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- Blacher, E., et al.
(författare)
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Potential roles of gut microbiome and metabolites in modulating ALS in mice
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7770, s. 474-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.
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- Andermann, E., et al.
(författare)
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Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures
- 2018
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 82, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. Methods: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400 mg (studies 301 and 302 only), 800 mg, or 1200 mg once daily (QD) for 14 weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. Results: The analysis population included 1447 patients (ESL, n = 1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p = 0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p = 0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p = 0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200 mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs were (0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL. and 0.7% and 0.5% taking placebo, respectively. Conclusions: In phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. The incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo. © 2017
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- Biton, Shany, et al.
(författare)
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Estimation of f-wave Dominant Frequency Using a Voting Scheme
- 2022
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Ingår i: Computing in Cardiology, CinC 2022. - 9798350300970
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Konferensbidrag (refereegranskat)abstract
- Atrial fibrillation (AF) is the most common heart arrhythmia, characterized by the presence of fibrillatory waves (f-waves) in the ECG. We introduce a voting scheme to estimate the dominant atrial frequency (DAF) of f-waves. Methods: We analysed a subset of Holter recordings obtained from the University of Virginia AF Database. 100 Holter recordings with manually annotated AF events, resulting in a total 363 AF events lasting more than 1 min. The f-waves were extracted using four different template subtraction (TS) algorithms and the DAF was estimated from the first 1-min window of each AF event. A random forest classifier was used. We hypothesized that better extraction of the f-wave meant better AF/non-AF classification using the DAF as the single input feature of the RF model. Results: Performance on the test set, expressed in terms of AF/non-AF classification, was the best when the DAF was computed computed the three best-performing extraction methods. Using these three algorithms in a voting scheme, the classifier obtained AUC=0.60 and the DAFs were mostly spread around 6 Hz, 5.66 (4.83-7.47). Conclusions: This study has two novel contributions: (1) a method for assessing the performance of f-wave extraction algorithms, and (2) a voting scheme for improved DAF estimation.
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