Cortical Excitability by Transcranial Magnetic Stimulation as Biomarkers for Seizure Controllability in Temporal Lobe Epilepsy.

OBJECTIVE: To investigate whether indicators of cortical excitability are good biomarkers of seizure controllability in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Three groups of subjects were recruited: those with poorly controlled (PC) TLE (N = 41), well-controlled (WC) TLE (N = 71), and healthy controls (N = 44). Short- and long-latency recovery curves were obtained by paired-pulse transcranial magnetic stimulation. Linear mixed effect models were used to study the effects of group, interstimulus interval (ISI), and antiepileptic drugs on long-interval intracortical inhibition (LICI) and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). RESULTS: The mixed effect model that did not incorporate antiepileptic drugs showed that group and ISI were significant factors for LICI and SICI/ICF. LICI in the healthy control group was greater than in the two epilepsy groups, and the difference was significant at ISIs of 50, 150, and 200 msec. In contrast, SICI/ICF in the PC group was greater than in the healthy control and WC groups, and the difference was significant at an ISI of 15 msec. However, due to large variance, it was difficult to identify a cutoff value with both good sensitivity and good specificity. Incorporating the information of antiepileptic drugs to the mixed effect model did not change the overall results. CONCLUSIONS: Although LICI and SICI/ICF parameters were significantly different at the group level, they may not be suitable biomarkers for the controllability of TLE at the subject level.

The distinct and potentially conflicting effects of tDCS and tRNS on brain connectivity, cortical inhibition, and visuospatial memory.

Noninvasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), are emerging as promising tools for enhancing cognitive functions by modulating brain activity and enhancing cognitive functions. Despite their potential, the specific and combined effects of tDCS and tRNS on brain functions, especially regarding functional connectivity, cortical inhibition, and memory performance, are not well-understood. This study aims to explore the distinct and combined impacts of tDCS and tRNS on these neural and cognitive parameters. Using a within-subject design, ten participants underwent four stimulation conditions: sham, tDCS, tRNS, and combined tDCS + tRNS. We assessed the impact on resting-state functional connectivity, cortical inhibition via Cortical Silent Period (CSP), and visuospatial memory performance using the Corsi Block-tapping Test (CBT). Our results indicate that while tDCS appears to induce brain lateralization, tRNS has more generalized and dispersive effects. Interestingly, the combined application of tDCS and tRNS did not amplify these effects but rather suggested a non-synergistic interaction, possibly due to divergent mechanistic pathways, as observed across fMRI, CSP, and CBT measures. These findings illuminate the complex interplay between tDCS and tRNS, highlighting their non-additive effects when used concurrently and underscoring the necessity for further research to optimize their application for cognitive enhancement.

The influences of inter-trial interval on the thermal and thermal pain thresholds in quantitative sensory testing.

PURPOSE: Thermal threshold and thermal pain threshold determinations are part of quantitative sensory tests. Usually the average of many repeated trials is defined as the threshold. The inter-trial interval (ITI) may have an effect on the later trials. The main purpose of this study was to investigate the influence of ITI on the test results. METHODS: Forty-two healthy subjects were recruited. The limit method was adopted. Each subject received 4 sessions of testing, with one ITI equal to 10, 20, 40 and 60 seconds, respectively. In each session, all four modalities (warm and cold thresholds and cold and hot pain thresholds) were performed. Thermal thresholds were the averages of four trials and thermal pain thresholds were the averages of three trials. The ITI order and the modality order were pseudo-randomized. Analyses of variance were utilized to test the influence of ITI, the modality order and the trial order. RESULTS: The results implied that the test results by the limit method are independent of ITI in the range of 10 to 60 seconds, but the results may not be the true thresholds. CONCLUSION: The results showed that while ITI and the modality order did not have significant effects on the test results, the trial order did have effects on the results of all modalities.

Muscle tone of upper limbs evaluated by quantitative pendulum test in patients with acute cerebellar stroke.

The main objective of this study was to quantify the muscle tone of upper limbs in patients with acute cerebellar stroke. Quantitative pendulum test was conducted, and model analysis was performed. Four parameters (number of swings, relaxation index, stiffness coefficient and damping coefficient) were formulated and the differences between the intact and affected sides were documented. In total, 8 subjects were recruited. While the number of swings, relaxation index and stiffness coefficient showed no difference, damping coefficient on the affected side was significantly smaller than that on the intact side by Wilcoxon signed rank test. The results indicated that the relatively lower muscle tone on the affected side of patients with acute cerebellar stroke was mainly ascribable to the smaller velocity-dependent component.

Application of a stable carbon isotope for identifying Broussonetia papyrifera pollen.

The objective of this study was to investigate whether δ13C values can be used to identify pollen specie in the atmosphere. A Burkard 7-day recording volumetric spore trap was used to collected pollens in the atmosphere in Tainan City, Taiwan, from January 2 to December 28, 2006, and a light microscope was used to identify the pollen species and concentrations. A Burkard cyclone sampler was used to collect particulate matter and an elemental analyzer with an isotope ratio mass spectrometer was used to analyze the δ13C values. Our data showed that the predominate pollen specie in the atmosphere was Broussonetia papyrifera pollen and that the annual average concentration was 27 grains/m3 (pollen season, 36; nonpollen season, 9 grains/m3). The average δ13C value was - 26.19‰ for particulate matter in the atmosphere (pollen season, - 26.00‰; nonpollen season, - 26.28‰). No significant association was observed between δ13C values and Broussonetia papyrifera pollen concentrations. However, the δ13C value in the atmosphere was associated with the levels of Broussonetia papyrifera pollen among the samples with a diameter of particulate matter smaller than 10 µm at a level lower than 40 µg/m3. In addition, the relative contribution of Broussonetia papyrifera pollen to the carbon in the atmosphere using a two end-member mixing models was found to be associated with the Broussonetia papyrifera pollen concentration. In summary, our study suggested that δ13C values can be applied in the assessment of Broussonetia papyrifera pollen specie under specific conditions in the atmosphere.

Composite Polyelectrolyte Multilayer and Mesoporous Bioactive Glass Nanoparticle Coating on 316L Stainless Steel for Controlled Antibiotic Release and Biocompatibility.

Bacterial infection in wounds or implants can cause osteomyelitis, eventually leading to orthopedic implant failure. In this study, polyelectrolyte multilayer (PEM) coating comprising collagen as the cationic layer, chitosan as the barrier layer and γ-poly-glutamic acid as the anionic layer were fabricated onto a 316L stainless steel substrate by spin coating technique. Tetracycline-loaded 57S mesoporous bioactive glass nanoparticles (57S MBG, SiO2:CaO:P2O5 = 57:33:10 by wt%) were introduced into the γ-poly-glutamic acid layers. Herein, 57S MBG nanoparticles were successfully incorporated into the PEMs with a total thickness of ∼53 µm on 316L stainless steel (SS-PEMs-57S), which exhibited good hydrophilicity with a contact angle of 18.71°. The hardness of SS-PEMs-57S was 0.66 GPa while the Young's modulus was 11.5 GPa; these values are similar to those for the cortical bone. The surface roughness of MBG nanoparticle-incorporated PEMs increased from 231 to 384 nm. Controlled release of tetracycline loaded in MBG nanoparticles resulted in sustained antibacterial effect for up to 7 days, with higher release efficacy at low pH, which may be induced by inflammation or infection. Tetracycline loaded in SS-PEMs-57S showed good bacterial inhibition and maintained good cell viability in rat bone marrow mesenchymal stem cells (BMSCs) in the MTT assay. Moreover, SS-PEMs-57S also promoted mineralization of BMSCs. Therefore, this surface modification technology has great potential for endowing orthopedic implants with antibacterial and osteoconductive properties.

Molecular dynamics simulations of the unfolding of the starch binding domain from Aspergillus niger glucoamylase.

The 600 ps molecular dynamics simulations to investigate the unfolding of the starch binding domain from Aspergillus niger glucoamylase were conducted in vacuum as well as in an external field with the dielectric constant of 80 with temperature jump technique. Electrostatic interactions play an important role in determining the stability of the beta-strands in this domain. The starch binding site 1 is less stable than site 2 since it is more exposed to the surface. The disulfide bond between C509 and C604 is unstable since these two residues are located near the flexible linker domain and in the mobile loop region between beta-strands 6 and 7, respectively. The melting temperature, at which the total residual beta-strand content is 50% that of the solution structure, is about 544K for the simulations with dielectric constant of 80, leading to the estimated unfolding timescale of 0.48 ms in vitro. In addition, the unfolding of the starch binding domain is proposed to initiate from the interior region by the lost of the integrity of the secondary structure.

Molecular dynamics simulations of the unfolding mechanism of the catalytic domain from Aspergillus awamori var. X100 glucoamylase.

In this study, 200 ps molecular dynamics simulations were conducted to investigate the unfolding mechanism of the catalytic domain of glucoamylase from Aspergillus awamori var. X100. The unfolding of this domain was suggested to follow a putative hierarchical manner, in which the heavily O-glycosylated belt region from residues T440 to A471 acted as the initiation site, followed by the alpha-helix secondary structure destruction, and then the collapse of the catalytic center pocket. The O-glycosylated belt region surrounded the surface of the catalytic domain in its native state at low temperature, whereas it was extended and is more suitable to be classified as part of the subsequent linker domain at high temperatures due to its high flexibility. The inner set helices of the (alpha/alpha)(6)-barrel seemed to exhibit higher helical content than the outer set ones at all temperatures examined. The distances between the C(alpha) of the three Cys residue pairs fluctuated rapidly at higher temperatures, indicating that these disulfide bonds have little effect on the structural stabilization. The melting temperature, at which the residual total helicity of the catalytic domain is 50%, is much lower than the critical temperature, at which the catalytic center pocket has lost its structural integrity.

Predicted unfolding order of the 13 alpha-helices in the catalytic domain of glucoamylase from Aspergillus awamori var. X100 by molecular dynamics simulations.

The unfolding mechanism of the 13 alpha-helices in the catalytic domain of Aspergillus awamori var. X100 glucoamylase was investigated by 200 ps molecular dynamics simulations in explicit water with temperature jump technique. Rather than a simultaneous event, the unfolding of these 13 alpha-helices followed a random ordered mechanism as alpha8-->alpha1-->alpha11-->alpha7-->alpha10-->alpha3-->alpha12-->alpha13-->alpha4-->alpha5-->alpha9-->alpha6-->alpha2. No significant relationships were found between the unfolding order and the length and the hydrophobicity of the helix. alpha-Helix 8 located in the inner region of the catalytic domain was predicted to be the first helix to unfold, indicating that the destruction of the secondary structure motif was initiated from the inner region of the catalytic domain. The dynamic behavior of these alpha-helices induced by increased kinetic energy during the unfolding process is considered to be similar to the expansion and compression of a series of springs under the influence of mechanical stress.

Power spectral analyses of index finger skin blood perfusion in carpal tunnel syndrome and diabetic polyneuropathy.

The main purpose of this study was to investigate the applicability of frequency domain analysis on laser Doppler flowmetry (LDF) data recorded from the index fingers of patients with carpal tunnel syndrome (CTS) and diabetic polyneuropathy (DPN). Patients with numbness of the palm were recruited and grouped according to the results of electrophysiological examinations into 2×2 groups by the existence or nonexistence of CTS and/or DPN. Skin blood perfusion was recorded by LDF in both the neutral position and the maximally flexed position (the Phalen test). S-transformation was utilized to decompose the recorded data into frequency bands, and the relative band power and power dispersion were calculated. Analysis of variance was used to test the effects of DPN, CTS, and the Phalen test results. The results showed that (1) DPN decreased the absolute power and the relative power in some frequency bands in both positions and CTS increased the power dispersion of some frequency bands only during the Phalen test and (2) there was no difference in the LDF results between patients with positive or negative Phalen test results.

Influence of age on thermal thresholds, thermal pain thresholds, and reaction time.

The main goals of this study were to investigate the effect of age on thermal and thermal pain thresholds and reaction time, and to analyze the influence of age-related changes in reaction time on thermal and thermal pain thresholds. Thermal thresholds (warm/cold) and thermal pain thresholds (hot/cold) were evaluated by the method of limits. Visual reaction time was evaluated in a similar way by a customized computer program. In total, 274 normal subjects (23-87 years old) were recruited. Thermal thresholds, thermal pain thresholds, and reaction time were all related to age. While warm and cold thresholds and cold pain thresholds increased with age, hot pain thresholds decreased with age. The age-related change in reaction time was insufficient to explain the age-related changes in thermal and thermal pain thresholds. In conclusion, age affects thermal and thermal pain thresholds independently of reaction time.

Protein engineering to improve the thermostability of glucoamylase from Aspergillus awamori based on molecular dynamics simulations.

Twelve mutations were constructed to improve the thermostability of glucoamylase from Aspergillus awamori based on the results of molecular dynamics simulations. The thermal unfolding of the catalytic domain followed a putative hierarchical behavior. In addition, the unfolding of the 13 alpha-helices obeyed the random ordered mechanism, in which the alpha-helices 8, 1 and 11 unfolded more rapidly than the others. The catalytic center was well protected by the (alpha/alpha)(6)-barrel at simulation temperatures up to 600 K, whereas the catalytic base, E400, migrated from its original interior pocket to the surface of the catalytic domain by surmounting the hydrophobic barrier provided by alpha-helices 12 and 13 at 800 K. The disulfide bonds engineered to 'lock' the alpha-helix 11 on the surface of the catalytic domain dramatically increased the thermostability. Substituting G396 and G407 with Ala residues slightly increased the thermostability, whereas their specific activity and catalytic efficiency were reduced. This indicates that the introduced residues with higher hydrophobicity were favorable in the loop between alpha-helices 12 and 13, whereas they partially destroyed the hydrogen bond and salt linkage network in the catalytic center. Alpha-helices 12 and 13 can be stabilized by introducing residues with higher hydrophobicity, except for the H391M mutation.