A Comparative Investigation of Functional Connectivity Utilizing Electroencephalography in Insomnia Patients with and without Restless Leg Syndrome

Objective: The current study aimed to identify distinctive functional brain connectivity characteristics that differentiate patients with restless legs syndrome (RLS) from those with primary insomnia. Methods: Quantitative electroencephalography (QEEG) was employed to analyze connectivity matrices using the phaselocking value technique. A total of 107 patients with RLS (RLS group) and 17 patients with insomnia without RLS (primary insomnia group) were included in the study. Demographic variables were compared using t tests and chi-square tests, while differences in connectivity were examined through multiple analyses of covariance. Correlation analysis was conducted to explore the relationship between connectivity and the severity of RLS. Results: The results indicated significant differences in the primary somatosensory cortex (F = 4.377, r = 0.039), primary visual cortex (F = 4.215, r = 0.042), and anterior prefrontal cortex (F = 5.439, r = 0.021) between the RLS and primary insomnia groups. Furthermore, the connectivity of the sensory cortex, including the primary somatosensory cortex (r = -0.247, p = 0.014), sensory association cortex (r = -0.238, p = 0.028), retrosplenial region (r = -0.302, p = 0.002), angular gyrus (r = -0.258, p = 0.008), supramarginal gyrus (r = -0.230, p = 0.020), primary visual cortex (r = -0.275, p = 0.005) and secondary visual cortex (r = -0.226, p = 0.025) exhibited an inverse association with RLS symptom severity. Conclusion: The prefrontal cortex, primary somatosensory cortex, and visual cortex showed potential as diagnostic biomarkers for distinguishing RLS from primary insomnia. These findings indicate that QEEG-based functional connectivity analysis shows promise as a valuable diagnostic tool for RLS and provides insights into its underlying mechanisms. Further research is needed to explore this aspect further.

An oxygen-insensitive and minimally invasive polymeric microneedle sensor for continuous and wide-range transdermal glucose monitoring.

Despite significant advances in diabetes management, particularly with the introduction of the most recent continuous glucose monitoring devices (CGMDs) that can monitor glucose actively in the transdermal interstitial fluid (ISF) in vivo, CGMDs still have significant disadvantages in terms of accuracy, low interference effect, precision, and stability. This is mostly because they detect hydrogen peroxide at higher potentials and require an oxygen-rich environment. First in its class, we developed an oxygen-insensitive polymeric glucose microneedle (MN) that was functionalized using a new electron-transfer mediator, 3-(3'-phenylimino)-3H-phenothiazinesulfonic acid-based enzyme cocktail for the NAD-GDH system. The inclusion of reduced graphene oxide aided in the absorption of the cocktail via the π-π interaction and enhanced the conductivity and sensor performance. The MN exhibited a dynamic linear range (1-30 mM) with a low detection limit of 26 µM, high sensitivity (18.05 µAmM-1 cm-2), stability (up to 7 days), high selectivity (due to a low oxidation potential of 0.15 V), and a fast response time (∼3 s). In vivo, deployment of the MN in a rabbit model demonstrated that the ISF glucose concentrations measured with the MN for up to 24 h correlate very well with the blood glucose concentrations measured with a commercial glucometer.

Inverted Ion Current Rectification-Based Chemical Delivery Probes for Stimulation of Neurons.

Ion current rectification (ICR), diodelike behavior in surface-charged nanopores, shows promise in the design of delivery probes for manipulation of neural networks as it can solve diffusive leakages that might be critical in clinical and research applications. However, it has not been achieved because ICR has restrictions in nanosized dimension and low electrolyte concentration, and rectification direction is inappropriate for delivery. Herein, we present a polyelectrolyte gel-filled (PGF) micropipette harnessing inverted ICR as a delivery probe, which quantitatively transports glutamate to stimulate primary cultured neurons with high efficiency while minimizing leakages. Since the gel works as an ensemble of numerous surface-charged nanopores, the current is rectified in the micro-opening and physiological environment. By extending the charge-selective region using the gel, inverted ICR is generated, which drives outward deliveries of major charge carriers. This study will help in exploring new aspects of ICR and broaden its applications for advanced chemical delivery.

Mismatch Negativity and Loudness Dependence of Auditory Evoked Potentials among Patients with Major Depressive Disorder, Bipolar II Disorder, and Bipolar I Disorder.

Mismatch negativity (MMN) and loudness dependence of auditory evoked potentials (LDAEP), which are event-related potentials, have been investigated as biomarkers. MMN indicates the pre-attentive function, while LDAEP may be an index of central serotonergic activity. This study aimed to test whether MMN and LDAEP are useful biological markers for distinguishing patients with bipolar disorder (BD) and major depressive disorder (MDD), as well as the relationship between MMN and LDAEP. Fifty-five patients with major depressive episodes, aged 20 to 65 years, who had MDD (n = 17), BD type II (BIID) (n = 27), and BD type I (BID) (n = 11), were included based on medical records. Patients with MDD had a higher MMN amplitude than those with BID. In addition, the MMN amplitude in F4 positively correlated with the Korean version of mood disorder questionnaire scores (r = 0.37, p = 0.014), while the MMN amplitude in F3 correlated negatively with LDAEP (r = -0.30, p = 0.024). The odds ratios for the BID group and some variables were compared with those for the MDD group using multinomial logistic regression analysis. As a result, a significant reduction of MMN amplitude was found under BID diagnosis compared to MDD diagnosis (p = 0.015). This study supported the hypothesis that MMN amplitude differed according to MDD, BIID, and BID, and there was a relationship between MMN amplitude and LDAEP. These findings also suggested that BID patients had a reduced automatic and pre-attentive processing associated with serotonergic activity or N-methyl-D-aspartate receptor.

Amperometric Glucose Biosensor Utilizing Zinc Oxide-chitosan-glucose Oxidase Hybrid Composite Films on Electrodeposited Pt-Fe(III).

We developed an amperometric glucose biosensor based on glucose oxidase (GOx) embedded in zinc oxide (ZnO)-chitosan (CS) hybrid composite films on electrodeposited Pt-Fe(III). This sensor exhibited a fast amperometric response (less than 10 s) to glucose, linearity from 10 µM to 11.0 mM of glucose with a detection limit of 1.0 µM (S/N = 3) and sensitivity of 30.70 µA mM-1 cm-2. An apparent Michaelis-Menten constant of 5.19 mM indicated high affinity between glucose and GOx immobilized in the ZnO-CS films. The effect of interferences such as uric acid, ascorbic acid, and acetaminophen on the performance of this sensor was negligible. In addition, this sensor retained 87% of its initial performance after two weeks of storage at 4°C, indicating that the hybrid composite films allowed successful immobilization of GOx with its high enzymatic activity.

Immediate effects of scapular stabilizing exercise in chronic stroke patient with winging and elevated scapula: a case study.

[Purpose] The purpose of this study was to investigate the effect of scapular stabilizing exercise in a stroke patient with winging and elevated scapula. [Subject and Methods] The subject was a 46-year-old female with a history of stroke. She had right side hemiplegia with winging and elevated scapula on the right side, and had compensatory motions of the neck and shoulder when using the paretic upper extremity. The subject participated in scapular stabilizing exercises for four days. This exercise program consisted of scapular protraction-retraction in an upright seated position. Scapular position was measured as distance between scapular medial border and thoracic vertebrae 3, 4. Upper extremity function was measured as time required for lifting and lowering a cup with the affected arm. [Results] After intervention, distance between scapular medial border and spinouse process of T3, 4 decreased. Time required for lifting and lowering a cup with the affected arm decreased. Compensatory motions of the neck and shoulder joint decreased. [Conclusion] Despite the short period, scapular stabilizing exercises had a positive effect on scapular position and upper extremity function.

Photoelectrochemical and Impedance Spectroscopic Analysis of Amorphous Si for Light-Guided Electrodeposition and Hydrogen Evolution Reaction.

For more efficient photoelectrochemical water splitting, there is a dilemma that a photoelectrode needs both light absorption and electrocatalytic faradaic reaction. One of the promising strategies is to deposit a pattern of electrocatalysts onto a semiconductor surface, leaving sufficient bare surface for light absorption while minimizing concentration overpotential as well as resistive loss at the ultramicroelectrodes for faradaic reaction. This scheme can be successfully realized by "maskless" direct photoelectrochemical patterning of electrocatalyst onto an SiOx/amorphous Si (a-Si) surface by the light-guided electrodeposition technique. Electrochemical impedance spectroscopy at various pHs tells us much about how it works. The surface states at the SiOx/a-Si interface can mediate the photogenerated electrons for hydrogen evolution, whereas electroactive species in the solution undergo outer-sphere electron transfer, taking electrons tunneling across the SiOx layer from the conduction band. In addition to previously reported long-distance lateral electron transport behavior at a patterned catalyst/SiOx/a-Si interface, the charging process of the surface states plays a crucial role in proton reduction, leading to deeper understanding of the operation mechanisms for photoelectrochemical water splitting.

Nanoscale Electrocatalysis of Hydrazine Electro-Oxidation at Blistered Graphite Electrodes.

There is great interest in finding and developing new, efficient, and more active electrocatalytic materials. Surface modification of highly oriented pyrolytic graphite, through the introduction of surface "blisters", is demonstrated to result in an electrode material with greatly enhanced electrochemical activity. The increased electrochemical activity of these blisters, which are produced by electro-oxidation in HClO4, is revealed through the use of scanning electrochemical cell microscopy (SECCM), coupled with complementary techniques (optical microscopy, field emission-scanning electron microscopy, Raman spectroscopy, and atomic force microscopy). The use of a linear sweep voltammetry (LSV)-SECCM scan regime allows for dynamic electrochemical mapping, where a voltammogram is produced at each pixel, from which movies consisting of spatial electrochemical currents, at a series of applied potentials, are produced. The measurements reveal significantly enhanced electrocatalytic activity at blisters when compared to the basal planes, with a significant cathodic shift in the onset potential of the hydrazine electro-oxidation reaction. The improved electrochemical activity of the hollow structure of blistered graphite could be explained by the increased adsorption of protonated hydrazine at oxygenated defect sites, the ease of ion-solvent intercalation/deintercalation, and the reduced susceptibility to N2 nanobubble attachment (as a product of the reaction). This study highlights the capability of electrochemistry to tailor the surface structure of graphite and presents a new electrocatalyst for hydrazine electro-oxidation.

Impact of Surface Chemistry on Nanoparticle-Electrode Interactions in the Electrochemical Detection of Nanoparticle Collisions.

The electrochemical detection of a single nanoparticle (NP) at a support electrode can provide key information on surface chemistry and fundamental electron transfer (ET) properties at the nanoscale. This study employs scanning electrochemical cell microscopy (SECCM) as a fluidic device to both deliver individual citrate-capped gold nanoparticles (AuNPs) and study the interactions between them and a range of alkanethiol-modified Au electrodes with different terminal groups, namely, -COOH, -OH, and -CH3. Single NP collisions were detected through the AuNP-mediated ET reaction of Fe(CN)6(4-/3-) in aqueous solution. The collision frequency, residence time, and current-time characteristics of AuNPs are greatly affected by the terminal groups of the alkanethiol. Methods to determine these parameters, including the effect of the instrument response function, and derive ET kinetics are outlined. To further understand the interactions of AuNPs with these surfaces, atomic force microscopy (AFM) force measurements were performed using citrate-modified Au-coated AFM tips and the same alkanethiol-modified Au substrates in aqueous solution at the same potential bias as for the AuNP collision experiments. Force curves on OH-terminated surfaces showed no repulsion and negligible adhesion force. In contrast, a clear repulsion (on approach) was seen for COOH-terminated surface and adhesion forces (on retract) were observed for both COOH- and CH3-terminated surfaces. These interactions help to explain the residence times and collision frequencies in AuNP collisions. More generally, as the interfacial properties probed by AFM appear to be amplified in NP collision experiments, and new features also become evident, it is suggested that such experiments provide a new means of probing surface chemistry at the nanoscale.

Time-Resolved Detection and Analysis of Single Nanoparticle Electrocatalytic Impacts.

There is considerable interest in understanding the interaction and activity of single entities, such as (electro)catalytic nanoparticles (NPs), with (electrode) surfaces. Through the use of a high bandwidth, high signal/noise measurement system, NP impacts on an electrode surface are detected and analyzed in unprecedented detail, revealing considerable new mechanistic information on the process. Taking the electrocatalytic oxidation of H2O2 at ruthenium oxide (RuOx) NPs as an example, the rise time of current-time transients for NP impacts is consistent with a hydrodynamic trapping model for the arrival of a NP with a distance-dependent NP diffusion-coefficient. NP release from the electrode appears to be aided by propulsion from the electrocatalytic reaction at the NP. High-frequency NP impacts, orders of magnitude larger than can be accounted for by a single pass diffusive flux of NPs, are observed that indicate the repetitive trapping and release of an individual NP that has not been previously recognized. The experiments and models described could readily be applied to other systems and serve as a powerful platform for detailed analysis of NP impacts.

Redox-dependent spatially resolved electrochemistry at graphene and graphite step edges.

The electrochemical (EC) behavior of mechanically exfoliated graphene and highly oriented pyrolytic graphite (HOPG) is studied at high spatial resolution in aqueous solutions using Ru(NH3)6(3+/2+) as a redox probe whose standard potential sits close to the intrinsic Fermi level of graphene and graphite. When scanning electrochemical cell microscopy (SECCM) data are coupled with that from complementary techniques (AFM, micro-Raman) applied to the same sample area, different time-dependent EC activity between the basal planes and step edges is revealed. In contrast, other redox couples (ferrocene derivatives) whose potential is further removed from the intrinsic Fermi level of graphene and graphite show uniform and high activity (close to diffusion-control). Macroscopic voltammetric measurements in different environments reveal that the time-dependent behavior after HOPG cleavage, peculiar to Ru(NH3)6(3+/2+), is not associated particularly with any surface contaminants but is reasonably attributed to the spontaneous delamination of the HOPG with time to create partially coupled graphene layers, further supported by conductive AFM measurements. This process has a major impact on the density of states of graphene and graphite edges, particularly at the intrinsic Fermi level to which Ru(NH3)6(3+/2+) is most sensitive. Through the use of an improved voltammetric mode of SECCM, we produce movies of potential-resolved and spatially resolved HOPG activity, revealing how enhanced activity at step edges is a subtle effect for Ru(NH3)6(3+/2+). These latter studies allow us to propose a microscopic model to interpret the EC response of graphene (basal plane and edges) and aged HOPG considering the nontrivial electronic band structure.

Six-month functional recovery of stroke patients: a multi-time-point study.

The aim of this study is to compare the time-course changes in neurologic impairments (trunk control, motor function, sensory, and cognition) and recovery in functional impairments (activity of daily livings and gait) simultaneously from initiating rehabilitation to 6 months after stroke. Consecutive stroke patients were recruited from the department of nervous surgery, and transferred into the department of rehabilitation medicine and continued on treatment during the acute stage. Outcome measures were examined at the initial rehabilitation baseline, 1, 2, and 4 weeks after rehabilitation treatment, and 3, 4, 5, and 6 months after stroke. Patients were assessed using the Trunk Impairment Scale, the Fugl-Meyer Motor and Sensory Assessments for the upper and lower limbs, Mini-Mental State Examination, Functional Ambulation Category, and Modified Barthel Index. Twenty consecutive patients were analyzed in the study with complete assessments. The recovery was relatively rapid during the 4 weeks after treatment (P value ranges from <0.001 to <0.007) and then to a lesser extent decelerated between 3 and 6 months after stroke (P value between <0.001 and 0.080). Statistical comparison by repeated measures analysis showed a significant interaction between time points and measures of all recovery variables (P<0.001). Significant differences in level of impairments and functional recovery were found at the different time points. In comparison with the lower leg and trunk control, the upper arm showed less recovery, with a significant difference. All variables except for leg motor function improved continuously over 6 months after stroke. Nevertheless, this study confirms the importance of the period within 3 months for recovery after stroke, during which most of the recovery occurred, ranging from 48 to 91%. Therefore, intensive treatment targeting motor and sensory functions early after stroke may be beneficial for recovery of impairments and functional performance.

The effect of various dual task training methods with gait on the balance and gait of patients with chronic stroke.

[Purpose] This study examined the effects of various dual task gait training methods (motor dual task gait training, cognitive dual task gait training, and motor and cognitive dual task gait training) on the balance and gait abilities of chronic stroke patients. [Subjects and Methods] Thirty-three outpatients performed dual task gait training for 30 minutes per day, three times a week, for eight weeks from June to August, 2012. Balance ability was measured pre-and posttest using the stability test index, the weight distribution index, the functional reach test, the timed up and go test, and the four square step test. Gait ability was measured by the 10 m walk test and a 6 min walk test before and after the training. The paired t-test was used to compare measurements before and after training within each group, and ANOVA was used to compare measurements before and after training among the groups. [Results] Comparisons within each group indicated significant differences in all variables between before and after the training in all three groups. Comparison between the groups showed that the greatest improvements were seen in all tests, except for the timed up and go test, following motor and cognitive dual task gait training. [Conclusion] In a real walking environment, the motor and cognitive dual task gait training was more effective at improving the balance and gait abilities of chronic stroke patients than either the motor dual task gait training or the cognitive dual task gait training alone.

Electrochemical signal amplification for immunosensor based on 3D interdigitated array electrodes.

We devised an electrochemical redox cycling based on three-dimensional interdigitated array (3D IDA) electrodes for signal amplification to enhance the sensitivity of chip-based immunosensors. The 3D IDA consists of two closely spaced parallel indium tin oxide (ITO) electrodes that are positioned not only on the bottom but also the ceiling, facing each other along a microfluidic channel. We investigated the signal intensities from various geometric configurations: Open-2D IDA, Closed-2D IDA, and 3D IDA through electrochemical experiments and finite-element simulations. The 3D IDA among the four different systems exhibited the greatest signal amplification resulting from efficient redox cycling of electroactive species confined in the microchannel so that the faradaic current was augmented by a factor of ∼100. We exploited the enhanced sensitivity of the 3D IDA to build up a chronocoulometric immunosensing platform based on the sandwich enzyme-linked immunosorbent assay (ELISA) protocol. The mouse IgGs on the 3D IDA showed much lower detection limits than on the Closed-2D IDA. The detection limit for mouse IgG measured using the 3D IDA was ∼10 fg/mL, while it was ∼100 fg/mL for the Closed-2D IDA. Moreover, the proposed immunosensor system with the 3D IDA successfully worked for clinical analysis as shown by the sensitive detection of cardiac troponin I in human serum down to 100 fg/mL.

Modulation of quinone PCET reaction by Ca2+ ion captured by calix[4]quinone in water.

Calix[4]arene-triacid-monoquinone (CTAQ), a quinone-containing water-soluble ionophore, was utilized to investigate how proton-coupled electron transfer (PCET) reactions of quinones were influenced by redox-inactive metal ions in aqueous environment. This ionophoric quinone derivative captured a Ca(2+) ion that drastically altered the voltammetric behavior of quinone, showing a characteristic response to pH and unique redox wave separation. Spectroelectrochemistry verified significant stabilization of the semiquinone, and electrocatalytic currents were observed in the presence of Ca(2+)-free CTAQ. Using digital simulation of cyclic voltammograms to clarify how the thermodynamic properties of quinones were altered, a simple scheme was proposed that successfully accounted for all the observations. The change induced by Ca(2+) complexation was explained on the basis of the combined effects of the electrostatic influence of the captured metal ion and hydrogen bonding of water molecules with the support of DFT calculation.

Enhanced electrochemical reactions of 1,4-benzoquinone at nanoporous electrodes.

We report that the proton-coupled electron transfer kinetics of 1,4-benzoquinone was significantly enhanced in electrified nanopores in aqueous media. At nanoporous Pt and Au electrodes, the voltammetric behaviour of 1,4-benzoquinone at nanoporous electrodes was clearly distinct from that at flat surfaces. Proton transfer as well as electron transfer kinetics were facilitated in the nanopores by the confinement effect, which indicates all factors originated from the geometric features of nano-scale concave space surrounded by inner walls, suggesting how to utilize nanoporous electrodes for electrocatalysis.

Graphene-incorporated chitosan substrata for adhesion and differentiation of human mesenchymal stem cells.

A simple method that uses graphene to fabricate nanotopographic substrata was reported for stem cell engineering. Graphene-incorporated chitosan substrata promoted adhesion and differentiation of human mesenchymal stem cells (hMSCs). In addition, we proposed that nanotopographic cues of the substrata could enhance cell-cell and cell-material interactions for promoting functions of hMSCs.

A BODIPY-functionalized bimetallic probe for sensitive and selective color-fluorometric chemosensing of Hg2+.

A new BODIPY dye conjugate has demonstrated selective quenching by mercury over other metal ions. Coupling of this probe to Au-Fe(3)O(4) nanoparticles as well as platinum electrodes offered sensitive systems for suspension and surface based sensing, respectively.

Charged nanomatrices as efficient platforms for modulating cell adhesion and shape.

In this article, we describe the design and manipulation of charged nanomatrices and their application as efficient platforms for modulating cell behaviors. Using electrospraying technology and well designed biomaterials, poly(ɛ-caprolactone; PCL) and polyethylenimine, the negatively charged PCL nanomatrix (nPCL nanomatrix) and the positively charged PCL nanomatrix (pPCL nanomatrix) were fabricated. It was demonstrated that cell adhesion, affinity, and shape were sensitively modulated in negatively and positively charged nanomatrices. Our results showed that the pPCL nanomatrix promoted adhesion of NIH 3T3 fibroblast cells as compared to the nPCL nanomatrix. When fluid shear stress was applied, cell affinity on the pPCL nanomatrix increased even more. NIH 3T3 fibroblast cells adopted a relatively spherical shape on the pPCL nanomatrix while adopting an aligned, narrow shape on the nPCL nanomatrix. It was also found that charged nanomatrices influenced the cross-sectional cell shape. The cross-sectional cell shape on the pPCL nanomatrix was extremely flattened, whereas the cross-sectional cell shape was relatively round on the nPCL nanomatrix and some of the adhered cells floated. We also showed that the surfaces of the nPCL and pPCL nanomatrices adsorbed the different serum proteins. These results collectively demonstrated a combination of environmental factors including nanoscale structure, electrostatic forces, and absorption of biomolecules on charged substrates affected cell response in terms of cellular adhesion and shape.

Gold microshell tip for in situ electrochemical Raman spectroscopy.

Tip fabrication by a new strategy is proposed for simultaneous acquisition of electrochemical (EC) signals from an ultramicroelectrode and spectroscopic information from surface-enhanced Raman scattering (SERS). The EC-SERS tip is prepared by carefully tuning a SERS-active gold microshell to maximize Raman scattering, mechanically attaching it to the end of a micropipet, and electrically connecting it to a ruthenium inner layer through electroless deposition.