. Bioremediation may mitigate some of the changes to nitrogen cycling, helping to maintain the balance of prokaryotic community function. According to this study, bioremediation through highly efficient degradation bacteria may be a safe and promising method for reducing PAEs contamination in soil-vegetable systems.


Assuntos
Biodegradação Ambiental , Dibutilftalato/metabolismo , Bactéria Gordonia/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismo , Agricultura , Ecossistema , Solo
20.
RSC Adv ; 9(31): 18076-18086, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35520578

RESUMO

Nowadays, humans spend most of their time indoors and are frequently exposed to volatile organic compounds (VOCs) from various sources. The photocatalytic oxidation (PCO) method is a relatively more efficient method than the adsorption method for removing VOCs from the environment. In this work, graphene oxide (GO) was partially reduced via photoreduction under ultraviolet light (UV-A) irradiation and then used as a photocatalyst to degrade VOCs. After photoreduction, the band gap of the partially reduced graphene oxide (PRGO) decreased from 3.5-4.5 eV to 3.1-4.0 eV. Methanol vapour, which acts as a model VOC, was photodegraded using the PRGO. The effectiveness of the PRGO was mainly due to the removal of oxygen functional groups and restoration of the sp2 domain. This lowered the band gap and slowed down the electron recombination rate, which resulted in a higher photocatalytic activity. The photocatalytic activity of PRGO followed pseudo-first order kinetics, with a rate constant of 0.0025 min-1, and it could be reused for five cycles without any significant loss in the photocatalytic activity. This study demonstrates the potential of PRGO as a versatile and stable metal-free photocatalyst to remove indoor pollutants.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...