60 research outputs found
Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration.
The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from nonâdiseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMSâP, n = 9) or slow (PPMSâNP, n = 10) disease course based on worsening disability and/or MRIâvisible appearance of new T2 lesions over a oneâyearâassessment. Partial least squaresâdiscriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelinâd18:1/14:0 and monoâhexosylceramideâd18:1/20:0 were differentially abundant in the plasma of ppMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lysoâphosphatidic acidâ18:2 (LPAâ18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPAâ18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsingâremitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelinâd18:1/14:0, monoâhexosylceramideâd18:1/20:0, and LPAâ18:2 may represent important targets for future studies aimed at understanding disease progression in MS
Tracing controversies in hacker communities: ethical considerations for internet research
This paper reflects on the ethics of internet research on community controversies. Specifically, it focuses on controversies concerning gendered, social interaction in hacking communities. It addresses the question how internet researchers should treat and represent content that individuals controversially discussed online. While many internet sources are likewise technically public, they may yet suggest distinct privacy expectations on the part of involved individuals. In internet research, ethical decision-making regarding which online primary sources may be, e.g., referenced and quoted or require anonymisation is still ambiguous and contested. Instead of generalisable rules, the context dependence of internet research ethics has been frequently stressed. Given this ambiguity, the paper elaborates on ethical decisions and their implications by exploring the case of a controversial hackerspaces.org mailing list debate. In tracing data across different platforms, it analyses the emerging ethico-methodological challenges
The Usability of E-learning Platforms in Higher Education: A Systematic Mapping Study
The use of e-learning in higher education has increased significantly in recent years, which has led to several studies being conducted to investigate the usability of the platforms that support it. A variety of different usability evaluation methods and attributes have been used, and it has therefore become important to start reviewing this work in a systematic way to determine how the field has developed in the last 15 years. This paper describes a systematic mapping study that performed searches on five electronic libraries to identify usability issues and methods that have been used to evaluate e-learning platforms. Sixty-one papers were selected and analysed, with the majority of studies using a simple research design reliant on questionnaires. The usability attributes measured were mostly related to effectiveness, satisfaction, efficiency, and perceived ease of use. Furthermore, several research gaps have been identified and recommendations have been made for further work in the area of the usability of online learning
Oestrogen-induced angiogenesis and implantation contribute to the development of parasitic myomas after laparoscopic morcellation
Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration
The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing\u2013remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS
A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis
Multiple sclerosis is an autoimmune demyelinating disorder of the CNS, characterized by inflammatory lesions and an underlying neurodegenerative process, which is more prominent in patients with progressive disease course. It has been proposed that mitochondrial dysfunction underlies neuronal damage, the precise mechanism by which this occurs remains uncertain. To investigate potential mechanisms of neurodegeneration, we conducted a functional screening of mitochondria in neurons exposed to the CSF of multiple sclerosis patients with a relapsing remitting (n = 15) or a progressive (secondary, n = 15 or primary, n = 14) disease course. Live-imaging of CSF-treated neurons, using a fluorescent mitochondrial tracer, identified mitochondrial elongation as a unique effect induced by the CSF from progressive patients. These morphological changes were associated with decreased activity of mitochondrial complexes I, III and IV and correlated with axonal damage. The effect of CSF treatment on the morphology of mitochondria was characterized by phosphorylation of serine 637 on the dynamin-related protein DRP1, a post-translational modification responsible for unopposed mitochondrial fusion in response to low glucose conditions. The effect of neuronal treatment with CSF from progressive patients was heat stable, thereby prompting us to conduct an unbiased exploratory lipidomic study that identified specific ceramide species as differentially abundant in the CSF of progressive patients compared to relapsing remitting multiple sclerosis. Treatment of neurons with medium supplemented with ceramides, induced a time-dependent increase of the transcripts levels of specific glucose and lactate transporters, which functionally resulted in progressively increased glucose uptake from the medium. Thus ceramide levels in the CSF of patients with progressive multiple sclerosis not only impaired mitochondrial respiration but also decreased the bioavailability of glucose by increasing its uptake. Importantly the neurotoxic effect of CSF treatment could be rescued by exogenous supplementation with glucose or lactate, presumably to compensate the inefficient fuel utilization. Together these data suggest a condition of \u2018virtual hypoglycosis\u2019 induced by the CSF of progressive patients in cultured neurons and suggest a critical temporal window of intervention for the rescue of the metabolic impairment of neuronal bioenergetics underlying neurodegeneration in multiple sclerosis patients
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