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INTRODUCTION@#Detection of neurological conditions is of high importance in the current context of increasingly ageing populations. Imaging of the retina and the optic nerve head represents a unique opportunity to detect brain diseases, but requires specific human expertise. We review the current outcomes of artificial intelligence (AI) methods applied to retinal imaging for the detection of neurological and neuro-ophthalmic conditions.@*METHOD@#Current and emerging concepts related to the detection of neurological conditions, using AI-based investigations of the retina in patients with brain disease were examined and summarised.@*RESULTS@#Papilloedema due to intracranial hypertension can be accurately identified with deep learning on standard retinal imaging at a human expert level. Emerging studies suggest that patients with Alzheimer's disease can be discriminated from cognitively normal individuals, using AI applied to retinal images.@*CONCLUSION@#Recent AI-based systems dedicated to scalable retinal imaging have opened new perspectives for the detection of brain conditions directly or indirectly affecting retinal structures. However, further validation and implementation studies are required to better understand their potential value in clinical practice.
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Humans , Artificial Intelligence , Brain/diagnostic imaging , Retina , Optic Disk , AgingABSTRACT
This article considers the idea of medicine's internal morality as it is understood by its various proponents. Although the use of the phrase 'internal morality' in relation to medicine predates Edmund Pellegrino, he can be credited with cementing its place in the vocabulary of medical ethics. Yet, while 'internal morality' and its related terms are now readily recognizable, they are used to denote irreconcilable ideas. Our aims, therefore, are to, firstly, clarify and, secondly, evaluate the different uses of 'internal morality', showing that there is little agreement on its definition. Thirdly, we argue that the terminology relating to 'internal morality' requires substantial revision, and that the term itself should be jettisoned. Finally, we briefly set out our own account of how morality should be understood in relation to the practice of medicine along similar but clearer lines to Pellegrino.
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Medicine , Morals , Ethics, Medical , HumansABSTRACT
Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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ABSTRACT Objectives To analyze the strategies to control delayed onset muscle soreness (DOMS) and fatigue used by Brazilian paracanoe para-athletes. Methodology: 34 para-athletes were interviewed during the Brazilian canoeing championship in 2017. The interview was divided into four parts: athlete's personal data, disability characteristics, sport practice, and relationship of performance with fatigue and DOMS. Results: 91% of the para-athletes reported DOMS and 88% fatigue. However, despite feeling DOMS and fatigue, 70% of the para-athletes did not undertake prevention or recovery interventions. Conclusion: Although Brazilian paracanoe para-athletes reported intense and frequent DOMS and fatigue, they do not use any strategy to control or reduce them.
RESUMO Objetivos Analisar as estratégias de controle da dor muscular de início tardio (DMIT) e da fadiga utilizadas por atletas brasileiros de paracanoagem. Metodologia: 34 atletas foram entrevistados durante o campeonato brasileiro de canoagem 2017. A entrevista foi dividida em quatro partes: dados pessoais do atleta, características da deficiência, prática esportiva e relação do desempenho com a fadiga e a DMIT. Resultados: 91% relataram sentir DOMS e 88% fadiga. Porém, apesar de sentirem DMIT e fadiga, 70% dos atletas não realizaram intervenções de prevenção ou recuperação. Conclusão: Embora os atletas brasileiros de paracanoagem relatem intensa e frequente DMIT e fadiga, eles não utilizam nenhuma estratégia para controlá-los ou reduzi-los.
RESUMEN Objetivos Analizar las estrategias de control para el dolor muscular de inicio tardío (DOMS) y la fatiga utilizados por los atletas paracaidistas brasileños. Metodología: 34 atletas fueron entrevistados durante el campeonato brasileño de piragüismo 2017. La entrevista se dividió en cuatro partes: datos personales del atleta, características de discapacidad, práctica deportiva y relación de rendimiento con fatiga y DOMS. Resultados: 91% informó sentirse DOMS y el 88% fatiga. Sin embargo, apesar de sentir DOMS y fatiga, el 70% de los atletas no realizaron intervenciones de prevención o recuperación. Conclusión: Aunque los atletas paracaidistas brasileños reportaron DOMS intenso y frecuente y fatiga, no utilizan ninguna estrategia para controlarlos o reducirlos.
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There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.
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INTRODUCTION@#Singapore has a rapidly ageing population and an increasing prevalence of Alzheimer's disease (AD). Compliance to AD medications is associated with treatment effectiveness. We investigated compliance to acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist and treatment persistence among patients seen at the General Memory Clinic of National University Hospital, Singapore. We also identified the reasons for non-compliance.@*METHODS@#Patients seen at the General Memory Clinic between 1 January 2013 and 31 December 2014, who were prescribed AChEIs and NMDA receptor antagonist, were included in this retrospective cohort study. Non-compliance to medications was indirectly measured by failure to renew prescription within 60 days of the last day of medication supplied by the previous prescription. The reasons for non-compliance were identified.@*RESULTS@#A total of 144 patients were included. At one year, 107 patients were compliant to AD medications, while 37 patients were non-compliant. Around 60% of the non-compliant patients discontinued the use of AD medications within the first six months, and the mean persistent treatment period among this group of patients was 10.3 ± 3.5 months. The main reason for non-compliance was patients' and caregivers' perception that memory loss was of lower priority than other coexisting illnesses. Other reasons for non-compliance included side effects of medications (18.9%), perceived ineffectiveness of treatment (16.2%), inability to attend clinic (5.4%) and high cost of medications (2.7%).@*CONCLUSION@#Our findings suggest that the reasons for medication non-compliance can be identified early. Better compliance may be achieved through a multidisciplinary approach to patient education.
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Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease , Drug Therapy , Epidemiology , Psychology , Caregivers , Cholinesterase Inhibitors , Therapeutic Uses , Drug Costs , Interdisciplinary Communication , Medication Adherence , Patient Compliance , Quality of Life , Receptors, N-Methyl-D-Aspartate , Retrospective Studies , Singapore , Epidemiology , Treatment OutcomeABSTRACT
Tauopathies are neurodegenerative diseases that are characterized by the presence of hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain and include Alzheimer's disease and frontotemporal dementia, which lack effective disease-modifying treatments. The presence of NFTs is known to correlate with cognition impairment, suggesting that targeting tau hyperphosphorylation may be therapeutically effective. MLC901 is a herbal formulation that is currently used in poststroke recovery and consists of nine herbal components. Previously, several components of MLC901 have been shown to have an effect on tau phosphorylation, but it remains unknown whether MLC901 itself has the same effect. The objective of this study was to assess the effects of MLC901 on ameliorating tau phosphorylation at epitopes associated with NFT formation. A stably transfected cell culture model expressing tau harboring the P301S mutation was generated and treated with various concentrations of MLC901 across different time points. Tau phosphorylation profiles and protein levels of enzymes associated with tau phosphorylation were assessed using western blotting. One-way analysis of variance with Bonferroni post-hoc analysis showed that MLC901 significantly reduced tau phosphorylation at epitopes recognized by the AT8, AT270, and PHF-13 antibodies. MLC901 also induced a significant increase in the s9 phosphorylation of glycogen synthase kinase 3ß and a concurrent decrease in the activation of cyclin-dependent kinase 5, as measured by a significant decrease in the levels of p35/cyclin-dependent kinase 5. Our results provide supporting evidence to further study the effects of MLC901 on tau pathology and cognition using mouse models of tauopathy.
