To assess safety and effects of five C-tDCS (charge density 342,857C/m2) delivered at increasing time intervals in 25h.
Safety was defined as absence of serious adverse events and by magnetic ...resonance imaging and spectroscopy. Effects on motor cortex excitability were evaluated by motor evoked potential (MEP) amplitudes. Inter-individual MEP variability was calculated by the SEM at baseline and subjects were classified on the basis of the ratio between normalized MEPs after the first stimulation compared to baseline.
Thirty-two healthy subjects were enrolled. No serious adverse events occurred. Magnetic resonance imaging and spectroscopy did not show structural and biochemical alterations. Only 56% of subjects responded to cathodal-tDCS with the expected reduction of MEP amplitude, 25% were non-responders and 19% opposite responders. In responders, MEP suppression was 32% one hour after the first cathodal-tDC, 21% three hours after the second, no longer present four hours after the third and 12h after the fourth cathodal-tDCS. Loss of effect was due to the increasing interval between C-tDCS and not to intervening homeostatic plasticity.
Five C-tDCS in 25h are safe. Interindividual variability on motor cortex excitability and effect duration limited to three hours should be considered in planning therapeutic trials utilizing repeated C-tDCS.
Background and aims
Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to ...both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI.
Methods
Baseline data from an MCI court (
N
= 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale.
Results
After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (
p
= 0.0155,
p
= 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL.
Conclusions
Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.
Testicular cancer is the most frequent cancer in young men. The large majority of patients have a good prognosis, but in a small group of tumors, the current treatments are not effective. Radioiodine ...is routinely used in the treatment of thyroid cancer and is currently investigated as a potential therapeutic tool even for extra-thyroid tumors able to concentrate this radioisotope. Expression of Na(+)/I(-) symporter (NIS (SLC5A5)), the glycoprotein responsible for iodide transport, has been demonstrated in normal testicular tissue. In this study, we analyzed NIS expression in a large series of testicular carcinomas. Our retrospective series included 107 patients operated for testicular tumors: 98 typical seminomas, six embryonal carcinomas, one mixed embryonal choriocarcinoma, and two Leydig cells tumors. Expression and regulation of NIS mRNA and protein levels were also investigated in human embryonal testicular carcinoma cells (NTERA) by real-time RT-PCR and western blotting respectively. Immunohistochemical analysis showed the presence of NIS in the large majority of seminomas (90/98) and embryonal carcinomas (5/7) of the testis but not in Leydig cell carcinomas. Expression of NIS protein was significantly associated with lymphovascular invasion. In NTERA cells treated with the histone deacetylase inhibitors SAHA and valproic acid, a significant increase in NIS mRNA (about 60- and 30-fold vs control, P<0.001 and P<0.01 respectively) and protein levels, resulting in enhanced ability to uptake radioiodine, was observed. Finally, NIS expression in testicular tumors with the more aggressive behavior is of interest for the potential use of targeting NIS to deliver radioiodine in malignant cells.
The 6-min walk test (6MWT) is a common means of functional assessment. Its relationship to disability-free survival (DFS) is uncertain.
This sub-study of the Measurement of Exercise Tolerance for ...Surgery study had co-primary outcome measures: correlation of the preoperative 6MWT distance with 30 day quality of recovery (15-item quality of recovery) and 12 month WHO Disability Assessment Schedule scores. The prognostic utility of the 6MWT and other risk assessment tools for 12 month DFS was assessed with logistic regression and receiver-operating-characteristic-curve analysis.
Of 574 patients recruited, 567 (99%) completed the 6MWT. Twelve months after surgery, 16 (2.9%) patients had died and 444 (77%) had DFS. The 6MWT correlated weakly with 30 day 15-item quality of recovery (ρ=0.14; P=0.001) and 12 month WHO Disability Assessment Schedule (ρ=–0.23; P<0.0005) scores. When the cohort was split into 6MWT distance tertiles, the adjusted odds ratio of low vs high tertiles for DFS was 3.13 95% confidence interval (CI): 1.54–6.35. The only independent variable predictive of DFS was the Duke Activity Status Index (DASI) score (adjusted odds ratio: 1.06; P<0.0005). The area under the receiver-operating-characteristic curve for DFS was 0.63 (95% CI: 0.57–0.70) for the 6MWT, 0.60 (95% CI: 0.53–0.67) for cardiopulmonary-exercise-testing-derived peak oxygen consumption, and 0.70 (95% CI: 0.64–0.76) for the DASI score.
Of the risk assessment tools analysed, the DASI was the most predictive of DFS. The 6MWT was safe and comparable with cardiopulmonary exercise testing for all predictive assessments. Future research should aim to determine the optimal 6MWT distance thresholds for risk prediction.
Purpose
The aim of this prospective study was to determine the feasibility in terms of repeatability and reproducibility of diffusional kurtosis imaging (DKI) for microstructural assessment of the ...normal cervical spinal cord (cSC) using a phase-sensitive inversion recovery (PSIR) sequence as the anatomical reference for accurately defining white-matter (WM) and gray-matter (GM) regions of interests (ROIs).
Methods
Thirteen young healthy subjects were enrolled to undergo DKI and PSIR sequences in the cSC. The repeatability and reproducibility of kurtosis metrics and fractional anisotropy (FA) were calculated in GM, WM, and cerebral-spinal-fluid (CSF) ROIs drawn by two independent readers on PSIR images of three different levels (C1–C4). The presence of statistically significant differences in DKI metrics for levels, ROIs (GM, WM, and CSF) repeatability, reproducibility, and inter-reader agreement was evaluated.
Results
Intra-class correlation coefficients between the two readers ranged from good to excellent (0.75 to 0.90). The inferior level consistently had the highest concordance. The lower values of scan–rescan variability for all DKI parameters were found for the inferior level. Statistically significant differences in kurtosis values were not found in the lateral white-matter bundles of the spinal cord.
Conclusion
The integration of DKI and PSIR sequences in a clinical MR acquisition to explore the regional microstructure of the cSC in healthy subjects is feasible, and the results obtainable are reproducible. Further investigation will be required to verify the possibility to translate this method to a clinical setting to study patients with SC involvement especially in the absence of MRI abnormalities on standard sequences.
•We studied the effects of tapentadol on CGRP release from isolated rat brainstem.•Tapentadol did not modify CGRP release in basal condition.•Tapentadol inhibited both K+- and capsaicin-evoked CGRP ...release.•The effects of tapentadol were compared to those morphine and reboxetine.•Tapentadol fully mimicked the effects of reboxetine in this paradigm.
We have previously developed an in vitro model of rat brainstem explants. The latter release sizable amounts of calcitonin gene-related peptide (CGRP); basal release can be stimulated by such secretagogues as high KCl concentrations, veratridine or capsaicine. In this paradigm we investigated the activity of the analgesic agent tapentadol; the effects of tapentadol were compared to those of a classical opioid receptor agonist, morphine, and the selective noradrenaline reuptake inhibitor reboxetine. Morphine inhibited basal CGRP release, with statistical significance from 1nM onward and maximal (−44%) inhibition at 100μM. Morphine also inhibited K+-stimulated peptide release, with a significant effect from 1μM and maximal (−39%) decrease at 100μM, but failed to inhibit release stimulated by 10μM capsaicin. At variance, reboxetine had no effect on baseline CGRP outflow, but was able to inhibit both K+-stimulated significant inhibition from 1μM onward and maximal (−37%) decrease at 100μM, and capsaicin-stimulated release significant effect from 1μM and maximal (−31%) decrease at 100μM. Likewise, tapentadol had no effect on baseline CGRP release up to 100μM, but decreased secretion stimulated by 56mM KCl or capsaicin, with significant effects from 0.1 and 1μM respectively; maximal inhibition over 56mM KCl and capsaicin stimuli was −29% and −31%, respectively. Naloxone antagonized the effect of morphine, but not those of reboxetine and tapentadol, on K+-stimulated CGRP secretion. In conclusion the present study provides consistent pharmacological evidence that tapentadol acts as a noradrenaline reuptake inhibitor agent in this experimental model.
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