Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics.

Background: The pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke. Methods: We sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group). Results: It was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924-0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966-1) which can be employed to effectively discriminate MM patients from control. Conclusion: Overall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.

Grip training improves handgrip strength, cognition, and brain white matter in minor acute ischemic stroke patients.

OBJECTIVE: A large proportion of stroke patients experience cognitive impairment. Previous studies found that handgrip training can improve cognitive dysfunction after stroke through an unknown mechanism. In this study, we aimed to examine the influence of handgrip training on the cognition of patients with acute mild ischemic stroke and explore the mechanism using an advanced post-processing method for magnetic resonance imaging. METHODS: Seventy-six patients with acute mild ischemic stroke were recruited for this study and randomly divided into a grip training group (n = 37) and a control group (n = 39). Both groups of patients also received standardized treatment for stroke in the acute phase and for secondary prevention, as well as conventional physical therapy after stroke. Grip strength, global cognitive function, and the local and global efficiencies of white matter networks derived from diffusion tensor images were measured before and after the 12-week training period. RESULTS: In the within-group comparisons, grip training significantly improved the grip strength (3.52 [3.09-3.96], p = 0.02), Montreal Cognitive Assessment (MoCA) (2.27 [1.68-2.86], p = 0.05), and local, but not global, efficiency of the brain white matter network (0.03 [0.02-0.03], p = 0.02) in the experimental group. In contrast, these parameters were not statistically different over the same period in the control group. In the between-groups comparisons, the improvement of grip strength (2.71 [2.20-3.21], p = 0.01), MoCA (1.17 [0.39-1.95], p = 0.05), and local efficiency (0.02 [0.01-0.03], p = 0.01) showed statistically significant differences after the intervention, but not the absolute value of them, neither at the base line nor after the intervention. CONCLUSIONS: Our results indicate that grip training can improve cognitive function by increasing the local efficiency of brain white matter connectivity. This suggests that white matter remodeling is a potential physiological mechanism connecting grip training and cognition improvement.

Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus.

The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

Rapid preparation of crystalline colloidal arrays using a strong electric field dialysis.

We present a simple method for rapid preparation of crystalline colloidal arrays (CCAs) by a strong electric field dialysis (SEFD). This method is based on rapid removing of ionic impurities in colloidal suspensions by applying a strong electric field. In a SEFD process, the negatively charged ions in colloidal suspensions are rapidly driven to the anode, the positively charged ones are rapidly driven to the cathode, and the colloidal particles are withheld in the dialysis tube. It was shown that the colloidal particles aggregated on the wall of the dialysis tube could block the SEFD process, which could be overcome by reversing the direction of the electric field. The purified colloidal particles can self-assemble into a crystalline colloidal array, which has an electrostatically stabilized three-dimensional periodic array of colloidal particles with a characteristic lattice spacing that can be varied by dilution. The reflection spectra show distinct peaks due to diffraction from CCAs. Atomic force microscopy (AFM) image illustrates the non-contacted ordering of the colloidal particles in the CCAs embedded in gels. This indicates the formation of high-quality single CCAs. Using a SEFD method, the preparation time of CCAs can be reduced. This new technique will greatly speed up the process of preparing polymerized crystalline colloidal arrays (PCCAs) into real-world application in the analytical field.

Electrical characterization of silicon tips using conducting atomic force microscopy.

The electrical properties of n-doped Si tips have been characterized in conducting atomic force microscopy under various conditions. Si tips with SiO2 layer on them present complex electric properties: which include a larger positive threshold bias, which is different from that of its doped semiconductor material. Silicon tips after removing their SiO2 layer had smaller positive threshold bias; such bias varied with the loading force: smaller loading forces corresponding to larger positive threshold biases, and it remained constant at lower levels for larger loading forces. Humidity of experiments influenced the threshold bias: lower relative humidities (<25%) and larger loading forces were in favor of getting stable threshold bias. The conductance increased remarkably in high relative humidity although it was kept in a narrow range when relative humidity was lower than 40%. Loading force didn't affect the conductance in the examined relative humidity conditions. One advantage of bare silicon tips over commercial conducting ones is that they smaller radius than gold-coated tips; this is in more favor of reaching single molecular electronics.