Structural connectivity-based predictors of cognitive impairment in stroke patients attributable to aging.

Despite the rising global burden of stroke and its socio-economic implications, the neuroimaging predictors of subsequent cognitive impairment are still poorly understood. We address this issue by studying the relationship of white matter integrity assessed within ten days after stroke and patients' cognitive status one year after the attack. Using diffusion-weighted imaging, we apply the Tract-Based Spatial Statistics analysis and construct individual structural connectivity matrices by employing deterministic tractography. We further quantify the graph-theoretical properties of individual networks. The Tract-Based Spatial Statistic did identify lower fractional anisotropy as a predictor of cognitive status, although this effect was mostly attributable to the age-related white matter integrity decline. We further observed the effect of age propagating into other levels of analysis. Specifically, in the structural connectivity approach we identified pairs of regions significantly correlated with clinical scales, namely memory, attention, and visuospatial functions. However, none of them persisted after the age correction. Finally, the graph-theoretical measures appeared to be more robust towards the effect of age, but still were not sensitive enough to capture a relationship with clinical scales. In conclusion, the effect of age is a dominant confounder especially in older cohorts, and unless appropriately addressed, may falsely drive the results of the predictive modelling.

Spatio-Temporal Gait Parameters in Association with Medications and Risk of Falls in the Elderly.

Purpose: The aim of this study was to analyze factors affecting spatio-temporal gait parameters in elderly people of both genders and different ages with different risks of fall, fall history, and medications. Patients and Methods: A total of 210 community-dwelling older adults (156 females, 54 males; mean age 72.84±6.26 years) participated in this study. To assess the risk of falls, the Downton Fall Risk Index was used. An additional question about medication intake (all prescribed drugs) was asked. To assess the spatio-temporal gait parameters, the Zebris FDM platform was used. Gait parameters and Downton Fall Risk Index, stratified by participants' history of falls, multiple medication use (0/1/2+), gender, age, and medication categories, were statistically analyzed using the Mann-Whitney U-test and Kruskal-Wallis test. Results: When comparing different medication categories, a Downton Fall Risk Index score indicating a high risk of falls was observed in the psychotropic medication category (3.56±1.67). A gait velocity suggesting a higher risk of falls (≤3.60 km/h) was observed in the psychotropic (2.85±1.09 km/h) and diabetes (2.80±0.81 km/h) medication categories, in the age groups 70-79 years (3.30±0.89 km/h) and 80+ years (2.67±0.88 km/h), and in participants using two or more medications (3.04±0.93 km/h). Conclusion: The results of this study confirm previous observations and show that higher age and multiple medication negatively affect the gait, and that the higher risk of falls is associated with psychotropic and diabetes medication use. These results provide important information for future fall preventive programs for the elderly that would be especially beneficial for elderly people taking psychotropic and diabetes medication.

Dance Intervention Impact on Brain Plasticity: A Randomized 6-Month fMRI Study in Non-expert Older Adults.

Background: Dance is a complex activity combining physical exercise with cognitive, social, and artistic stimulation. Objectives: We aimed to assess the effects of dance intervention (DI) on intra and inter-network resting-state functional connectivity (rs-FC) and its association to cognitive changes in a group of non-demented elderly participants. Methods: Participants were randomly assigned into two groups: DI and life as usual (LAU). Six-month-long DI consisted of supervised 60 min lessons three times per week. Resting-state fMRI data were processed using independent component analysis to evaluate the intra and inter-network connectivity of large-scale brain networks. Interaction between group (DI, LAU) and visit (baseline, follow-up) was assessed using ANOVA, and DI-induced changes in rs-FC were correlated with cognitive outcomes. Results: Data were analyzed in 68 participants (DI; n = 36 and LAU; n = 32). A significant behavioral effect was found in the attention domain, with Z scores increasing in the DI group and decreasing in the LAU group (p = 0.017). The DI as compared to LAU led to a significant rs-FC increase of the default mode network (DMN) and specific inter-network pairings, including insulo-opercular and right frontoparietal/frontoparietal control networks (p = 0.019 and p = 0.023), visual and language/DMN networks (p = 0.012 and p = 0.015), and cerebellar and visual/language networks (p = 0.015 and p = 0.003). The crosstalk of the insulo-opercular and right frontoparietal networks were associated with attention/executive domain Z-scores (R = 0.401, p = 0.015, and R = 0.412, p = 0.012). Conclusion: The DI led to intervention-specific complex brain plasticity changes that were of cognitive relevance.

Could the Evaluation of Muscle Strength Imbalances Be Used as a Predictor of Total Hip Arthroplasty?

Loss of muscle strength characterizes the period before total hip arthroplasty (THA). Little is known about whether muscle strength imbalances caused by muscle strength decline could be considered another clinical predictor for THA. This study aimed to determine whether muscle imbalances may be used as a clinical predictor for THA surgery. Thirty-six participants were enrolled in the study. Eighteen patients had THA (THA group), while 18 were healthy elders (CON group). Ipsilateral (H/Q) and bilateral (% Def) muscle imbalances of the knee were assessed. THA patients showed impairment of the extensors on the affected extremity compared to those unaffected. A comparison between the groups proved there were weakened flexors in the THA group on both extremities. A comparison of the imbalances revealed a significant bilateral imbalance of the extensors and ipsilateral imbalance of both extremities in the THA group. We computed two logistic regressions using bilateral and ipsilateral imbalance as the predictors of THA surgery. We found that bilateral extensor imbalance may be used as a predictor for THA (Nagelkerke R2 = 0.22). A decrease of the bilateral extensors imbalance by 8% decreases the probability of THA by 8%. The most interesting finding is that the evaluation of the bilateral extensor imbalance may be used as another clinical predictor for THA.

Ictal gamma-band interactions localize ictogenic nodes of the epileptic network in focal cortical dysplasia.

OBJECTIVE: Epilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis. METHODS: The directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation. RESULTS: Analysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25-170 Hz; p < 0.005) - ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012). CONCLUSION: The prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone. SIGNIFICANCE: Ictogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.

Multishell Diffusion MRI Reflects Improved Physical Fitness Induced by Dance Intervention.

Using multishell diffusion MRI and both tract-based spatial statistics (TBSS) and probabilistic tracking of specific tracts of interest, we evaluated the neural underpinnings of the impact of a six-month dance intervention (DI) on physical fitness and cognitive outcomes in nondemented seniors. The final cohort had 76 nondemented seniors, randomized into DI and control (life as usual) groups. Significant effects were observed between the DI and control groups in physical fitness measures and in attention. We detected associations between improved physical fitness and changes in diffusion tensor imagining (DTI) measures in the whole white matter (WM) skeleton and in the corticospinal tract and the superior longitudinal fascicle despite the fact that no significant differences in changes to the WM microstructure were found between the two groups.

The differences in postural stability between cross-country and Alpine skiers with intellectual disabilities.

PURPOSE: The purpose of this study was to analyse differences in postural stability between athletes with ID competing in Alpine and Cross country (XC) skiing to assess the effect of special sports training on postural stability in persons with ID. METHODS: Athletes with ID were divided into four groups by their discipline: Alpine skiers (n = 9), XC skiers 2.5 to 10 km (n = 10), XC skiers 500 to 1000 m (n = 18) and XC skiers 50 and 100 m (n = 10). All participants were asked to stand barefooted on the Zebris FDM platform (Medical GmbH, Germany) with their eyes open and closed. To compare differences between groups one-way ANOVA with Tukey HSD test was used. To compare the difference between the eyes open and closed, t-test was used. RESULTS: Statistical analysis showed no significant differences between Alpine and XC skiers in analysed variables. The analysis of COP velocity showed superior postural stability in XC skiers 2.5 to 10 km compared to XC skiers 500 and 1000 m. In XC skiers 500 and 1000 m, XC skiers 2.5 to 10 km and Alpine skiers a significant increase in COP velocity was observed when having the eyes closed. In XC skiers 50 and 100 m, no statistically significant differences between the eyes open and closed conditions were observed. CONCLUSIONS: Despite different sports training, no difference between Alpine and XC skiers in postural stability was observed. When comparing XC skiers, better postural stability was observed in skiers running longer distances, suggesting that this sports training enhances balance skills needed in everyday life.

Cognitive effects of dance-movement intervention in a mixed group of seniors are not dependent on hippocampal atrophy.

Dance-movement intervention (DMI) offers multi-component stimulation of cognitive functions, and it may ameliorate cognitive deficits in the elderly. We investigated the effects of intensive DMI on the cognitive performances of healthy seniors (HS) and patients with mild cognitive impairment (MCI). In addition, we evaluated whether the baseline MRI hippocampus-to-cortex volume (HV:CTV) ratio (i.e., a marker of a typical AD-specific brain atrophy and of distribution of neurofibrillary tangles in the brain) has any impact on the DMI-induced cognitive changes. The research cohort consisted of 99 subjects who were randomly assigned (in a 1:1 ratio) to a DMI group or to a control (life-as-usual) group. The DMI group consisted of 49 subjects with an average age of 69.16 years (SD = 5.36), of which 34 were HS (69.4%) and 15 had MCI (30.6%). The control group consisted of 50 subjects aged 68.37 years (SD = 6.10), of which 31 were HC (62%) and 19 (38%) had MCI. The DMI group underwent a 6-month intervention, which consisted of 60 lessons supervised by a qualified instructor. Statistical analysis yielded a significant improvement of the figural fluency task as measured by the five-point test in the DMI group as compared to the control group [t (97) = 2.72; p = 0.008]. The baseline HV:CTV ratio was not associated with cognitive changes on that task or with changes in any cognitive domain's Z scores. We observed DMI-induced effect on the test evaluating executive functions across the spectrum of HS and MCI, which was not dependent on the magnitude of AD-related brain pathology.

Exercise-induced circulating microRNA changes in athletes in various training scenarios.

BACKGROUND: The aim of the study was to compare selected extracellular miRNA levels (miR-16, miR-21, miR-93 and miR-222 with the response to 8-week-long explosive strength training (EXPL), hypertrophic strength training (HYP) and high-intensity interval training (HIIT). METHODS: 30 young male athletes of white European origin (mean age: 22.5 ± 4.06 years) recruited at the Faculty of Sports Studies of Masaryk University were enrolled in this study. The study participants were randomly assigned to three possible training scenarios: EXPL, HYP or HITT and participated in 8-week-long program in given arm. Blood plasma samples were collected at the baseline and at week 5 and 8 and anthropometric and physical activity parameters were measured. Pre- and post-intervention characteristics were compared and participants were further evaluated as responders (RES) or non-responders (NRES). RES/NRES status was established for the following characteristics: 300°/s right leg extension (t300), 60°/s right leg extension (t60), isometric extension (IE), vertical jump, isometric extension of the right leg and body fat percentage (BFP). RESULTS: No differences in miRNA levels were apparent between the intervention groups at baseline. No statistically significant prediction role was observed using crude univariate stepwise regression model analysis where RES/NRES status for t300, t60, IE, vertical jump and pFM was used as a dependent variable and miR-21, miR-222, miR-16 and miR-93 levels at baseline were used as independent variables. The baseline levels of miR-93 expressed an independent prediction role for responder status based on isometric extension of the right leg (beta estimate 0.76, 95% CI: -0.01; 1.53, p = 0.052). DISCUSSION: The results of the study indicate that 8-week-long explosive strength training, hypertrophic strength training and high-intensity interval training regimens are associated with significant changes in miR-16, mir-21, miR-222 and miR-93 levels compared to a baseline in athletic young men.

Different in vitro metabolism of paclitaxel and docetaxel in humans, rats, pigs, and minipigs.

We investigated cytochrome P450 (P450)-catalyzed metabolism of the important cancer drugs paclitaxel and docetaxel in rat, pig, minipig, and human liver microsomes and cDNA-expressed P450 enzymes. In rat microsomes, paclitaxel was metabolized mainly to C3'-hydroxypaclitaxel (C3'-OHP) and to a lesser extent to C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP), and another unknown monohydroxylated paclitaxel. In pig and minipig microsomes, this unknown hydroxypaclitaxel was the main metabolite, whereas C3'-OHP was a minor product. In minipigs, C2-OHP was the next minor product. In human liver microsomes, 6 alpha-hydroxypaclitaxel (6 alpha-OHP) was the main metabolite, followed by C3'-OHP and C2-OHP. Among different cDNA-expressed human P450 enzymes (CYP1A2, 1B1, 2A6, 2C9, 2E1, and 3A4), only CYP3A4 enzyme formed C3'-OHP and C2-OHP. Docetaxel was metabolized in pig, minipig, rat, and human liver microsomes mainly to hydroxydocetaxel (OHDTX), whereas CYP3A-induced rat microsomes produced primarily diastereomeric hydroxyoxazolidinones. Human liver microsomes from 10 different individuals formed OHDTX at different rates correlated with CYP3A4 content. Troleandomycin as a selective inhibitor of CYP3A inhibited the formation of C3'-OHP, C2-OHP, and di-OHP, as well as the unknown OHP produced in rat, minipig, and pig microsomes. In human liver microsomes, troleandomycin inhibited C3'-OHP and C2-OHP formation, and a suitable inhibitor of human CYP2C8, fisetin, strongly inhibited the formation of 6 alpha-OHP, known to be catalyzed by human CYP2C8. In conclusion, the metabolism of docetaxel is the same in all four species, but metabolism of paclitaxel is different, and 6 alpha-OHP remains a uniquely human metabolite. Pigs and minipigs compared with each other formed the same metabolites of paclitaxel.