Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

<p>Abstract</p> <p>Background</p> <p>Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored.</p> <p>Methods</p> <p>Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels.</p> <p>Results</p> <p>Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (<it>p </it>< 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (<it>p </it>< 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, <it>p </it>< 0.01), and inversely with memory scores in the late registration (σ = −0.276, <it>p </it>= 0.01) and early recall score (σ = −0.304, <it>p </it>= 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, <it>p </it>= 0.007) after controlling for the effect of age.</p> <p>Conclusions</p> <p>Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.</p

A Single Molecule Scaffold for the Maize Genome

About 85% of the maize genome consists of highly repetitive sequences that are interspersed by low-copy, gene-coding sequences. The maize community has dealt with this genomic complexity by the construction of an integrated genetic and physical map (iMap), but this resource alone was not sufficient for ensuring the quality of the current sequence build. For this purpose, we constructed a genome-wide, high-resolution optical map of the maize inbred line B73 genome containing >91,000 restriction sites (averaging 1 site/∼23 kb) accrued from mapping genomic DNA molecules. Our optical map comprises 66 contigs, averaging 31.88 Mb in size and spanning 91.5% (2,103.93 Mb/∼2,300 Mb) of the maize genome. A new algorithm was created that considered both optical map and unfinished BAC sequence data for placing 60/66 (2,032.42 Mb) optical map contigs onto the maize iMap. The alignment of optical maps against numerous data sources yielded comprehensive results that proved revealing and productive. For example, gaps were uncovered and characterized within the iMap, the FPC (fingerprinted contigs) map, and the chromosome-wide pseudomolecules. Such alignments also suggested amended placements of FPC contigs on the maize genetic map and proactively guided the assembly of chromosome-wide pseudomolecules, especially within complex genomic regions. Lastly, we think that the full integration of B73 optical maps with the maize iMap would greatly facilitate maize sequence finishing efforts that would make it a valuable reference for comparative studies among cereals, or other maize inbred lines and cultivars

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US), 10 mg twice daily, was approved by the US Food and Drug Administration (FDA) in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs) for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years). Commonly reported AEs (&ge;2% of all reported AEs) and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1), the most common AEs were dizziness (3.7%), insomnia (3.2%), balance disorder (3%), fall (2.4%), headache (2.4%), nausea (2.1%), and urinary tract infection (2%). Other common AEs were drug ineffectiveness (5.8%), gait disturbance (4.6%), and inappropriate dosing (3.1%). Serious AEs included rare anaphylactic reactions (five cases) and drug hypersensitivity reactions (eight cases). A total of 657 seizure cases were reported (6.3/1,000 patient-years); of these, 324 were medically confirmed (3.1/1,000 patient-years). Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to &gt;4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a warning regarding the risk of anaphylaxis and severe allergic reactions was added to the US prescribing information. Keywords: dalfampridine, fampridine, multiple sclerosis, adverse events, postmarketing safet