Correction: Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice.
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ABSTRACT:
SUBMITTER: Villani C
PROVIDER: S-EPMC6025955 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Correction: Lovastatin fails to improve motor performance and survival in <i>methyl-CpG-binding protein2</i>-null mice.
Villani Claudia C Sacchetti Giuseppina G Bagnati Renzo R Passoni Alice A Fusco Federica F Carli Mirjana M Invernizzi Roberto William RW
eLife 20180629
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Project description:Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous study) had no effects on motor deficits and survival when Mecp2 deletion was expressed on a background strain (C57BL/6J; B6) differing from that used in the earlier study. These findings indicate that the effects of statins may be background specific and raise important issues to consider when contemplating clinical trials. The reduction of the brain cholesterol metabolite 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in brain cholesterol metabolism and the potential utility of using plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT.
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Project description:BackgroundAs broader geographic sharing is implemented in lung transplant allocation through the Composite Allocation Score (CAS) system, models predicting waitlist and posttransplant (PT) survival will become more important in determining access to organs.Research questionHow well do CAS survival models perform, and can discrimination performance be improved with alternative statistical models or machine learning approaches?Study design and methodsScientific Registry for Transplant Recipients (SRTR) data from 2015-2020 were used to build seven waitlist (WL) and data from 2010-2020 to build similar PT models. These included the (I) current lung allocation score (LAS)/CAS model; (II) re-estimated WL-LAS/CAS model; (III) model II incorporating nonlinear relationships; (IV) random survival forests model; (V) logistic model; (VI) linear discriminant analysis; and (VII) gradient-boosted tree model. Discrimination performance was evaluated at 1, 3, and 6 months on the waiting list and 1, 3, and 5 years PT. Area under the curve (AUC) values were estimated across subgroups.ResultsWL model performance was similar across models with the greatest discrimination in the baseline cohort (AUC 0.93) and declined to 0.87-0.89 for 3-month and 0.84-0.85 for 6-month predictions and further diminished for residual cohorts. Discrimination performance for PT models ranged from AUC 0.58-0.61 and remained stable with increasing forecasting times but was slightly worse for residual cohorts. WL and PT variability in AUC was greatest for individuals with Medicaid insurance.InterpretationUse of alternative modeling strategies and contemporary cohorts did not improve performance of models determining access to lung transplant.
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Project description:We investigated if a carbohydrate (CHO) mouth rinse may attenuate global fatigue and improve 4-km cycling time trial (TT4km) performance. After a preliminary session, cyclists (n = 9) performed a TT4km after a CHO or placebo (PLA) mouth rinse. Mean power output, time, and ratings of perceived exertion (RPE) were recorded throughout the TT4km. Twitch interpolation responses (%VA; voluntary activation and ?Tw; delta peak twitch torque) were compared pre and post TT4km with traditional statistics and effect size (ES) analysis. Time-to-complete the 4 km and mean power output were comparable between CHO (386.4 ± 28.0 s) and PLA (385.4 ± 22.4 s). A lower central (p = 0.054) and peripheral (p = 0.02) fatigue in CHO than in PLA were suggested by an extremely-large ES in %VA (manipulation main effect: p = 0.052, d = 1.18; manipulation-by-time interaction effect: p = 0.08, d = 1.00) and an extremely, very-large ES in ?Tw (manipulation main effect: p = 0.07, d = 0.97; time-by-manipulation interaction effect: p = 0.09, d = 0.89). The RPE increased slower in CHO than in PLA (p = 0.051; d = 0.7). The apparent reduction in global fatigue (central and peripheral) and RPESLOPE with only one CHO mouth rinse were not translated into improved TT4km performance. Further tests may be required to verify if these likely differences in global fatigue might represent an edge in the short-lasting cycling time trial performance.
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Project description:Transcranial direct current stimulation (tDCS) is a brain stimulation technique that can enhance motor activity by stimulating the motor path. Thus, tDCS has the potential of improving the performance of brain-computer interfaces during motor neurorehabilitation. tDCS effects depend on several aspects, including the current density, which usually varies between 0.02 and 0.08 mA/cm2, and the location of the stimulation electrodes. Hence, testing tDCS montages at several current levels would allow the selection of current parameters for improving stimulation outcomes and the comparison of montages. In a previous study, we found that cortico-cerebellar tDCS shows potential of enhancing right-hand motor imagery. In this paper, we aim to evaluate the effects of the focal stimulation of the motor cortex over motor imagery. In particular, the effect of supplying tDCS with a 4 × 1 ring montage, which consists in placing an anode on the motor cortex and four cathodes around it, over motor imagery was assessed with different current densities. Electroencephalographic (EEG) classification into rest or right-hand/feet motor imagery was evaluated on five healthy subjects for two stimulation schemes: applying tDCS for 10 min on the (1) right-hand or (2) feet motor cortex before EEG recording. Accuracy differences related to the tDCS intensity, as well as μ and β band power changes, were tested for each subject and tDCS modality. In addition, a simulation of the electric field induced by the montage was used to describe its effect on the brain. Results show no improvement trends on classification for the evaluated currents, which is in accordance with the observation of variable EEG band power results despite the focused stimulation. The lack of effects is probably related to the underestimation of the current intensity required to apply a particular current density for small electrodes and the relatively short inter-electrode distance. Hence, higher current intensities should be evaluated in the future for this montage.
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Project description:BackgroundThe relative timing of transcranial direct current stimulation (tDCS) and motor practice holds potential importance in modulating cortical activity and facilitating behavioral performance.MethodA single-blind, randomized, cross-over experiment was conducted. Twenty healthy participants engaged in a sequential finger-tapping task with their left hand. High-definition anodal tDCS (1 mA, 20 min) was administered over the right primary motor cortex (M1) either during (concurrent-tDCS) or before the motor practice (prior-tDCS). A sham tDCS condition was also employed. The three tDCS conditions were separated by one-week intervals. Cortical hemodynamic activity in the prefrontal cortex (PFC), supplementary motor area (SMA), and M1 measured by functional near-infrared spectroscopy, as well as motor performance assessed by number of correct sequences were examined before (T1), immediately after (T2), and 24 h after the practice (T3). The data was subjected to a two-way repeated measures analysis of variance.ResultsNo significant interaction or main effect of condition were found on motor performance. Regarding cortical hemodynamic activity, none of the regions of interest or channels exhibited a significant interaction effect or main effect of condition. No significant correlation between cortical activity and motor performance was found.ConclusionOur results cannot support the timing effect of single-session anodal tDCS on facilitating brain activity or improving motor performance. These results contribute to the growing body of evidence challenging the efficacy of a single session of exogenous stimulation as an adjunct to motor practice for promoting motor acquisition. Further research should explore alternative tDCS parameters, multiple sessions and various age groups.
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